https://microbewiki.kenyon.edu/api.php?action=feedcontributions&user=Daniel.E.Robinson-1&feedformat=atommicrobewiki - User contributions [en]2024-03-28T08:44:59ZUser contributionsMediaWiki 1.39.6https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91779Rabies2013-07-26T09:42:20Z<p>Daniel.E.Robinson-1: /* Lethal Dose */</p>
<hr />
<div>[[Image:OUA.png|thumb|200px|center|'''' Microbiology in Arezzo.]]<br />
[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as seen among many animals. The disease is known to cause hyperactivity, sporadic behavior, and aggressiveness to things around them. Infected animals and humans eventually succumb to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies and also came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically that phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the virus is extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammatory response can clearly be seen. The same inflammatory response can be seen when using an attenuated form of the wild type virus. [[#References|[6]]]<br />
<br />
=Diagnosis=<br />
[[Image:CDC1_post_mortem.gif|thumb|200px|right|''"Post mortem brain"'' Confirmed case of rabies by the CDC from post mortem testing. The brain weighed 1610g (normal 1300-1400). From: CDC.gov [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5913a3.htm]]]<br />
<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
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(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
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Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[7]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in contact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
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3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
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4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
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5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
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6 Wang Z.W., Sarmento L, Wang Y, Li X-G, Dhingra V, Tseggai T, Jiang B, and Fu1 Z.F., Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System. Journal of Virology. October 2005 vol. 79 no. 19 12554-12565<br />
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7 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
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[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
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Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91086Rabies2013-07-23T18:19:50Z<p>Daniel.E.Robinson-1: </p>
<hr />
<div>[[Image:OUA.png|thumb|200px|center|'''' Microbiology in Arezzo.]]<br />
[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically that phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Lethal Dose==<br />
Still haven't found a specific number, but don't worry Dr. Conway, I have emailed the CDC asking them what the number is.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the virus is extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammatory response can clearly be seen. The same inflammatory response can be seen when using an attenuated form of the wild type virus. [[#References|[6]]]<br />
<br />
=Diagnosis=<br />
[[Image:CDC1_post_mortem.gif|thumb|200px|right|''"Post mortem brain"'' Confirmed case of rabies by the CDC from post mortem testing. The brain weighed 1610g (normal 1300-1400). From: CDC.gov [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5913a3.htm]]]<br />
<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[7]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in contact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 Wang Z.W., Sarmento L, Wang Y, Li X-G, Dhingra V, Tseggai T, Jiang B, and Fu1 Z.F., Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System. Journal of Virology. October 2005 vol. 79 no. 19 12554-12565<br />
<br />
7 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91064Rabies2013-07-23T17:39:01Z<p>Daniel.E.Robinson-1: /* Host Immune Response */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically that phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Lethal Dose==<br />
Still haven't found a specific number, but don't worry Dr. Conway, I have emailed the CDC asking them what the number is.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the virus is extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammatory response can clearly be seen. The same inflammatory response can be seen when using an attenuated form of the wild type virus. [[#References|[6]]]<br />
<br />
=Diagnosis=<br />
[[Image:CDC1_post_mortem.gif|thumb|200px|right|''"Post mortem brain"'' Confirmed case of rabies by the CDC from post mortem testing. The brain weighed 1610g (normal 1300-1400). From: CDC.gov [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5913a3.htm]]]<br />
<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[7]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in contact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 Wang Z.W., Sarmento L, Wang Y, Li X-G, Dhingra V, Tseggai T, Jiang B, and Fu1 Z.F., Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System. Journal of Virology. October 2005 vol. 79 no. 19 12554-12565<br />
<br />
7 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91061Rabies2013-07-23T17:30:23Z<p>Daniel.E.Robinson-1: /* Lethal Dose */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically that phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Lethal Dose==<br />
Still haven't found a specific number, but don't worry Dr. Conway, I have emailed the CDC asking them what the number is.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammatory response can clearly be seen. The same inflammatory response can be seen when using an attenuated form of the wild type virus. [[#References|[6]]]<br />
<br />
=Diagnosis=<br />
[[Image:CDC1_post_mortem.gif|thumb|200px|right|''"Post mortem brain"'' Confirmed case of rabies by the CDC from post mortem testing. The brain weighed 1610g (normal 1300-1400). From: CDC.gov [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5913a3.htm]]]<br />
<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[7]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in contact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 Wang Z.W., Sarmento L, Wang Y, Li X-G, Dhingra V, Tseggai T, Jiang B, and Fu1 Z.F., Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System. Journal of Virology. October 2005 vol. 79 no. 19 12554-12565<br />
<br />
7 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=File:CDC1_post_mortem.gif&diff=91042File:CDC1 post mortem.gif2013-07-23T16:58:23Z<p>Daniel.E.Robinson-1: </p>
<hr />
<div></div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91041Rabies2013-07-23T16:57:59Z<p>Daniel.E.Robinson-1: /* Diagnosis */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically that phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Lethal Dose==<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammatory response can clearly be seen. The same inflammatory response can be seen when using an attenuated form of the wild type virus. [[#References|[6]]]<br />
<br />
=Diagnosis=<br />
[[Image:CDC1_post_mortem.gif|thumb|200px|right|''"Post mortem brain"'' Confirmed case of rabies by the CDC from post mortem testing. The brain weighed 1610g (normal 1300-1400). From: CDC.gov [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5913a3.htm]]]<br />
<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[7]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in contact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 Wang Z.W., Sarmento L, Wang Y, Li X-G, Dhingra V, Tseggai T, Jiang B, and Fu1 Z.F., Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System. Journal of Virology. October 2005 vol. 79 no. 19 12554-12565<br />
<br />
7 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91038Rabies2013-07-23T16:56:09Z<p>Daniel.E.Robinson-1: /* Diagnosis */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically that phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Lethal Dose==<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammatory response can clearly be seen. The same inflammatory response can be seen when using an attenuated form of the wild type virus. [[#References|[6]]]<br />
<br />
=Diagnosis=<br />
[[Image:CDC1_post_mortem|thumb|200px|right|''"Post mortem brain"'' Confirmed case of rabies by the CDC from post mortem testing. From: CDC.gov [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5913a3.htm]]]<br />
<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[7]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in contact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 Wang Z.W., Sarmento L, Wang Y, Li X-G, Dhingra V, Tseggai T, Jiang B, and Fu1 Z.F., Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System. Journal of Virology. October 2005 vol. 79 no. 19 12554-12565<br />
<br />
7 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91032Rabies2013-07-23T16:39:30Z<p>Daniel.E.Robinson-1: /* Pathogenisis */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically that phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Lethal Dose==<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammatory response can clearly be seen. The same inflammatory response can be seen when using an attenuated form of the wild type virus. [[#References|[6]]]<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[7]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in contact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 Wang Z.W., Sarmento L, Wang Y, Li X-G, Dhingra V, Tseggai T, Jiang B, and Fu1 Z.F., Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System. Journal of Virology. October 2005 vol. 79 no. 19 12554-12565<br />
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7 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
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[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
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Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91024Rabies2013-07-23T16:30:13Z<p>Daniel.E.Robinson-1: /* Host Immune Response */</p>
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<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically that phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammatory response can clearly be seen. The same inflammatory response can be seen when using an attenuated form of the wild type virus. [[#References|[6]]]<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[7]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in contact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 Wang Z.W., Sarmento L, Wang Y, Li X-G, Dhingra V, Tseggai T, Jiang B, and Fu1 Z.F., Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System. Journal of Virology. October 2005 vol. 79 no. 19 12554-12565<br />
<br />
7 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91021Rabies2013-07-23T16:29:26Z<p>Daniel.E.Robinson-1: /* Eliminating Rabies in Dogs */</p>
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<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically that phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammitory response can clearly be seen. The same inflammetory response can be seen when using an attenuated form of the wild type virus.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[7]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in contact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 Wang Z.W., Sarmento L, Wang Y, Li X-G, Dhingra V, Tseggai T, Jiang B, and Fu1 Z.F., Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System. Journal of Virology. October 2005 vol. 79 no. 19 12554-12565<br />
<br />
7 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91020Rabies2013-07-23T16:29:08Z<p>Daniel.E.Robinson-1: /* Eliminating Rabies in Dogs */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically that phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammitory response can clearly be seen. The same inflammetory response can be seen when using an attenuated form of the wild type virus.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[7]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 Wang Z.W., Sarmento L, Wang Y, Li X-G, Dhingra V, Tseggai T, Jiang B, and Fu1 Z.F., Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System. Journal of Virology. October 2005 vol. 79 no. 19 12554-12565<br />
<br />
7 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91019Rabies2013-07-23T16:28:47Z<p>Daniel.E.Robinson-1: /* References */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically that phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammitory response can clearly be seen. The same inflammetory response can be seen when using an attenuated form of the wild type virus.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 Wang Z.W., Sarmento L, Wang Y, Li X-G, Dhingra V, Tseggai T, Jiang B, and Fu1 Z.F., Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System. Journal of Virology. October 2005 vol. 79 no. 19 12554-12565<br />
<br />
7 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91009Rabies2013-07-23T16:23:03Z<p>Daniel.E.Robinson-1: /* Replication */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically that phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammitory response can clearly be seen. The same inflammetory response can be seen when using an attenuated form of the wild type virus.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91008Rabies2013-07-23T16:22:13Z<p>Daniel.E.Robinson-1: /* Disease */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Once the host reaches this stage of infection, the disease becomes absolutely lethal, effectively 100% of all hosts die from the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammitory response can clearly be seen. The same inflammetory response can be seen when using an attenuated form of the wild type virus.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91006Rabies2013-07-23T16:18:54Z<p>Daniel.E.Robinson-1: /* Incubation */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host. The more virus particles that enter the host and closer to the central nervous system, the shorter the incubation period.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammitory response can clearly be seen. The same inflammetory response can be seen when using an attenuated form of the wild type virus.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91004Rabies2013-07-23T16:17:41Z<p>Daniel.E.Robinson-1: /* Incubation */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years. The incubation is dependent on where the virus infects the host and the amount of virus particles inoculating the host.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammitory response can clearly be seen. The same inflammetory response can be seen when using an attenuated form of the wild type virus.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=91002Rabies2013-07-23T16:15:19Z<p>Daniel.E.Robinson-1: /* Host Immune Response */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Human testing is considered to be extremely unethical considering that the viruses extremely lethal. Testing has been conducted in animal models for immune responses and have come back with mixed results for various species of animals and the virus. An example if this is that mouse models have been used for testing with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus. When using the wild type (WTRV), little to no immune response was detected from the mice, however, when testing with the Silver-haired (SHBRV) a inflammitory response can clearly be seen. The same inflammetory response can be seen when using an attenuated form of the wild type virus.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=90993Rabies2013-07-23T15:22:13Z<p>Daniel.E.Robinson-1: /* Host Immune Response */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
Testing had been conducted in animal models for immune responses and have come back with mixed results for various subspecies of the virus. When testing mice with three forms of the virus including the wild type rabies (WTRV), silver-haired bat rabies virus (SHBRV), and attenuated virus.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=90971Rabies2013-07-23T13:02:05Z<p>Daniel.E.Robinson-1: /* Treatment */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Rabies is an extremely lethal disease with a almost absolute 100% death rate in all hosts in the late stages of the disease. there are only a hand full of documented human cases in which a person has the late stages of the disease and survives. The only way to treat the disease is before late stages of the virus can develop in the brain by using classical vaccination and antibodies treatments. Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
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[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
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Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=90961Rabies2013-07-23T12:49:48Z<p>Daniel.E.Robinson-1: </p>
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<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Host Immune Response=<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
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[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
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Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Campylobacteriosis&diff=90668Campylobacteriosis2013-07-22T21:18:37Z<p>Daniel.E.Robinson-1: /* Host Immune Response */</p>
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<div>{{Curated}}<br />
[[Image:OULOGOBIANCO.JPEG|thumb|230px|left|University of Oklahoma Study Abroad Microbiology in Arezzo, Italy[http://cas.ou.edu/study-abroad/]]]<br />
[[Image:Campylobacter.jpg|thumb|200px|right|''Spiral rod Campylobacter jejunum. From: Wikipedia.org [http://upload.wikimedia.org/wikipedia/commons/b/ba/Campylobacter.jpg]]]<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Proteobacteria]]<br />
| Class = [[Epsilon Proteobacteria]]<br />
| Order = [[Campylobacterales]]<br />
| Family = [[Campylobacteraceae]]<br />
| Genus = [[Campylobacter]]<br />
| Species = [[Salmonella jejuni]]<br />
<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=197&lvl=3&lin=f&keep=1&srchmode=1&unlock Taxonomy] Genome: <font size="2">[http://www.ncbi.nlm.nih.gov/genome/?term=Campylobacter+jejuni Genome]</font>'''<br />
|}<br />
===Description===<br />
Camplobacteriosis, caused by a bacterial infection of <i>Campylobacter jejuni</i> in the human body, is the most common cause of diarrhea in the United States. <i>Campylobacter</i> is a Gram-negative spiral bacterium which damages the small intestine and colon. This pathogenic bacterium causes bloody diarrhea, vomiting, abdominal pain, and fever. [[#References|[1]]] <i>Campylobacter</i> is microaerophilic as well as a thermophile and takes 2-5 days to begin showing symptoms. Diarrhea and related symptoms are self-limiting, and typically last 5-7 days. This non-spore forming prokaryote was isolated in 1972 and genome sequenced in 2000. [[#References|[2]]] <i>Campylobacter</i> usually occurs in isolated events affecting 1.3 million people a year. <i>C. jejuni</i> has a very low infectious dose with only 500 organisms being required for symptoms to present in an infected host. <i>C. jejuni</i> are motile pathogens that causes disease by producing cytolethal distending toxin, which stops the cell from dividing and activating the immune system. This helps <i>C. jejuni</i> to evade the small intestine and colon. <i>Campylobacter</i> is transmitted by raw or uncooked poultry, unpasteurized dairy, contaminated water, produce, and stool from animals or humans. It is rarely passed from human to human, but rather through consumption of infected food. Prevention is possible by simply cooking meat thoroughly; washing hands, and not using contaminated cooking utensils for uncooked goods. While some antibiotics such as Azithromycin are used to treat the illness, most people abstain from medicine allowing the pathogen to run its course while replenishing the body with water and electrolytes. In rare incidents <i>Camplobacter</i> can cause long term consequences such as arthritis, Guillian-Barre syndrome, and gastrointestinal perforation. <i>C. jejuni</i> is estimated to kill 76 people a year, mostly infants and children. To diagnose <i>Camplobacter</i> as the infectious agent of the disease, fecal matter must be cultured.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
<i>Campylobacter</i> is transmitted by ingesting contaminated food and water as well as human to human contact. Roughly 57% of cases can be traced to chickens and 35% to cattle. Animal farms, as well as slaughterhouses, were found to have a high infestation of <i>Campylobacter</i>[[#References|[3]]]. Transmission can be found in cross-contamination of animal farms and water supply such as contamination in ones own kitchen. Unpasteurized milk also transmits <i>Campylobacter</i> through utter infection and contact with milk. <i>Campylobacter</i> is most common in developing countries, thus 19% of diagnosed <i>C. jejuni</i> infections are associated with international travel.<br />
<br />
===Infectious Dose, Incubation, Colonization=== <br />
The infectious dose of C. <i>jejuni</i> is around 500 organisms [[#References|[4]]]. This is relatively low compared to some of the other gastrointestinal pathogens. The incubation period for this organism is one-eleven days with the average being two-five days. C. <i>jejuni</i> typically colonizes the small intestine and colon through the use of virulence factors such as motility, chemotaxis, adhesion, and invasion. Flagellin are very important in this process. Colonization typically occurs in children under 5 or in young adults.<br />
<br />
===Epidemiology=== <br />
<i>Campylobacter jejuni</i> is prevalent in the United States and other developed countries. The first isolation of Campylobacteriosis was in 1972 [[#References|[5]]]<br />
. The majority of campylobacteriosis cases are sporadic with only 3% being associated with households and 2.3% being in a cluster[[#References|[6]]]. Campylobacteriosis is often underreported so numbers of infected persons per year are often low. It is estimated that around 70% of poultry are infected with <i>Campylobacter</i> depending on the region [[#References|[7]]]. The incidence of disease has remained stable in the past few years [[#References|[8]]].<br />
<br />
===Virulence Factors=== <br />
<i>C. jejuni</i> has many virulence factors that attribute to its pathogenicity in humans. Flagellin contribute to the bacteria's motility which allows it to travel throughout the host [[#References|[9]]]. Another portion of the flagella's virulence is chemotaxis, which includes sensing the environment and rotating the flagella accordingly to benefit the bacteria. Mucin has been found to be a positive chemotaxin for C. <i>jejuni</i> which is compatible with the bacteria’s colonization of the intestine where there is abundant mucus. This virulence factor would serve as a guide towards colonization for the bacteria. Bile and L-fucose are also positive chemotaxins for C. <i>jejuni</i>. Motility and chemotaxis help lead the bacteria to its colonization site. It has been found that motility is a necessary component for the bacteria to be virulent[[#References|[10]]].<br />
<br /><br />Adhesion and invasion are important virulence factors for colonizing the host's intestinal cells. Adhesion is a necessary part of virulence for this bacteria because it allows <i>C. jejuni</i> to stay on the host cell long enough to cross into it. Adhesion is possible through various proteins, flagella, and lipopolysaccharide. Once adhered, the bacteria can be taken up by a cytoplasmic vacuole. The bacteria invade the host cell barriers through the use of flagellin. <br />
<br /><br /> <i>C. jejuni</i> also contains virulence factors based on its cell wall. Gram-negative bacteria contain lipopolysaccharides (LPS) in their outer membrane. This LPS plays a role in adherence as well as evading the immune system. The bacteria have the ability to shift its LPS antigen composition which makes it harder for the immune system to detect the pathogen. An important factor in contracting Guillians Barre syndrome from this pathogen is the sialic acid that is contained in its core oligosaccharide. This compound can resemble gangliosides which can cause this neurological disease. <br /><br />The bacteria’s core toxicity pathway is cytolethal distending toxin. This toxin stops the cell’s growth cycle in G2 and the cell eventually dies. The cell death that accompanies this toxin is a reason for blood in the host’s diarrhea. This toxin is also thought to cause immunosuppression. There are three portions of this toxin, CdtA, CdtB, and CdtC. Little is known about the exact mechanism the three portions have for carrying out the disease. But CdtB is a known nuclease, which can disrupt DNA in the cell. <br />
<br /><br />Iron acquisition is important for sustaining nutrients within the host. <i>C. jejuni</i> accomplishes this through using heme compounds, siderophores, and ferric iron. Iron is important for electron transport, anaerobic respiration, and energy metabolism. Superoxide dismutase is also one of the virulence factors for <i>C. jejuni</i> because it gets rid of the reactive oxygen species superoxide which could harm the cell's DNA or membrane factors. Antibiotic resistance to tetracycline, erythromycin, ciprofloxacin, kanamycin, nalidixic acid, and chloramphenicol is important for staying within the host to carry out its pathogenesis.<br />
<br />
==Clinical features==<br />
===Symptoms=== <br />
<i>Campylobacteriosis</i> can often go undiagnosed or it is often underreported because it is one of many diarrheal diseases. The disease is characterized by bloody or mucosal diarrhea[[#References|[4]]]. The diarrhea is a result of the bacteria's colonization in the intestine and cell death due to the cytolethal toxin. Other symptoms may include muscle pain, headache, fever, and nausea which are due to dehydration from the diarrhea. The disease is self-limiting and most symptoms cease after five days. Reactive arthritis, Guillain-Barré syndrome, and bacteremia are known side effects of this disease, but they rarely occur. Guillain-Barré syndrome could occur several weeks after the diarrhea symptoms. This is due to the bacteria's role in mimicking the gangliosides of the neural system which can lead to the immune system attacking self cells. This may lead to paralysis, but is usually recoverable. Bacteremia may be a result but mostly effects the immunocompromised or elderly. This can lead to death in the host.<br />
<br />
===Morbidity and Mortality===<br />
<i>Campylobacter</i> has a high infection rate of 1.3 million a year and a low mortality rate of 76 a year. Mortality is usually due to rare complications such as Guillain-Barre syndrome and impoverished environments dehydration. For the most part <i>Campylobacter</i> passes through ones system without any residual effects.<br />
<br />
==Diagnosis==<br />
Diagnosis of <i>Campylobacter</i> is done by confirming its presence in the patient’s stool. The two methods currently used in identification are growth on a selective medium such as Preston <i>Campylobacter</i> selective agar [[#References|[10]]] and Polymerization Chain Reaction (PCR) [[#References|[11]]] to determine the DNA presence of <i>Campylobacter jejuni</i> as well as other related species and subspecies.<br />
<br />
==Treatment==<br />
Treatment of Campylobacteriosis is done by managing the symptoms and any complications until the symptoms subside. Symptoms mainly include diarrhea leading to dehydration, and vomiting. Antibiotics can be used but are not usually administered unless serious complications arise. A majority of people recover from the symptoms within a week; however, some cases have known to take up to approximately 10 days.<br />
<br />
Replacement of fluids and electrolytes lost during diarrhea and vomiting are keys to recovery and preventing symptoms from being prolonged. Water or rehydration drinks are recommended. Drinks such as soda and fruit juices contain too much sugar and too few electrolytes to be considered effective treatments for dehydration.<br />
<br />
Maintaining a normal diet as much as possible will help in recovering faster. Avoid foods that have high fat and sugar content as well as spicy foods, alcohol, and coffee until approximately 2 days after symptoms subside.<br />
<br />
==Prevention==<br />
Several leading organizations including WHO, CDC, FDA, USDA, and state health departments have ongoing studies, investigations, and monitoring of <i>Campylobacter</i> across the world. Although the bacteria spreads through fecal oral transmission, a majority of infections occur from food born contamination, especially unpasteurized milk and poultry products.<br />
===Risk Avoidance===<br />
Proper food handling and hand washing skills are key practices to prevent the spread of <i>Campylobacter jejuni</i>. <br />
<br />
• Make sure that the meat is cooked throughout (no longer pink in the center). All poultry should be cooked to at least an internal temperature of 165°F.<br />
<br />
• Wash hands with soap before and after preparing food, especially raw meats.<br />
<br />
• Prevent cross-contamination while preparing foods by using separate cutting boards for raw meats and other foods<br />
<br />
• Cleaning all cutting boards, kitchen countertops, and silverware with soap and hot water.<br />
<br />
• Do not drink unpasteurized milk or untreated surface water.<br />
<br />
• Be sure that persons with diarrhea wash their hands carefully and frequently with soap to help reduce the risk of spreading the infection.<br />
<br />
• Washing hands with soap after coming in contact with pet feces.<br />
<br />
===Immunization===<br />
Studies are still ongoing as to human vaccinations and immunizations against <i>Campylobacter jejuni</i>. Currently there are Immunizations available to chickens. Conventional methods of using heat or chemically killed vaccines have not completely protected against infection occurring. Using nanoparticales and constructing a DNA vaccine that targets the flagellum of the bacteria, which is a key mechanism of attachment in the gastrointestinal tract, have resulted in a significant decrease in the campylobacter’s ability to colonize the host.[[#References|[12]]]<br />
<br />
==Host Immune Response==<br />
The innate immune response from the host includes several things such as TLR's (toll like receptors), serum type, and sugars. <i>Campylobacter</i> has evolved to specifically overcome a few of the immune system's most basic responses including the TLR5 receptors that recognize the flagellum of the bacterium, and also the TLR9 receptors responsible for recognition of CpG di-nucleotides present in <i>Campylobacter</i>. Other experiments have also shown the importance of downstream TLR's in the immune response and their stimulation against the disease. Macrophage activation from NOD1 receptors and their mediation play a part in <i>Campylobacter's</i> plan to circumvent the innate immune response. Studies have also been conducted as to the role of fucosylated sugars in breast milk and how their presence prevents the attachment of <i>Campylobacter</i> to the intestinal mucosa. <i>C. jejuni</i> is found to be sensitive to specific types of serum, emphizising the importance of compliment mediated responses of the immune response. <br />
<br />
The adaptive Immune response has developed several responses to many antigens present on the bacterium. Some tests using human volunteers have shown the earliest signs of antibody presence as approximately 6-7 days after inoculation. Of the antibodies that are detected there are several of isotypes. Almost unsurprisingly, many of the antigens recognized by antibodies come from <i>Campylobacter's</i> more prodominant virulence fators including the bacterial flagellum, many periplasmic proteins, capsular polysaccharides, and the CDT toxin.<br />
<br />
==References==<br />
1 Centers for Disease Control and Prevention (2010), Campylobacter <http://www.cdc.gov/nczved/divisions/dfbmd/diseases/campylobacter.><br />
<br />
2 “Campylobacter.” Wikipedia: The Free Encyclopedia. Wikimedia Foundation, Inc., (15 July 2013). Web. (14 July 2013). <http://en.wikipedia.org/wiki/Campylobacter><br />
<br />
3 Nordqvist, Christian. "Transmission Routes For The Bacterium Campylobacter." Medical News Today. MediLexicon, Intl., 28 Dec. 2006. Web.<br />
16 Jul. 2013. <http://www.medicalnewstoday.com/releases/59254.php><br />
<br />
4 Curtis, Laurie. "Campylobacter." Food Safety Watch. Nov. 2007. Web. 13 July 2013. <http://www.foodsafetywatch.com/public/498.cfm>.<br />
<br />
5 Vauxe, Robert. Centers for Disease Control and Prevention. 1 June 1988. Web. 16 July 2013. <http://www.cdc.gov/mmwr/preview/mmwrhtml/00001764.htm>.<br />
<br />
6"Factors Associated with Geographic and Temporal Variation in Campylobacteriosis in Humans." Food Standards Agency. 5 Oct. 2011. Web. 13 July 2013. <http://food.gov.uk/science/research/devolvedadmins/scotlandresearch/scotlandresearch/ScotlandProjectList/s14004/#.UeLVY-At9bo>.<br />
<br />
7 "Causes of Foodborne Illness: Bad Bug Book." Food and Drug Administration. 15 Mar. 2013. Web. 16 July 2013. <http://www.fda.gov/Food/FoodborneIllnessContaminants/CausesOfIllnessBadBugBook/ucm070024.htm>.<br />
<br />
8 "Preliminary FoodNet Data on the Incidence of Infection with Pathogens Transmitted Commonly Through Food." Centers for Disease Control and Prevention. 10 Apr. 2009. Web. 16 July 2013. <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5813a2.htm>.<br />
<br />
9 S.P. Bhavsar, B.P. Kapadnis: Virulence factors of Campylobacter. The Internet Journal of Microbiology. 2007 Volume 3 Number 2. DOI: 10.5580/62b - See more at: http://archive.ispub.com/journal/the-internet-journal-of-microbiology/volume-3-number-2/virulence-factors-of-campylobacter.html#sthash.8GNLneuR.bzVE2MRq.dpuf<br />
<br />
10 Grant, Christopher C. R., Michael. E. Konkel, Wietold Cieplak, Lucy Tompkins, "Role of Flagella in Adherence, Internalization, and Translocation of Campylobacter jejuni in Nonpolarized and Polarized Epithelial Cell Cultures" American Society for Microbiology. May 1993. <http://iai.asm.org/content/61/5/1764.long>.<br />
<br />
11 Bolton F.J. and Robertson L., 1982, Journal of Clinical Pathology 35, pg. 462-467<br />
<br />
12 Mao-Jun Zhang, Bo Qiao, Xue-Bin Xu, and Jian-Zhong Zhang, World J Gastroenterol. May 28,2013,<br />
19(20): 3090–3095. Published online 2013 May 28. doi: 10.3748/wjg.v19.i20.3090, PMC3662949 <http://www.wjgnet.com/1007-9327/journal/v19/i20/><br />
<br />
13 Jin-lin Huang, Yan-Xin Yin, [...], and Xin-an Jiao, Intranasal Immunization with Chitosan/pCAGGS-flaA Nanoparticles Inhibits Campylobacter jejuni in a White Leghorn Model, Journal of Biomedicine and Biotechnology. 2010; 2010: 589476<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948919/><br />
<br />
Created by Halen Borron, Kelley Raines, and Evan Robinson, students of Tyrrell Conway at the University of Oklahoma.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Campylobacteriosis&diff=90555Campylobacteriosis2013-07-22T19:00:17Z<p>Daniel.E.Robinson-1: /* Host Immune Response */</p>
<hr />
<div>{{Curated}}<br />
[[Image:OULOGOBIANCO.JPEG|thumb|230px|left|University of Oklahoma Study Abroad Microbiology in Arezzo, Italy[http://cas.ou.edu/study-abroad/]]]<br />
[[Image:Campylobacter.jpg|thumb|200px|right|''Spiral rod Campylobacter jejunum. From: Wikipedia.org [http://upload.wikimedia.org/wikipedia/commons/b/ba/Campylobacter.jpg]]]<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Proteobacteria]]<br />
| Class = [[Epsilon Proteobacteria]]<br />
| Order = [[Campylobacterales]]<br />
| Family = [[Campylobacteraceae]]<br />
| Genus = [[Campylobacter]]<br />
| Species = [[Salmonella jejuni]]<br />
<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=197&lvl=3&lin=f&keep=1&srchmode=1&unlock Taxonomy] Genome: <font size="2">[http://www.ncbi.nlm.nih.gov/genome/?term=Campylobacter+jejuni Genome]</font>'''<br />
|}<br />
===Description===<br />
Camplobacteriosis, caused by a bacterial infection of <i>Campylobacter jejuni</i> in the human body, is the most common cause of diarrhea in the United States. <i>Campylobacter</i> is a Gram-negative spiral bacterium which damages the small intestine and colon. This pathogenic bacterium causes bloody diarrhea, vomiting, abdominal pain, and fever. [[#References|[1]]] <i>Campylobacter</i> is microaerophilic as well as a thermophile and takes 2-5 days to begin showing symptoms. Diarrhea and related symptoms are self-limiting, and typically last 5-7 days. This non-spore forming prokaryote was isolated in 1972 and genome sequenced in 2000. [[#References|[2]]] <i>Campylobacter</i> usually occurs in isolated events affecting 1.3 million people a year. <i>C. jejuni</i> has a very low infectious dose with only 500 organisms being required for symptoms to present in an infected host. <i>C. jejuni</i> are motile pathogens that causes disease by producing cytolethal distending toxin, which stops the cell from dividing and activating the immune system. This helps <i>C. jejuni</i> to evade the small intestine and colon. <i>Campylobacter</i> is transmitted by raw or uncooked poultry, unpasteurized dairy, contaminated water, produce, and stool from animals or humans. It is rarely passed from human to human, but rather through consumption of infected food. Prevention is possible by simply cooking meat thoroughly; washing hands, and not using contaminated cooking utensils for uncooked goods. While some antibiotics such as Azithromycin are used to treat the illness, most people abstain from medicine allowing the pathogen to run its course while replenishing the body with water and electrolytes. In rare incidents <i>Camplobacter</i> can cause long term consequences such as arthritis, Guillian-Barre syndrome, and gastrointestinal perforation. <i>C. jejuni</i> is estimated to kill 76 people a year, mostly infants and children. To diagnose <i>Camplobacter</i> as the infectious agent of the disease, fecal matter must be cultured.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
<i>Campylobacter</i> is transmitted by ingesting contaminated food and water as well as human to human contact. Roughly 57% of cases can be traced to chickens and 35% to cattle. Animal farms, as well as slaughterhouses, were found to have a high infestation of <i>Campylobacter</i>[[#References|[3]]]. Transmission can be found in cross-contamination of animal farms and water supply such as contamination in ones own kitchen. Unpasteurized milk also transmits <i>Campylobacter</i> through utter infection and contact with milk. <i>Campylobacter</i> is most common in developing countries, thus 19% of diagnosed <i>C. jejuni</i> infections are associated with international travel.<br />
<br />
===Infectious Dose, Incubation, Colonization=== <br />
The infectious dose of C. <i>jejuni</i> is around 500 organisms [[#References|[4]]]. This is relatively low compared to some of the other gastrointestinal pathogens. The incubation period for this organism is one-eleven days with the average being two-five days. C. <i>jejuni</i> typically colonizes the small intestine and colon through the use of virulence factors such as motility, chemotaxis, adhesion, and invasion. Flagellin are very important in this process. Colonization typically occurs in children under 5 or in young adults.<br />
<br />
===Epidemiology=== <br />
<i>Campylobacter jejuni</i> is prevalent in the United States and other developed countries. The first isolation of Campylobacteriosis was in 1972 [[#References|[5]]]<br />
. The majority of campylobacteriosis cases are sporadic with only 3% being associated with households and 2.3% being in a cluster[[#References|[6]]]. Campylobacteriosis is often underreported so numbers of infected persons per year are often low. It is estimated that around 70% of poultry are infected with <i>Campylobacter</i> depending on the region [[#References|[7]]]. The incidence of disease has remained stable in the past few years [[#References|[8]]].<br />
<br />
===Virulence Factors=== <br />
<i>C. jejuni</i> has many virulence factors that attribute to its pathogenicity in humans. Flagellin contribute to the bacteria's motility which allows it to travel throughout the host [[#References|[9]]]. Another portion of the flagella's virulence is chemotaxis, which includes sensing the environment and rotating the flagella accordingly to benefit the bacteria. Mucin has been found to be a positive chemotaxin for C. <i>jejuni</i> which is compatible with the bacteria’s colonization of the intestine where there is abundant mucus. This virulence factor would serve as a guide towards colonization for the bacteria. Bile and L-fucose are also positive chemotaxins for C. <i>jejuni</i>. Motility and chemotaxis help lead the bacteria to its colonization site. It has been found that motility is a necessary component for the bacteria to be virulent[[#References|[10]]].<br />
<br /><br />Adhesion and invasion are important virulence factors for colonizing the host's intestinal cells. Adhesion is a necessary part of virulence for this bacteria because it allows <i>C. jejuni</i> to stay on the host cell long enough to cross into it. Adhesion is possible through various proteins, flagella, and lipopolysaccharide. Once adhered, the bacteria can be taken up by a cytoplasmic vacuole. The bacteria invade the host cell barriers through the use of flagellin. <br />
<br /><br /> <i>C. jejuni</i> also contains virulence factors based on its cell wall. Gram-negative bacteria contain lipopolysaccharides (LPS) in their outer membrane. This LPS plays a role in adherence as well as evading the immune system. The bacteria have the ability to shift its LPS antigen composition which makes it harder for the immune system to detect the pathogen. An important factor in contracting Guillians Barre syndrome from this pathogen is the sialic acid that is contained in its core oligosaccharide. This compound can resemble gangliosides which can cause this neurological disease. <br /><br />The bacteria’s core toxicity pathway is cytolethal distending toxin. This toxin stops the cell’s growth cycle in G2 and the cell eventually dies. The cell death that accompanies this toxin is a reason for blood in the host’s diarrhea. This toxin is also thought to cause immunosuppression. There are three portions of this toxin, CdtA, CdtB, and CdtC. Little is known about the exact mechanism the three portions have for carrying out the disease. But CdtB is a known nuclease, which can disrupt DNA in the cell. <br />
<br /><br />Iron acquisition is important for sustaining nutrients within the host. <i>C. jejuni</i> accomplishes this through using heme compounds, siderophores, and ferric iron. Iron is important for electron transport, anaerobic respiration, and energy metabolism. Superoxide dismutase is also one of the virulence factors for <i>C. jejuni</i> because it gets rid of the reactive oxygen species superoxide which could harm the cell's DNA or membrane factors. Antibiotic resistance to tetracycline, erythromycin, ciprofloxacin, kanamycin, nalidixic acid, and chloramphenicol is important for staying within the host to carry out its pathogenesis.<br />
<br />
==Clinical features==<br />
===Symptoms=== <br />
<i>Campylobacteriosis</i> can often go undiagnosed or it is often underreported because it is one of many diarrheal diseases. The disease is characterized by bloody or mucosal diarrhea[[#References|[4]]]. The diarrhea is a result of the bacteria's colonization in the intestine and cell death due to the cytolethal toxin. Other symptoms may include muscle pain, headache, fever, and nausea which are due to dehydration from the diarrhea. The disease is self-limiting and most symptoms cease after five days. Reactive arthritis, Guillain-Barré syndrome, and bacteremia are known side effects of this disease, but they rarely occur. Guillain-Barré syndrome could occur several weeks after the diarrhea symptoms. This is due to the bacteria's role in mimicking the gangliosides of the neural system which can lead to the immune system attacking self cells. This may lead to paralysis, but is usually recoverable. Bacteremia may be a result but mostly effects the immunocompromised or elderly. This can lead to death in the host.<br />
<br />
===Morbidity and Mortality===<br />
<i>Campylobacter</i> has a high infection rate of 1.3 million a year and a low mortality rate of 76 a year. Mortality is usually due to rare complications such as Guillain-Barre syndrome and impoverished environments dehydration. For the most part <i>Campylobacter</i> passes through ones system without any residual effects.<br />
<br />
==Diagnosis==<br />
Diagnosis of <i>Campylobacter</i> is done by confirming its presence in the patient’s stool. The two methods currently used in identification are growth on a selective medium such as Preston <i>Campylobacter</i> selective agar [[#References|[10]]] and Polymerization Chain Reaction (PCR) [[#References|[11]]] to determine the DNA presence of <i>Campylobacter jejuni</i> as well as other related species and subspecies.<br />
<br />
==Treatment==<br />
Treatment of Campylobacteriosis is done by managing the symptoms and any complications until the symptoms subside. Symptoms mainly include diarrhea leading to dehydration, and vomiting. Antibiotics can be used but are not usually administered unless serious complications arise. A majority of people recover from the symptoms within a week; however, some cases have known to take up to approximately 10 days.<br />
<br />
Replacement of fluids and electrolytes lost during diarrhea and vomiting are keys to recovery and preventing symptoms from being prolonged. Water or rehydration drinks are recommended. Drinks such as soda and fruit juices contain too much sugar and too few electrolytes to be considered effective treatments for dehydration.<br />
<br />
Maintaining a normal diet as much as possible will help in recovering faster. Avoid foods that have high fat and sugar content as well as spicy foods, alcohol, and coffee until approximately 2 days after symptoms subside.<br />
<br />
==Prevention==<br />
Several leading organizations including WHO, CDC, FDA, USDA, and state health departments have ongoing studies, investigations, and monitoring of <i>Campylobacter</i> across the world. Although the bacteria spreads through fecal oral transmission, a majority of infections occur from food born contamination, especially unpasteurized milk and poultry products.<br />
===Risk Avoidance===<br />
Proper food handling and hand washing skills are key practices to prevent the spread of <i>Campylobacter jejuni</i>. <br />
<br />
• Make sure that the meat is cooked throughout (no longer pink in the center). All poultry should be cooked to at least an internal temperature of 165°F.<br />
<br />
• Wash hands with soap before and after preparing food, especially raw meats.<br />
<br />
• Prevent cross-contamination while preparing foods by using separate cutting boards for raw meats and other foods<br />
<br />
• Cleaning all cutting boards, kitchen countertops, and silverware with soap and hot water.<br />
<br />
• Do not drink unpasteurized milk or untreated surface water.<br />
<br />
• Be sure that persons with diarrhea wash their hands carefully and frequently with soap to help reduce the risk of spreading the infection.<br />
<br />
• Washing hands with soap after coming in contact with pet feces.<br />
<br />
===Immunization===<br />
Studies are still ongoing as to human vaccinations and immunizations against <i>Campylobacter jejuni</i>. Currently there are Immunizations available to chickens. Conventional methods of using heat or chemically killed vaccines have not completely protected against infection occurring. Using nanoparticales and constructing a DNA vaccine that targets the flagellum of the bacteria, which is a key mechanism of attachment in the gastrointestinal tract, have resulted in a significant decrease in the campylobacter’s ability to colonize the host.[[#References|[12]]]<br />
<br />
==Host Immune Response==<br />
The Innate immune response from the host includes several things such as TLR's (toll like recepttors), Serum type, and sugars having an important role. Campylobacter has evolved to specifically overcome a few of the immune systems most basic responses including the TLR5 receptors that recognize the flagellum of the bacterium, and also the TLR9 receptors responsible for recognition of CpG di-nucleotides present in Campylobacter. Other experiments have also shown the importance many downstream TLR's in the immune response and their stimulation against the disease. Macrophage activation from NOD1 receptors and their mediation play a part in campylobacter's plan to circumvent the innate immune response. Studies have also been conducted as to the role of fucosylated sugars in breast milk and how their presence prevents the attachment of Campylobacter to the intestinal mucosa. C. jejuni is found to be sensitive to specific types of serum, emphizising the importance of compliment mediated responses of the immune response. <br />
<br />
The adaptive Immune response has developed several responses to many antigens present on the bacterium. Some tests using human volunteers has shown that the earliest signs of antibody presence as approximately 6-7 days after inoculation. Of the antibodies that are detected are several of isotypes. Almost unsurprisingly, many of the antigens recognized by antibodies come from campylobacters more prodominant virulence fators including the bacterial flagellum, many periplasmic proteins, capsular polysaccharides, and the CDT toxin.<br />
<br />
==References==<br />
1 Centers for Disease Control and Prevention (2010), Campylobacter <http://www.cdc.gov/nczved/divisions/dfbmd/diseases/campylobacter.><br />
<br />
2 “Campylobacter.” Wikipedia: The Free Encyclopedia. Wikimedia Foundation, Inc., (15 July 2013). Web. (14 July 2013). <http://en.wikipedia.org/wiki/Campylobacter><br />
<br />
3 Nordqvist, Christian. "Transmission Routes For The Bacterium Campylobacter." Medical News Today. MediLexicon, Intl., 28 Dec. 2006. Web.<br />
16 Jul. 2013. <http://www.medicalnewstoday.com/releases/59254.php><br />
<br />
4 Curtis, Laurie. "Campylobacter." Food Safety Watch. Nov. 2007. Web. 13 July 2013. <http://www.foodsafetywatch.com/public/498.cfm>.<br />
<br />
5 Vauxe, Robert. Centers for Disease Control and Prevention. 1 June 1988. Web. 16 July 2013. <http://www.cdc.gov/mmwr/preview/mmwrhtml/00001764.htm>.<br />
<br />
6"Factors Associated with Geographic and Temporal Variation in Campylobacteriosis in Humans." Food Standards Agency. 5 Oct. 2011. Web. 13 July 2013. <http://food.gov.uk/science/research/devolvedadmins/scotlandresearch/scotlandresearch/ScotlandProjectList/s14004/#.UeLVY-At9bo>.<br />
<br />
7 "Causes of Foodborne Illness: Bad Bug Book." Food and Drug Administration. 15 Mar. 2013. Web. 16 July 2013. <http://www.fda.gov/Food/FoodborneIllnessContaminants/CausesOfIllnessBadBugBook/ucm070024.htm>.<br />
<br />
8 "Preliminary FoodNet Data on the Incidence of Infection with Pathogens Transmitted Commonly Through Food." Centers for Disease Control and Prevention. 10 Apr. 2009. Web. 16 July 2013. <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5813a2.htm>.<br />
<br />
9 S.P. Bhavsar, B.P. Kapadnis: Virulence factors of Campylobacter. The Internet Journal of Microbiology. 2007 Volume 3 Number 2. DOI: 10.5580/62b - See more at: http://archive.ispub.com/journal/the-internet-journal-of-microbiology/volume-3-number-2/virulence-factors-of-campylobacter.html#sthash.8GNLneuR.bzVE2MRq.dpuf<br />
<br />
10 Grant, Christopher C. R., Michael. E. Konkel, Wietold Cieplak, Lucy Tompkins, "Role of Flagella in Adherence, Internalization, and Translocation of Campylobacter jejuni in Nonpolarized and Polarized Epithelial Cell Cultures" American Society for Microbiology. May 1993. <http://iai.asm.org/content/61/5/1764.long>.<br />
<br />
11 Bolton F.J. and Robertson L., 1982, Journal of Clinical Pathology 35, pg. 462-467<br />
<br />
12 Mao-Jun Zhang, Bo Qiao, Xue-Bin Xu, and Jian-Zhong Zhang, World J Gastroenterol. May 28,2013,<br />
19(20): 3090–3095. Published online 2013 May 28. doi: 10.3748/wjg.v19.i20.3090, PMC3662949 <http://www.wjgnet.com/1007-9327/journal/v19/i20/><br />
<br />
13 Jin-lin Huang, Yan-Xin Yin, [...], and Xin-an Jiao, Intranasal Immunization with Chitosan/pCAGGS-flaA Nanoparticles Inhibits Campylobacter jejuni in a White Leghorn Model, Journal of Biomedicine and Biotechnology. 2010; 2010: 589476<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948919/><br />
<br />
Created by Halen Borron, Kelley Raines, and Evan Robinson, students of Tyrrell Conway at the University of Oklahoma.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=90313Rabies2013-07-22T12:51:53Z<p>Daniel.E.Robinson-1: /* Symptoms */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains associated with drinking water. Other possible symptoms include hallucinations and seizures from neuron degradation in the central nervous system. The virus can lead to many various symptoms not all are required for a clinical diagnosis, but all eventually lead to respiratory failure. Some cases have been documented only showing symptoms of paralysis leading to coma and eventually respiratory failure. The symptoms of rabies can be vivid and graphic in their appearance, but none can completely confirm the diseases presence in a host.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=90277Rabies2013-07-22T12:32:22Z<p>Daniel.E.Robinson-1: /* Pathogenisis */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Symptoms==<br />
During the incubation/Prodormal periods of the disease, symptoms may include itching and burning sensation at the wound or bite, fever, headache, and gastrointestinal problems. As the disease progresses into the neurological phase, about half of all cases begin to show hydrophobia and pains in drinking water.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
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6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
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[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
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Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Clostridium_difficile-associated_disease&diff=90059Clostridium difficile-associated disease2013-07-22T09:25:30Z<p>Daniel.E.Robinson-1: /* Moderate to severe cases */</p>
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<div>{{Curated}}<br />
[[File:Clostridium difficile spore.gif|400px|thumb|right|Scanning electron microscope image of <i>Clostridium difficile</i>. From: Bioquell.com [http://www.bioquell.com/technology/microbiology/clostridium-difficile/]]]<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Firmicutes]]<br />
| Class = [[Clostridia]]<br />
| Order = [[Clostridiales]]<br />
| Family = [[Clostridiaceae]]<br />
| Genus = [[Clostridium]]<br />
| species = [[C. difficile]]<br />
<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=1496&lvl=3&lin=f&keep=1&srchmode=1&unlock Taxonomy] Genome: <font size="2">[http://www.ncbi.nlm.nih.gov/genome/?term=clostridium+difficile Genome]</font>'''<br />
|}<br />
<br />
===Description===<br />
<i>Clostridium difficile</i> causes pseudomembranous colitis, toxic megacolon, perforations of the colon, sepsis, and, on occasion, death. It is a Gram-positive, spore-forming rod that is an obligate anaerobe. It can be found in soil, water, feces, and the human gut. <i>C. difficile</i> is a normal inhabitant of the gut microbial community of about 1-3% of adults. The pathogenic form of <i>C. difficile</i> is transferred via the fecal-oral route as well as through spore dispersal. <i>Clostridium difficile</i>-associated disease (CDAD) was initially reported approximately 30 years ago. The CDC first recorded infections from a hyper-virulent strain in 2000 along with a marked increase in the number of CDAD infections. <i>C. difficile</i> causes disease by producing the toxins TcdA and TcdB that function to disrupt protein synthesis within the host cell. The toxins are responsible for producing symptoms such as watery diarrhea, fever, loss of appetite, nausea, and severe abdominal pain (1). Although <i>C. difficile</i> only causes about 20% of antibiotic associated colitis, standard treatments fail in about 25% of CDAD cases. Patients treated promptly typically recover. However, CDAD is notorious for recurrence after initial antibiotic treatment. 33% of patients with an infection will have a recurrence with 64% of those being within 30 days of the initial infection (2). Complications typically develop in about 11% of patients in the first recurrence. This likely promotes the growth of antibiotic resistant strains that are able to perform horizontal gene transfer between recurrences. In about 20% of patients the infection will resolve itself in 2-3 of discontinuing the inciting antibiotic. Most infections that persist are treated with a 10-14 day course of antibiotics like metronidazole, vancomycin, and rehydration therapy. In more serious cases fecal transplants and surgery can be performed [[#References|[3]]]. Patients at risk for developing CDAD include those taking antibiotics (especially broad spectrum), those taking proton pump inhibitors, GI manipulation or surgery, long term stays in hospital or clinical settings, immunocompromising conditions, and old age. The best practices for preventing infection include judicious administration of antibiotics, quarantine, hand hygiene, and the use of EPA-registered disinfectants with a sporicide (especially hypochlorite based disinfectants).<br />
<br />
==Pathogenesis==<br />
[[File:Clostridium difficile pathogenesis.jpeg|500px|thumb|right|Pathogenesis of <i>Clostridium difficile</i> and formation of pseudomembranes. From: Nature.com [http://www.nature.com/nrmicro/journal/v7/n7/fig_tab/nrmicro2164_F5.html]]]<br />
<br />
===Transmission===<br />
<i>Clostridium difficile</i> are shed in feces, and therefore this bacteria can be transmitted via the fecal-oral route. The spores can survive on almost any surface for months to years, making the pathogen very difficult to get rid of once established. The spores are resistant to many extreme environments, including high temperatures, ultraviolet light, harsh chemicals, and antibiotics. Health care settings, including patients and workers, are often the reservoirs for <i>C. difficile</i> spores. Community-acquired infections are thought to be transmitted through soil, water, pets, meats, and vegetables.<br />
<br />
===Infectious dose, incubation, and colonization===<br />
Since <i>C. difficile</i> is an opportunistic pathogen, the infectious dose and incubation period is unknown and widely debated. Exposure to broad spectrum antibiotics prior to infection is crucial to the pathogenesis, as <i>C. difficile</i> has a difficult time colonizing on its own, but it can be found as part of the normal gut microbiota of approximately 2-3% of the population. Once a patient has taken broad-spectrum antibiotics, <i>C. difficile</i> takes advantage of the lack of commensal bacteria in order to colonize the large intestine.<br />
<br />
===Epidemiology===<br />
====Frequency====<br />
CDAD is most often a hospital-acquired infection that causes an estimated 3 million cases of diarrhea and colitis per year. Some reports state that 28% of patients who were hospitalized tested positive for <i>C. difficile</i>. Its incidence in hospitals has risen from 30-40 per 100,000 in the 1990s to 84 per 100,000 in 2005 (4), and despite a decrease in other nosocomial infections from 2000-2009, the number of patients with CDAD discharge diagnosis more than doubled from approximately 139,000 to 336,600. In addition to this, the number of primary CDAD diagnoses more than tripled from 33,000 to 111,000. CDAD can be community-acquired, however the incidence of this is much lower than the hospital-acquired infections. The CDC’s Emerging Infections Program associated approximately 94% of CDAD diagnoses with receiving health care. Outside of the United States, the incidence of CDAD has also increased. For example, in one region of Quebec, its incidence quadrupled in 2003 to 92.2 per 100,000 populations.<br />
<br />
====Morbidity and Mortality====<br />
Though most patients with <i>C. difficile</i> can recover without specific therapy, symptoms may be particularly debilitating and drawn out. The elderly are much more susceptible to severe infection, and the mortality rate in this demographic is estimated to be as high as 25%. The disease’s mortality and morbidity seems to have increased in severity in the last decade. The CDC has reported that enteritis deaths more than doubled from 1997 to 2007 in the United States, increasing to 17,000 from about 7,000, and C difficile was associated with 14,500 of these deaths, up from 2,700 in 1999 (5). A particularly virulent strain has been traced to several outbreaks in North America, known as the NAP1/027 strain. It shows increased production of toxins A and B, antibiotic resistance, and the production of a binary toxin whose role is not yet clear, but is thought to increase the virulence of the A and B toxins.<br />
<br />
===Virulence factors===<br />
<i>C. difficile</i> expresses two toxins, toxin A (TcdA) and toxin B (TcdB), which are 2 of the largest bacterial toxins known (review). They are part of the Large Clostridial Toxin family, in which the toxins glucosylate small GTPases in the cytosol of targeted cells. Both toxins disrupt the actin cytoskeleton of fibroblasts and prevent cells from being able to regulate actin polymerization. Toxin A produces a florid inflammatory response, while B has to enterotoxin activity, but instead is a potent cytotoxin. In fact, toxin B is 10 times more potent than A in causing damage in colonic epithelial cells, which points to toxin B as the primary virulence factor. Which of the two is the primary virulence factor has been disputed and was previously thought to be toxin A, but recent evidence points towards toxin B.<br />
<br />
==Clinical features==<br />
<br />
Colonization of the intestine by <i>Clostridium difficile</i> can occur without presenting any symptoms in the host, however, infection can cause symptoms ranging from trivial diarrhea to serious manifestations of disease. General symptoms of CDAD include watery diarrhea, fever, loss of appetite, nausea, and abdominal pain/tenderness, but grossly bloody stools are unusual. Signs of more advanced disease include pseudomembranous colitis, toxic megacolon (also known as colonic distention), perforations of the colon, sepsis, and sometimes death. <br><br><br />
One of the most well recognized manifestations of the disease, pseudomembranous colitis, was first described in 1893 and is the formation of lesions within the colon that are made of a pseudomembrane of immune cells, mucus, and necrotic tissue (4). For 20% of patients with advanced CDAD: diarrhea and fluid loss are minimal, and instead, abdominal distention and bowel obstruction can lead to misdiagnosis. For other patients, signs of systemic toxicity and systemic inflammatory syndrome, including leukocytosis, rising serum lactate levels, hypotension, acute renal failure, and respiratory distress, lead to poor prognosis and high mortality rates. Fulminant colitis can lead to the need for a total colectomy, but even with this procedure, the average mortality rate at this stage of the disease is 67%, and the progression from initial symptoms to this stage can occur in as little as hours to as much as weeks.<br />
<br />
==Diagnosis==<br />
<br />
Prior to testing for <i>Clostridium difficile</i>, there are three predominate indications for the presumption of a <i>C. difficile</i> infection (CDI). Patients are most susceptible if they have received antibiotics within the last 8-12 weeks; patients are over the age of 64; patients have produced 3 or more diarrheal stools within 24 hours. The most widely accepted method used to test for CDI is a toxigenic culture involving the incubation of a fecal culture and subsequent immunoassay to test for the presence of <i>C. difficile</i> toxin A (6,7). <br />
PCR is becoming a more popular method to identify toxins A and B because of its specificity, sensitivity, and rapid results. However, physicians warn that false positives are easily obtained from asymptomatic individuals. For this reason, physicians and researchers direct only to test diarrheal stool, especially from individuals who identify with any of the three preliminary traits listed above (6).<br />
<br />
The application of a two-step technique involving an enzyme immunoassay (EIA) and a confirmatory step to detect the presence of <i>C. difficile</i> toxins in stool samples has also proven effective in clinical laboratories. The EIA is used to detect glutamate dehydrogenase (GDH); positive samples are then subject to toxigenic culturing. However, this method still requires further confirmation to determine the relative sensitivity and consistency among GDH test kits (6,7).<br />
<br />
In comparison to the EIA technique, the tissue cytotoxin assay shows higher specificity for toxin detection, but is a more complex and time intensive procedure. Tissue cytotoxin assays are considered inefficient in clinical settings (6).<br />
<br />
Repeat testing from a single stool sample is not encouraged due to the increased risk for false-positive results (6,7). Additionally, retesting a recently recovered patient may produce misleading results since <i>C. difficile</i> likely remains colonized for a period of time after CDI symptoms subside (6).<br />
<br />
==Treatment==<br />
<br />
===Non-severe cases===<br />
For non-severe cases, the first step in treatment is the cessation of the inciting antibiotic as soon as possible and only continuing concomitant antibiotics if they are prudent to the treatment of the initial infection. Oral metronidazole or vancomycin are typically administered. However, some literature points to vancomycin having increased efficacy over metronidazole (8).<br />
<br />
===Moderate to severe cases===<br />
<b>Antibiotics:</b><br><br />
For more severe cases higher, more frequent doses of vancomycin (either oral or rectal) are administered. However, rectal doses have a higher risk of producing colonic perforations and should only be administered when oral preparations are impossible for the patient.<br />
<br><br><br />
<b>Fecal Transplantation:</b><br><br />
Another method of treatment is the infusion of a purified stool substitute preparation from a healthy donor. Generally, fecal transplantation is used in cases where the patient has had multiple recurrent infections and both metronidazole and vancomycin fail. It is reasonably successful in repopulating the gut with commensal bacteria and combating antibiotic resistant CDAD (9).<br />
<br><br><br />
<b>Probiotics:</b><br><br />
Antibiotics function to alter the intestinal flora in order to produce an unfavorable environment for <i>C. difficile</i>. Some Lactobacilli, in particular, <i>S. boulardii,</i> have been shown to suppress <i>C. difficile</i> growth in hamsters. Furthermore, temporarily populating the gut with particular Lactobacilli can lower the pH of the surrounding environment and secrete degradation enzymes like proteases that place stress on the <i>C. difficile</i> population. Finally, some strains of beneficial bacteria may have the ability to protect the intestinal barrier by interfering TcdA and TcdB binding to the host gut epithelium [[#References|[10]]].<br />
<br><br><br />
<b>Immunomodulation:</b><br><br />
New research suggests that the supplementation of laboratory-derived monoclonal antibodies may have the ability to inhibit <i>C. difficile</i> colonization by stimulating toll-like receptors and upregulating expression of dendritic cells and peripheral blood monocytes [[#References|[11]]].<br />
<br><br><br />
<b>Surgery:</b><br><br />
Some severely ill patients with CDAD may require surgical intervention as a result of toxic megacolon, colonic perforations, necrotizing colitis, or infections producing systemic inflammatory responses that could potentially lead to organ failure. In these cases, diseased portions of the gastrointestinal tract are removed.<br />
<br />
==Prevention==<br />
Prevention with good hygiene habits will go a long way to protect against opportunistic pathogens like C. difficile. The main focus with C. difficile specifically should be on more conscientious antibiotic use, as broad spectrum antibiotics make patients susceptible in the first place. Restricting antibiotic use should lower the incidence of the disease and hopefully slow its growing virulence. When dealing with CDAD patients in a hospital setting, isolation of the sick, proper hand washing techniques, protective gowns and gloves, and cleaning with sodium hypochlorite are all important and effective ways to prevent outbreaks in healthcare settings. Work on a vaccine has begun, which appears to be promising, but is still far from market availability.<br />
<br />
==Host Immune Response==<br />
The pathophysiology of <i>C. difficile</i> is directly related to the host immune response to CDI. <i>C. difficile</i> colonizes in the lumen of the small intestine where it can lie dormant by means of sporulation, or it produces enterotoxins TcdA and TcdB, eliciting an inflammatory immune response. Toxin A attracts polymorphonuclear cells (PMNs) or neutrophils to the site of infection via cytokines from epithelial host cells. This influx of leukocytes as a function of the immune response increases vascular permeability, allowing TcdA and TcdB to cross the mucosal membrane. TcdB degrades colonic epithelial cells. Accumulations of leukocytes form a pseudomembrane on the lining of the colon (pseudomembranous colitis).<br><br><br />
<br />
Current research suggests that upon exposure to <i>C. difficile</i>, humans develop an adaptive immunity to TcdA and TcdB. It is estimated that approximately 60% of healthy adults exhibit IgG and IgA antibodies against C. difficile toxins. Studies suggest that adaptive immunity can begin in childhood from environmental exposure to <i>C. difficile</i>, and possibly non-toxigenic clostridial species (13, 14). Studies show that immunoglobulin A (IgA) antibody inhibits TcdA binding to epithelial cells in the colon (12). Moreover, higher levels of IgA and IgG anti-toxins were found in asymptomatic patients, as well as those who displayed minor symptoms of CDAD (13,14). <br />
==References==<br />
<br />
1. Larson HE, Price AB, Honour P, Borriello SP: <i>Clostridium difficile</i> and the aetiology of pseudomembranous colitis. <i>Lancet</i> 1978, 1: 1063-1066. <br><br />
2. Pepin J, Alary ME, Valiquette L, Raiche E, Ruel J, Godin D, Bourassa C: Increasing risk of relapse after treatment of <i>Clostridium difficile</i> colitis in Quebec, Canada. <i>Clin Infect Dis</i>. 2005 Jun 1; 40(11): 1591-7.<br><br />
3. LaMont JT, Calderwood SB, et al.: <i>Clostridium difficile</i> in adults: Clinical manifestations and diagnosis. UpToDate June 2013, Available at: http://www.uptodate.com/contents/clostridium-difficile-in-adults-clinical-manifestations-and-diagnosis.<br><br />
4. CDC. Vital Signs: Preventing Clostridium difficile Infections. <i>MMWR Morb Mortal Wkly Rep</i>. Mar 9 2012;61:157-62. [Medline].<br><br />
5. Centers for Disease Control and Prevention (CDC). Deaths from gastroenteritis double. Available at http://www.cdc.gov/media/releases/2012/p0314_gastroenteritis.html.<br><br />
6. Gould, Carolyn. CDC Commentary: Testing for <i>Clostridium difficile</i> Infection. <i>Medscape</i>. Aug 16, 2010.<br><br />
7. Cohen S., Gerding D., Johnson S., Kelly C., Loo V., McDonald L., Pepin J., Wilcox M. (2010). Clinical Practice Guidelines for <i>Clostridium difficile</i> Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America. <i>Infection Control and Hospital Epidemiology</i> 31(5):431-455. <br><br />
8. Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to <i>Clostridium difficile</i>. Gut 1986; 27: 1169.<br><br />
9. Petrof EO, Gloor GB, Vanner SJ et al. Stool substitute transplant therapy for the eradication of <i>Clostridium difficile</i> infection: ‘RePOOPulating’ the gut. <i>Microbiome</i> 2013 January; 1:3<br><br />
10. Sartor RB, LaMont JT, Probiotics for gastrointestinal diseases. UpToDate June 2013, Available at: http://www.uptodate.com/contents/probiotics-for-gastrointestinal-diseases?source=see_link&anchor=H7#H7<br><br />
11. Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against <i>Clostridium difficile</i> toxins. N Engl J Med 2010; 362:197.<br><br />
12. Kelly C. P., Pothoulakis C., Orellana J., Lamont J.T. (1992). Human colonic aspirates containing immunoglobulin A antibody to <i>Clostridium difficile</i> toxin A inhibit toxin A-receptor binding. <i>Gastroenterology</i> 102, 35-40. Pmid:1309359.<br />
<br><br />
13. Kyne L., Warny M., Qamar A., Kelly C.P. (2000). Asymptomatic carriage of <i>Clostridium difficile</i> and serum levels of IgG antibody against toxin A. <i>N Engl J Med</i> 342, 390-397. <br />
<br><br />
14. Viscidi R, Laughon BE, Yolken R, et al. Serum antibody response to toxins A and B of <i>Clostridium<br />
difficile</i>. J Infect Dis 1983;148:93–100. [PubMed: 6886489]<br />
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Created by Laura Boucher, Marrett Hild, and Lillian Flannigan, students of Tyrrell Conway at the University of Oklahoma</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Clostridium_difficile-associated_disease&diff=90058Clostridium difficile-associated disease2013-07-22T09:24:36Z<p>Daniel.E.Robinson-1: /* Description */</p>
<hr />
<div>{{Curated}}<br />
[[File:Clostridium difficile spore.gif|400px|thumb|right|Scanning electron microscope image of <i>Clostridium difficile</i>. From: Bioquell.com [http://www.bioquell.com/technology/microbiology/clostridium-difficile/]]]<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Firmicutes]]<br />
| Class = [[Clostridia]]<br />
| Order = [[Clostridiales]]<br />
| Family = [[Clostridiaceae]]<br />
| Genus = [[Clostridium]]<br />
| species = [[C. difficile]]<br />
<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=1496&lvl=3&lin=f&keep=1&srchmode=1&unlock Taxonomy] Genome: <font size="2">[http://www.ncbi.nlm.nih.gov/genome/?term=clostridium+difficile Genome]</font>'''<br />
|}<br />
<br />
===Description===<br />
<i>Clostridium difficile</i> causes pseudomembranous colitis, toxic megacolon, perforations of the colon, sepsis, and, on occasion, death. It is a Gram-positive, spore-forming rod that is an obligate anaerobe. It can be found in soil, water, feces, and the human gut. <i>C. difficile</i> is a normal inhabitant of the gut microbial community of about 1-3% of adults. The pathogenic form of <i>C. difficile</i> is transferred via the fecal-oral route as well as through spore dispersal. <i>Clostridium difficile</i>-associated disease (CDAD) was initially reported approximately 30 years ago. The CDC first recorded infections from a hyper-virulent strain in 2000 along with a marked increase in the number of CDAD infections. <i>C. difficile</i> causes disease by producing the toxins TcdA and TcdB that function to disrupt protein synthesis within the host cell. The toxins are responsible for producing symptoms such as watery diarrhea, fever, loss of appetite, nausea, and severe abdominal pain (1). Although <i>C. difficile</i> only causes about 20% of antibiotic associated colitis, standard treatments fail in about 25% of CDAD cases. Patients treated promptly typically recover. However, CDAD is notorious for recurrence after initial antibiotic treatment. 33% of patients with an infection will have a recurrence with 64% of those being within 30 days of the initial infection (2). Complications typically develop in about 11% of patients in the first recurrence. This likely promotes the growth of antibiotic resistant strains that are able to perform horizontal gene transfer between recurrences. In about 20% of patients the infection will resolve itself in 2-3 of discontinuing the inciting antibiotic. Most infections that persist are treated with a 10-14 day course of antibiotics like metronidazole, vancomycin, and rehydration therapy. In more serious cases fecal transplants and surgery can be performed [[#References|[3]]]. Patients at risk for developing CDAD include those taking antibiotics (especially broad spectrum), those taking proton pump inhibitors, GI manipulation or surgery, long term stays in hospital or clinical settings, immunocompromising conditions, and old age. The best practices for preventing infection include judicious administration of antibiotics, quarantine, hand hygiene, and the use of EPA-registered disinfectants with a sporicide (especially hypochlorite based disinfectants).<br />
<br />
==Pathogenesis==<br />
[[File:Clostridium difficile pathogenesis.jpeg|500px|thumb|right|Pathogenesis of <i>Clostridium difficile</i> and formation of pseudomembranes. From: Nature.com [http://www.nature.com/nrmicro/journal/v7/n7/fig_tab/nrmicro2164_F5.html]]]<br />
<br />
===Transmission===<br />
<i>Clostridium difficile</i> are shed in feces, and therefore this bacteria can be transmitted via the fecal-oral route. The spores can survive on almost any surface for months to years, making the pathogen very difficult to get rid of once established. The spores are resistant to many extreme environments, including high temperatures, ultraviolet light, harsh chemicals, and antibiotics. Health care settings, including patients and workers, are often the reservoirs for <i>C. difficile</i> spores. Community-acquired infections are thought to be transmitted through soil, water, pets, meats, and vegetables.<br />
<br />
===Infectious dose, incubation, and colonization===<br />
Since <i>C. difficile</i> is an opportunistic pathogen, the infectious dose and incubation period is unknown and widely debated. Exposure to broad spectrum antibiotics prior to infection is crucial to the pathogenesis, as <i>C. difficile</i> has a difficult time colonizing on its own, but it can be found as part of the normal gut microbiota of approximately 2-3% of the population. Once a patient has taken broad-spectrum antibiotics, <i>C. difficile</i> takes advantage of the lack of commensal bacteria in order to colonize the large intestine.<br />
<br />
===Epidemiology===<br />
====Frequency====<br />
CDAD is most often a hospital-acquired infection that causes an estimated 3 million cases of diarrhea and colitis per year. Some reports state that 28% of patients who were hospitalized tested positive for <i>C. difficile</i>. Its incidence in hospitals has risen from 30-40 per 100,000 in the 1990s to 84 per 100,000 in 2005 (4), and despite a decrease in other nosocomial infections from 2000-2009, the number of patients with CDAD discharge diagnosis more than doubled from approximately 139,000 to 336,600. In addition to this, the number of primary CDAD diagnoses more than tripled from 33,000 to 111,000. CDAD can be community-acquired, however the incidence of this is much lower than the hospital-acquired infections. The CDC’s Emerging Infections Program associated approximately 94% of CDAD diagnoses with receiving health care. Outside of the United States, the incidence of CDAD has also increased. For example, in one region of Quebec, its incidence quadrupled in 2003 to 92.2 per 100,000 populations.<br />
<br />
====Morbidity and Mortality====<br />
Though most patients with <i>C. difficile</i> can recover without specific therapy, symptoms may be particularly debilitating and drawn out. The elderly are much more susceptible to severe infection, and the mortality rate in this demographic is estimated to be as high as 25%. The disease’s mortality and morbidity seems to have increased in severity in the last decade. The CDC has reported that enteritis deaths more than doubled from 1997 to 2007 in the United States, increasing to 17,000 from about 7,000, and C difficile was associated with 14,500 of these deaths, up from 2,700 in 1999 (5). A particularly virulent strain has been traced to several outbreaks in North America, known as the NAP1/027 strain. It shows increased production of toxins A and B, antibiotic resistance, and the production of a binary toxin whose role is not yet clear, but is thought to increase the virulence of the A and B toxins.<br />
<br />
===Virulence factors===<br />
<i>C. difficile</i> expresses two toxins, toxin A (TcdA) and toxin B (TcdB), which are 2 of the largest bacterial toxins known (review). They are part of the Large Clostridial Toxin family, in which the toxins glucosylate small GTPases in the cytosol of targeted cells. Both toxins disrupt the actin cytoskeleton of fibroblasts and prevent cells from being able to regulate actin polymerization. Toxin A produces a florid inflammatory response, while B has to enterotoxin activity, but instead is a potent cytotoxin. In fact, toxin B is 10 times more potent than A in causing damage in colonic epithelial cells, which points to toxin B as the primary virulence factor. Which of the two is the primary virulence factor has been disputed and was previously thought to be toxin A, but recent evidence points towards toxin B.<br />
<br />
==Clinical features==<br />
<br />
Colonization of the intestine by <i>Clostridium difficile</i> can occur without presenting any symptoms in the host, however, infection can cause symptoms ranging from trivial diarrhea to serious manifestations of disease. General symptoms of CDAD include watery diarrhea, fever, loss of appetite, nausea, and abdominal pain/tenderness, but grossly bloody stools are unusual. Signs of more advanced disease include pseudomembranous colitis, toxic megacolon (also known as colonic distention), perforations of the colon, sepsis, and sometimes death. <br><br><br />
One of the most well recognized manifestations of the disease, pseudomembranous colitis, was first described in 1893 and is the formation of lesions within the colon that are made of a pseudomembrane of immune cells, mucus, and necrotic tissue (4). For 20% of patients with advanced CDAD: diarrhea and fluid loss are minimal, and instead, abdominal distention and bowel obstruction can lead to misdiagnosis. For other patients, signs of systemic toxicity and systemic inflammatory syndrome, including leukocytosis, rising serum lactate levels, hypotension, acute renal failure, and respiratory distress, lead to poor prognosis and high mortality rates. Fulminant colitis can lead to the need for a total colectomy, but even with this procedure, the average mortality rate at this stage of the disease is 67%, and the progression from initial symptoms to this stage can occur in as little as hours to as much as weeks.<br />
<br />
==Diagnosis==<br />
<br />
Prior to testing for <i>Clostridium difficile</i>, there are three predominate indications for the presumption of a <i>C. difficile</i> infection (CDI). Patients are most susceptible if they have received antibiotics within the last 8-12 weeks; patients are over the age of 64; patients have produced 3 or more diarrheal stools within 24 hours. The most widely accepted method used to test for CDI is a toxigenic culture involving the incubation of a fecal culture and subsequent immunoassay to test for the presence of <i>C. difficile</i> toxin A (6,7). <br />
PCR is becoming a more popular method to identify toxins A and B because of its specificity, sensitivity, and rapid results. However, physicians warn that false positives are easily obtained from asymptomatic individuals. For this reason, physicians and researchers direct only to test diarrheal stool, especially from individuals who identify with any of the three preliminary traits listed above (6).<br />
<br />
The application of a two-step technique involving an enzyme immunoassay (EIA) and a confirmatory step to detect the presence of <i>C. difficile</i> toxins in stool samples has also proven effective in clinical laboratories. The EIA is used to detect glutamate dehydrogenase (GDH); positive samples are then subject to toxigenic culturing. However, this method still requires further confirmation to determine the relative sensitivity and consistency among GDH test kits (6,7).<br />
<br />
In comparison to the EIA technique, the tissue cytotoxin assay shows higher specificity for toxin detection, but is a more complex and time intensive procedure. Tissue cytotoxin assays are considered inefficient in clinical settings (6).<br />
<br />
Repeat testing from a single stool sample is not encouraged due to the increased risk for false-positive results (6,7). Additionally, retesting a recently recovered patient may produce misleading results since <i>C. difficile</i> likely remains colonized for a period of time after CDI symptoms subside (6).<br />
<br />
==Treatment==<br />
<br />
===Non-severe cases===<br />
For non-severe cases, the first step in treatment is the cessation of the inciting antibiotic as soon as possible and only continuing concomitant antibiotics if they are prudent to the treatment of the initial infection. Oral metronidazole or vancomycin are typically administered. However, some literature points to vancomycin having increased efficacy over metronidazole (8).<br />
<br />
===Moderate to severe cases===<br />
<b>Antibiotics:</b><br><br />
For more severe cases higher, more frequent doses of vancomycin (either oral or rectal) are administered. However, rectal doses have a higher risk of producing colonic perforations and should only be administered when oral preparations are impossible for the patient.<br />
<br><br><br />
<b>Fecal Transplantation:</b><br><br />
Another method of treatment is the infusion of a purified stool substitute preparation from a healthy donor. Generally, fecal transplantation is used in cases where the patient has had multiple recurrent infections and both metronidazole and vancomycin fail. It is reasonably successful in repopulating the gut with commensal bacteria and combating antibiotic resistant CDAD (9).<br />
<br><br><br />
<b>Probiotics:</b><br><br />
Antibiotics function to alter the intestinal flora in order to produce an unfavorable environment for <i>C. difficile</i>. Some Lactobacilli, in particular, <i>S. boulardii,</i> have been shown to suppress <i>C. difficile</i> growth in hamsters. Furthermore, temporarily populating the gut with particular Lactobacilli can lower the pH of the surrounding environment and secrete degradation enzymes like proteases that place stress on the <i>C. difficile</i> population. Finally, some strains of beneficial bacteria may have the ability to protect the intestinal barrier by interfering TcdA and TcdB binding to the host gut epithelium (10).<br />
<br><br><br />
<b>Immunomodulation:</b><br><br />
New research suggests that the supplementation of laboratory-derived monoclonal antibodies may have the ability to inhibit <i>C. difficile</i> colonization by stimulating toll-like receptors and upregulating expression of dendritic cells and peripheral blood monocytes (11).<br />
<br><br><br />
<b>Surgery:</b><br><br />
Some severely ill patients with CDAD may require surgical intervention as a result of toxic megacolon, colonic perforations, necrotizing colitis, or infections producing systemic inflammatory responses that could potentially lead to organ failure. In these cases, diseased portions of the gastrointestinal tract are removed.<br />
<br />
==Prevention==<br />
Prevention with good hygiene habits will go a long way to protect against opportunistic pathogens like C. difficile. The main focus with C. difficile specifically should be on more conscientious antibiotic use, as broad spectrum antibiotics make patients susceptible in the first place. Restricting antibiotic use should lower the incidence of the disease and hopefully slow its growing virulence. When dealing with CDAD patients in a hospital setting, isolation of the sick, proper hand washing techniques, protective gowns and gloves, and cleaning with sodium hypochlorite are all important and effective ways to prevent outbreaks in healthcare settings. Work on a vaccine has begun, which appears to be promising, but is still far from market availability.<br />
<br />
==Host Immune Response==<br />
The pathophysiology of <i>C. difficile</i> is directly related to the host immune response to CDI. <i>C. difficile</i> colonizes in the lumen of the small intestine where it can lie dormant by means of sporulation, or it produces enterotoxins TcdA and TcdB, eliciting an inflammatory immune response. Toxin A attracts polymorphonuclear cells (PMNs) or neutrophils to the site of infection via cytokines from epithelial host cells. This influx of leukocytes as a function of the immune response increases vascular permeability, allowing TcdA and TcdB to cross the mucosal membrane. TcdB degrades colonic epithelial cells. Accumulations of leukocytes form a pseudomembrane on the lining of the colon (pseudomembranous colitis).<br><br><br />
<br />
Current research suggests that upon exposure to <i>C. difficile</i>, humans develop an adaptive immunity to TcdA and TcdB. It is estimated that approximately 60% of healthy adults exhibit IgG and IgA antibodies against C. difficile toxins. Studies suggest that adaptive immunity can begin in childhood from environmental exposure to <i>C. difficile</i>, and possibly non-toxigenic clostridial species (13, 14). Studies show that immunoglobulin A (IgA) antibody inhibits TcdA binding to epithelial cells in the colon (12). Moreover, higher levels of IgA and IgG anti-toxins were found in asymptomatic patients, as well as those who displayed minor symptoms of CDAD (13,14). <br />
==References==<br />
<br />
1. Larson HE, Price AB, Honour P, Borriello SP: <i>Clostridium difficile</i> and the aetiology of pseudomembranous colitis. <i>Lancet</i> 1978, 1: 1063-1066. <br><br />
2. Pepin J, Alary ME, Valiquette L, Raiche E, Ruel J, Godin D, Bourassa C: Increasing risk of relapse after treatment of <i>Clostridium difficile</i> colitis in Quebec, Canada. <i>Clin Infect Dis</i>. 2005 Jun 1; 40(11): 1591-7.<br><br />
3. LaMont JT, Calderwood SB, et al.: <i>Clostridium difficile</i> in adults: Clinical manifestations and diagnosis. UpToDate June 2013, Available at: http://www.uptodate.com/contents/clostridium-difficile-in-adults-clinical-manifestations-and-diagnosis.<br><br />
4. CDC. Vital Signs: Preventing Clostridium difficile Infections. <i>MMWR Morb Mortal Wkly Rep</i>. Mar 9 2012;61:157-62. [Medline].<br><br />
5. Centers for Disease Control and Prevention (CDC). Deaths from gastroenteritis double. Available at http://www.cdc.gov/media/releases/2012/p0314_gastroenteritis.html.<br><br />
6. Gould, Carolyn. CDC Commentary: Testing for <i>Clostridium difficile</i> Infection. <i>Medscape</i>. Aug 16, 2010.<br><br />
7. Cohen S., Gerding D., Johnson S., Kelly C., Loo V., McDonald L., Pepin J., Wilcox M. (2010). Clinical Practice Guidelines for <i>Clostridium difficile</i> Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America. <i>Infection Control and Hospital Epidemiology</i> 31(5):431-455. <br><br />
8. Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to <i>Clostridium difficile</i>. Gut 1986; 27: 1169.<br><br />
9. Petrof EO, Gloor GB, Vanner SJ et al. Stool substitute transplant therapy for the eradication of <i>Clostridium difficile</i> infection: ‘RePOOPulating’ the gut. <i>Microbiome</i> 2013 January; 1:3<br><br />
10. Sartor RB, LaMont JT, Probiotics for gastrointestinal diseases. UpToDate June 2013, Available at: http://www.uptodate.com/contents/probiotics-for-gastrointestinal-diseases?source=see_link&anchor=H7#H7<br><br />
11. Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against <i>Clostridium difficile</i> toxins. N Engl J Med 2010; 362:197.<br><br />
12. Kelly C. P., Pothoulakis C., Orellana J., Lamont J.T. (1992). Human colonic aspirates containing immunoglobulin A antibody to <i>Clostridium difficile</i> toxin A inhibit toxin A-receptor binding. <i>Gastroenterology</i> 102, 35-40. Pmid:1309359.<br />
<br><br />
13. Kyne L., Warny M., Qamar A., Kelly C.P. (2000). Asymptomatic carriage of <i>Clostridium difficile</i> and serum levels of IgG antibody against toxin A. <i>N Engl J Med</i> 342, 390-397. <br />
<br><br />
14. Viscidi R, Laughon BE, Yolken R, et al. Serum antibody response to toxins A and B of <i>Clostridium<br />
difficile</i>. J Infect Dis 1983;148:93–100. [PubMed: 6886489]<br />
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Created by Laura Boucher, Marrett Hild, and Lillian Flannigan, students of Tyrrell Conway at the University of Oklahoma</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=90017Rabies2013-07-22T08:44:07Z<p>Daniel.E.Robinson-1: /* References */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
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[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
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<br />
<br />
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<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=90016Rabies2013-07-22T08:43:39Z<p>Daniel.E.Robinson-1: </p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
[[Image:OULOGOBIANCO.JPEG|thumb|200px|left|University of Oklahoma Arezzo [http://cas.ou.edu/study-abroad/]]]<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89990Rabies2013-07-22T08:07:54Z<p>Daniel.E.Robinson-1: /* Structure */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The virus's envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89989Rabies2013-07-22T08:06:53Z<p>Daniel.E.Robinson-1: /* Structure */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actual sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89988Rabies2013-07-22T08:03:13Z<p>Daniel.E.Robinson-1: /* Eliminating Rabies in Dogs */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. [[#References|[6]]] Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89987Rabies2013-07-22T07:58:59Z<p>Daniel.E.Robinson-1: /* Structure */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. [[#References|[5]]]<br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89986Rabies2013-07-22T07:58:28Z<p>Daniel.E.Robinson-1: /* History and Impact */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. [[#References|[4]]]<br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89985Rabies2013-07-22T07:57:31Z<p>Daniel.E.Robinson-1: /* Taxonomy */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]| [[#References|[1]]]<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89984Rabies2013-07-22T07:56:41Z<p>Daniel.E.Robinson-1: /* Taxonomy */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|[[#References|[1]]]<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89983Rabies2013-07-22T07:56:02Z<p>Daniel.E.Robinson-1: /* Description */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus.[[#References|[2]]] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.[[#References|[3]]]<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89982Rabies2013-07-22T07:54:55Z<p>Daniel.E.Robinson-1: /* Description */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. [2] It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89981Rabies2013-07-22T07:54:37Z<p>Daniel.E.Robinson-1: /* Description */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus[2]. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89980Rabies2013-07-22T07:53:45Z<p>Daniel.E.Robinson-1: /* References */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
1 NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
2 Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
3 WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
4 Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
5 Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
6 CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89979Rabies2013-07-22T07:52:28Z<p>Daniel.E.Robinson-1: /* References */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=<br />
NCBI. Rabies Genome. Web. 22 July 2013 <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11292> <br />
<br />
Wikipedia. Rabies. 21 July 2013. Web. 22 July 2013 <http://en.wikipedia.org/wiki/Rabies><br />
<br />
WHO. Rabies fact sheet. July 2013. Web. 22 July 2013 <http://www.who.int/mediacentre/factsheets/fs099/en/><br />
<br />
Baer GM, The Natural History of Rabies, 2nd Edition. Elsevier Inc., 1975. Print.<br />
<br />
Hunt R, Virology, Chapter 20 Rabies. The Board of Trustees of the University of South Carolina. 2011. Web. 22 July 2013 <http://pathmicro.med.sc.edu/virol/rabies.htm><br />
<br />
CDC. Rabies. 15 February 2012. Web. 22 July 2013 <http://www.cdc.gov/rabies/symptoms/index.html><br />
<br />
<br />
<br />
Created by Daniel Robinson, student of the University of Oklahoma, taught by Dr. Tyrrell Conway, study abraod program, summer 2013 in Arezzo, Tuscana, Italia.</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89966Rabies2013-07-22T07:00:11Z<p>Daniel.E.Robinson-1: /* Host Immune Response */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=References=</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89961Rabies2013-07-22T06:58:42Z<p>Daniel.E.Robinson-1: /* Rabies in animals */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=Host Immune Response=<br />
=References=</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89915Rabies2013-07-22T04:49:08Z<p>Daniel.E.Robinson-1: /* Dogs */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=Rabies in animals=<br />
==Dogs==<br />
There are three stages of the disease that can be seen in dogs. The first stage, prodromal stage, is a behavioral change lasting approximately 1-3 days. the second stage, the furious stage, is an excitative and aggressive behavioral change that causes dogs to bite at anything near them. The third stage, the paralytic stage, is when neuron damage leads to paralysis and incoordination of muscles. the facial and throat muscles will eventually become paralyzed leading to drooling and inability to swallow. Death in dogs is usually caused by respiratory arrest.<br />
<br />
==Bats==<br />
==Opossums== <br />
==Foxes==<br />
==Wolves==<br />
==Other animals==<br />
<br />
=Host Immune Response=<br />
=References=</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89884Rabies2013-07-22T04:04:14Z<p>Daniel.E.Robinson-1: /* Epidemiology */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
Rabies is primarily transmitted through animal bites. Many animals can be possible vectors for the virus, however, world wide most cases are caused by dogs in poor rural areas. The most common and relevant areas in which rabies is spread through dogs are Latin America, Asia, and Africa. <br />
<br />
Between 1990 and 2004, there were 47 confirmed cases of rabies in the United States. Of those 47, 35 cases were associated with bats, and the final 12 came from dog/coyote bites. 10 of the 12 rabies cases were associated with dogs/coyotes from outside the U.S., with only 2 caused by dogs within the United States. Rabies is carried primarily through large mammals such as dogs, coyotes, raccoons, skunks, and foxes. The virus has been known to come from small rodents (woodchucks mostly), but only on rare occasions. Dogs, cats, and cattle are potential vectors for the disease in the United States. Large efforts have been put together from multiple organizations to prevent the spread of rabies from these animals using vaccinations. Bats in the U.S. have become a concern because the bats have small, very sharp teeth that may or may not be felt by people around the animals. Many bats aren't infected, but people should take caution with any contact with them. In many cases that involve rabies transmitted form bats, a fair number of people do not remember having been bitten. There have been cases of people simply handling bats that have been found in houses, barns, or in yards that became infected with the virus. <br />
<br />
Awareness of the disease is known to most people, especially when interacting with animals acting strangely or aggresively, however, symptoms of the disease may not have developed yet or go unnoticed in animals such as bats, leading to people not seeking medical attention or vaccination after coming in contact with the virus. Educating the public to the dangers of handling or being bitten by bats as well as other animals is key in making people aware of the rabies virus and how to deal with encounters with known carries.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=Rabies in animals=<br />
==Dogs==<br />
==Bats==<br />
==Opossums== <br />
==Foxes==<br />
==Wolves==<br />
==Other animals==<br />
<br />
=Host Immune Response=<br />
=References=</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89858Rabies2013-07-22T03:12:12Z<p>Daniel.E.Robinson-1: </p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Epidemiology=<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=Rabies in animals=<br />
==Dogs==<br />
==Bats==<br />
==Opossums== <br />
==Foxes==<br />
==Wolves==<br />
==Other animals==<br />
<br />
=Host Immune Response=<br />
=References=</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89856Rabies2013-07-22T03:11:31Z<p>Daniel.E.Robinson-1: /* Epidemiology */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=Rabies in animals=<br />
==Dogs==<br />
==Bats==<br />
==Opossums== <br />
==Foxes==<br />
==Wolves==<br />
==Other animals==<br />
<br />
=Host Immune Response=<br />
=References=</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89850Rabies2013-07-22T02:58:50Z<p>Daniel.E.Robinson-1: /* Disease */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
Incubation phase of the disease begins to takes place immediately after exposure. The virus binds to muscle and nerve cells at the site of the exposure through nicotinic acetylcholine receptors. Replication can occur in the muscles of the host without any signs of symptoms for a prolonged period of time. The incubation time is effected by several factors, including amount of particles exposed to and where the virus enters the host. <br />
<br />
Prodormal Phase consists of the viruses travel from the site of infection to the central nervous system. the virus travels to the spinal cord via the axons of nerves using retrograde transportation. Once at the dorsal root ganglia and spinal cord the disease then spreads to the brain. several parts of the brain are susceptible to the virus including the cerebellum, hippocampus, Purkinje cells, and Pontine nuclei. <br />
<br />
The Neurological phase includes the most prodominant and extreme symptoms of the disease. Infection of the brain causes encephalitis and neural degridation, however, it is worth noting that the virus does not cause much of a cytopathic effect. The infection of the brain will lead to coma and death. The virus may also during the neurological spread to other parts of the body via the neurons including the eyes, skin, kidneys, pancrease, and adrenals.<br />
<br />
==Epidemiology==<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=Rabies in animals=<br />
==Dogs==<br />
==Bats==<br />
==Opossums== <br />
==Foxes==<br />
==Wolves==<br />
==Other animals==<br />
<br />
=Host Immune Response=<br />
=References=</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89774Rabies2013-07-22T01:54:12Z<p>Daniel.E.Robinson-1: /* Pathogenisis */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Disease==<br />
==Epidemiology==<br />
<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=Rabies in animals=<br />
==Dogs==<br />
==Bats==<br />
==Opossums== <br />
==Foxes==<br />
==Wolves==<br />
==Other animals==<br />
<br />
=Host Immune Response=<br />
=References=</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89773Rabies2013-07-22T01:53:14Z<p>Daniel.E.Robinson-1: /* Virulance Factors */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
<br />
Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
<br />
In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
<br />
=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
<br />
<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
<br />
'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
<br />
'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
<br />
The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
<br />
'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
<br />
'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
<br />
==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
<br />
=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
<br />
==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
<br />
==Epidemiology==<br />
=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
<br />
=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
<br />
(1) Touching, Feeding, and licking on skin require no PEP.<br />
<br />
(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
<br />
(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
<br />
Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
<br />
=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
<br />
==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
<br />
=Rabies in animals=<br />
==Dogs==<br />
==Bats==<br />
==Opossums== <br />
==Foxes==<br />
==Wolves==<br />
==Other animals==<br />
<br />
=Host Immune Response=<br />
=References=</div>Daniel.E.Robinson-1https://microbewiki.kenyon.edu/index.php?title=Rabies&diff=89767Rabies2013-07-22T01:49:05Z<p>Daniel.E.Robinson-1: /* History and Impact */</p>
<hr />
<div>[[Image:rabies_virus.jpg|thumb|200px|right|''"Rhabdoviridae"'' Tranmission electron microscope picture of the viruses outer envolope. From: ppdictionary.com [http://ppdictionary.com/viruses/rabies.htm]]]<br />
=Taxonomy=<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Rhabdoviridae]]<br />
| Genus = [[Lyssavirus]]<br />
| species = [[Rabies Virus]]|<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=11270] Genome: [[Rabies Virus]] <font size="2">[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Tree&id=11292&lvl=3&p=genome&lin=f&keep=1&srchmode=1&unlock]</font>'''<br />
|}<br />
<br />
=Description=<br />
Rabies (derived from Latin word <i>Rabere</i>, meaning 'Rage') is a viral disease caused by <i>Lyssavirus</i> rabies virus. It is a neurotropic virus, capable of invasive infection of the central nervous system. The disease is extremely lethal to those unfortunate enough to show symptoms of the infection. The primary transmission of the virus to humans occurs through dog bites and scratches. The numbers vary widely form country to country, however, it is estimated that 55,000 people die per year from the rabies virus in Asia and Africa . The disease can be dramatic in its appearance as with many animals the disease is known to cause hyperactivity and sporadic behavior while becoming aggressive to things around them and eventually succumbing to paralysis of muscles.<br />
<br />
=History and Impact=<br />
[[Image: Middle_Ages_rabid_dog.jpg|thumb|200px|right|''"middle ages rabid dog"'' A woodcut from the Middle Ages showing a rabid dog. From: Wikipedia.com [http://en.wikipedia.org/wiki/File:Middle_Ages_rabid_dog.jpg#file]]]<br />
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Rabies is a very old disease having originated before much of written history. The relationship between dogs and humans is shaped and altered greatly by the this disease originating from mad and crazed animals. Some of the oldest texts that are linked to rabies come from 2300 BC Eshunna, a Babylonian city, known for heavily fining people who's dogs bit others and lead to their death. Through out the Greek and Roman Empires rabies was well known and even widespread. The Greek philosophers even wrote that "dogs suffer from the madness." (Aristotle 400B.C.). It was the Romans who first described the saliva from rabid dogs as '<i>virus</i>' which is Latin for poison. A Roman physician by the name of Celsus had a treatment for wounds caused by rabid animals that remained widely accepted from 45 A.D. till the 1900's. Many physicians in history have described the symptoms of rabies, came up with cures and temporary ailments for the sick. The first case of rabies reported in the Americas was in Mexico by a priest in 1703. The disease swept the entire world slowly over centuries until it was noted on every continent on the globe except Antartica. <br />
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In 1804 a German scientist by the name of Zinke begins conducting experiments using infected saliva on various animals, confirming that the disease does come from other infected animals. The key turning point in history for rabies comes in the 1880's when Louis Pasteur, a chemist, and his assistant, scientist, and physician, Emile Roux begin research for a cure to rabies. By 1883, the two have created was is to be the first vaccine against the disease, but the real test to prove to the public that it works comes in 1885 when a nine year old Joseph Meister is bitten by a rabid dog and brought to Pasteur who puts his career on the line by testing the new vaccine for the first time. The vaccine was a success and young Joseph Meister became the first person to be successfully treated for the disease. Pasteur being a chemist not a doctor is given immediate praise and hailed as a hero. This new vaccine is still used to this day and is still the standard treatment of rabies. The vaccine also works towards animals such as dogs leading to the campaigns of vaccinating pets to prevent the spread of disease.<br />
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=Virology=<br />
==Structure==<br />
[[Image: vsv_virion.jpg|thumb|200px|right|''"<i>Rhabdoviruses</i>"'' Structure of the virus particle From: Virology.ws [http://www.virology.ws/2010/02/23/architecture-of-a-bullet-shaped-virus/]]]<br />
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<i>Rhabdoviruses</i> are negative stand RNA virues, having only a single strand of RNA genome that reads the opposite of the coding strand needed to produce protiens. The virus also contains and uses its own RNA dependent RNA polymerase to make the coding strand necessary for protein production. The overall shape of the virus is 'rod shaped', with one flat end and the other rounded, giving a bullet appearance. The average diameter is roughly 100 nanometers and a length of approximately 400 nanometers, however, the actually sizes of the virus particles do vary some. The viruses envelope consists of host plasma membrane Phospholipid bi-layers. The virus contains and codes for five proteins. <br />
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'G' Surface protein is a glycoprotein that forms a trimer. there excists about 1200 'G' proteins or 400 trimers per virus particle. The protein has a N-terminal signal sequence and is a transmambrane, crossing both phospholipid bi-layers. The 'G' proteins function is to bind to cell receptors on the surface of target cells, such as neurons in the central nervous system. This protein is also the target of antibodies and immunoglobulins from the adaptive immune response. There are three N-glyosidicaly attached sugar chains to the G protein. The virus enters the hosts cells cytoplasm through the endocytic pathway. When the virus becomes engulfed, the pH will drop, however, the sugar chain becomes stabilized at pH 6.1 and allows for the hydrophobic regions of the molecules to become embedded into the membrane of the hosts cell.<br />
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'M' Matrix protein is peripheral membrane protein that can be found in the inner membrane of the virus. The function of this protein not fully understood, but it is thought to act as a communicator between the 'G' protein and the nucleocapsid. <br />
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The Nucleocapsid is a striated structure inside the viral particle and takes on a helical shape. This structure consists of two proteins, the 'N' Nucleoprotein, and collectively the 'L' Large protein and the 'NS' Nonstructural or sometimes known as 'P' Phosphol protein.<br />
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'N' Nucleoprotein is a structural protein whose function is to cover the RNA for protection and allow for its transcription. <br />
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'P' Phosho Protein, having both the 'L' and 'NS', makes the RNA dependent RNA polymerase. The function of this complex is to generate the coding strand of the RNA contained in the virus perticle. This polymerase is approximately 240 kiloDalton's and roughly 60% of the viral RNA genome.<br />
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==Replication==<br />
How the virus binds to a target via its receptors is not completely understood, but it is suggested through experimentation that the phospholipids, more specifically the phosphatidyl serine is involved in this process. Transcription occurs after the virus has been engulfed through endocytosis. The nucleocapsid is still contained within the virus capsule and now needs to reach cellular ribosomes in order to be transcribed. Once the pH inside the endosome drops, the membranes of the virus and endosome fuse, and the nucleocapsid is released into the cytoplasm. Multiple copies of the RNA are synthesized from the negative strand. Transcription takes place with the RNA being processed into five mRNA strand that make up some of the proteins encoded by the viral genome. Before the mRNA can be translated it is first capped, methylated, and polyadenylated. After translation of the mRNA into proteins, 'G' proteins is incorporated into the membrane of the endoplasmic reticulum and is transported to the cells surface via the golgi apparatus. Patches of these 'G' proteins then associate with 'M' proteins. A new nucleocapsid forms inside the cytoplasm from the synthesized proteins 'N','L', and 'P'. Formation of the nucleocapsid associates with the 'M' protein at the membrane budding off of the membrane with the new virus particle complete.<br />
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=Pathogenisis=<br />
==Transmission==<br />
Infection to humans usually occurs through a bite or scratch from an infected animal. Saliva from infected animals, as well as humans, can cause rabies when in contact with mucous tissues or recent skin wounds. Inhalation of aerosols containing virus particles as well as transplant of viral infected tissues have also been documented as possible forms of transmission. Many animals have the potential to carry the virus, but the most common source is dogs. Bats are a common source in the Americas. Other animals known to carry the disease include foxes, raccoons, skunks, jackals, and mongooses. Human to human infection through bite or scratch is hypothetically possible, but has never been confirmed.<br />
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==Incubation==<br />
The rabies virus has a fairly long incubation period in comparison to many other viruses. Average time from inoculation to symptoms is approximately 1-3 months, however, cases have been reported of symptoms showing in as little as 1 week, and as long as 6 years.<br />
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==Epidemiology==<br />
==Virulance Factors==<br />
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=Diagnosis=<br />
No tests are currently available prior to symptoms to test for the viruses presence. The Virus can be confirmed via intra vitam and post mortem procedures that detect the virus as a whole, the viral antigens from host production, or the nucleic acids of the virus from infected tissues. Examples of these detection methods include reverse transcription polymerase chain reaction (RT PCR) test kits, negri bodies found in neuron cells, use of florescent tagged antibodies in infected tissues, live viral culturing (including WI-38, BHK-21, or CER), and several serological tests (including MNT, RFFIT, and EIA). Some of the tests can even be combined such as using IF on live tissue cultures to test for presence of rabies antigens.<br />
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=Treatment=<br />
Post-Exposure Prophylaxis is the main course of action needed to prevent rabies from causing disease. The type of interaction with a suspected infected animals dictates the specific action necessary for treatment and is generally understood in three categories. <br />
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(1) Touching, Feeding, and licking on skin require no PEP.<br />
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(2) Nibbling of uncovered skin, minor scratches with no bleeding may require immediate local treatment of wound and vaccination is recommended as a precautionary measure to prevent the disease.<br />
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(3) 1 or more trans-dermal bites or scratches or lick on broken skin, as well as contact of mucous membrane with saliva will require local treatment of wound(s), vaccination, and likely use of rabies immunoglobulin to prevent and counteract to virus. <br />
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Physical and chemical methods of cleaning wounds are recommended as effective methods of removal of the virus. Some examples of these methods include Rinsing the wound with water, soap, detergent, and providone iodine.<br />
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=Prevention=<br />
[[Image:rabies_2012.jpg|thumb|200px|right|''"Rabies Distribution"'' Data from the World Health Organization (WHO) 2012. From: nathnac.org [http://www.nathnac.org/travel/factsheets/rabies1.htm]]]<br />
==Eliminating Rabies in Dogs==<br />
The disease is absolutely preventable with the use of the vaccine. Do to the cost of health care, the best way to prevent the spread of rabies to humans is by eliminating rabies in animal (especially dog) populations. Vaccinating pets and controlling the wild life that comes in cantact with them are good preventative measures. Spade or neuter pets will help to decrease the number of stray animals and reporting any sick or stray animals to local animal control will also prevent the spread of rabies in near by areas. Rabies has been completely eradicated from a few countries, but there have been recent increases of the disease in Asia, Africa, and Latin America suggesting that the virus is becoming a re-emerging pathogen. By preventing rabies in animals such as dogs, the number of people needing Post-exposure prophylaxis treatment is significantly diminished.<br />
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==Preventative Immunizations in People==<br />
Vaccinations can be used as pre-exposure preventative measures of immunization. People spending a lot of time in rural outdoor areas, especially travelers to high risk regions are recommended for vaccination. High risk jobs such as laboratory scientist working around the rabies virus, jobs that require working around bats, carnivores, and other mammals known to carry rabies in high risk areas are also recommended for pre-exposure vaccination. Children are at a higher risk of becoming infected because of close contact and play with animals. Children may be bitten and not tell others about bites they may have received and are recommended to receive vaccination.<br />
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=Rabies in animals=<br />
==Dogs==<br />
==Bats==<br />
==Opossums== <br />
==Foxes==<br />
==Wolves==<br />
==Other animals==<br />
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=Host Immune Response=<br />
=References=</div>Daniel.E.Robinson-1