https://microbewiki.kenyon.edu/api.php?action=feedcontributions&user=Danielle.L.Vinnedge-1&feedformat=atommicrobewiki - User contributions [en]2024-03-29T15:06:22ZUser contributionsMediaWiki 1.39.6https://microbewiki.kenyon.edu/index.php?title=EBOV&diff=91636EBOV2013-07-25T09:21:04Z<p>Danielle.L.Vinnedge-1: /* Treatment */</p>
<hr />
<div>{{Curated}}<br />
<br />
[[Image: ebola4.jpeg |thumb|400px|right| The Ebola virus micrograph. From: http://www.thesundaytimes.co.uk/sto/culture/books/non_fiction/article1133688.ece]]<br />
==<b>Etiology</b>==<br />
===Taxonomy===<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Filoviridae]]<br />
| Genus = [[Ebolavirus]]<br />
| Species = [[Zaire ebolavirus]] |<br />
<br />
===Description===<br />
The Ebola virus was first detected in 1976 in the Democratic Republic of the Congo near the Ebola river; hence, the virus was named after the location of origin. (CDC). <br />
It is a negative-sense, non-segmented, enveloped RNA virus belonging to the Filoviridae family. There are five identified species of the virus, each named after the region they were localized. The Zaire, Sudan, Ivory Coast, and Bundibugyo affect humans; whereas, the Reston virus only causes disease in non-human primates. The natural reservoir of the virus remains unknown. However, non-human primates and fruit bats, of <i>Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata </i> species, are considered zoonotic reservoirs of the virus. The Reston virus was isolated from cynomolgous monkeys imported from the Philippines to the United States and Italy. <br />
Infection is characterized by septic shock, hemorrhagic fever, coagulation of cells, and tissue necrosis. Some individuals are able to recover, but most do not survive. It remains unknown as to why some survive and others die. It is classified as a level 4 disease by the CDC. [[#References|[1]]] [[#References|[2]]] [[#References|[3]]]<br />
<br />
==<b>Pathogenesis</b>==<br />
<br />
===Transmission===<br />
There are two types of exposures that contribute to acquiring the Ebola virus. The first, primary exposure, is due to travel in an ebola endemic area. The second mode of transmission is contact with bodily fluids of an infected host as well as utilizing unsterilized hospital equipment that came in contact with the virus. [[#References|[4]]]<br />
<br />
===Infectious dose and incubation===<br />
Upon invasion of host cells, the virus typically presents a 2-21 day incubation period. The infectious dose is very low; 1-10 aerosolized particles are sufficient to cause disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
As indicated by the chart provided by The World Health Organization, Ebola virus mainly affects regions in Africa. However, Reston strain did affect monkeys in the United States and Italy when they were imported from Italy. The Zaire virus outbreak seems to be the most predominant. The chart depicts outbreaks in Africa up until May 2012. <br />
<br />
<br />
<br />
[[Image: chart-1.jpeg |thumb|400px|center| Record of Ebola hemorrhagic outbreaks as of May 2012. From: http://www.who.int/mediacentre/factsheets/fs103/en/]]<br />
<br />
===Virulence Factors===<br />
EBOV viral strand contains seven genes encompassed in a 19 kb genome. Gene products produced are a glycoprotein (GP) virion envelope, nucleoprotein (NP), nonstructural proteins VP30 and VP35, matrix proteins VP24 and VP40, and a viral polymerase. VP35 and the GP are the major contributors to the onset of disease. [[#References|[9]]]<br />
<br />
====VP35====<br />
Previous studies demonstrate VP35 is protein virulence factor that serves as a cofactor for viral RNA polymerase complex, RNAi silencing suppressor and for viral assembly. In addition, VP35 promotes immune lapse by blocking antiviral signaling pathways and by denaturing the type I IFN system. Thus, the protein is able to replicate RNA and evade host cells. EBOV VP35 IID interferes with type I interferons (IFNs) and IFNα/β upon the engagement of PRRs and PAMPs, which in a normal immune response, produce the necessary type I IFNs. Transcription factors (IRF)3, IRF-7, and NKκ stimulate the IFNα/β to release IFNα and IFNβ. IFNα and IFNβ in turn stimulate antiviral activity genes like MHC class I and PKR. By activating these genes, we can reduce viral replication and in turn reduce the spread of infection. Inhibition of IFNα/β indirectly affects dendritic cell maturation because IFN production is reduced. [[#References|[7]]] [[#References|[9]]] <br />
<br />
The mechanism by which VP35 binds its RNA remains uncertain. However, structural studies of the protein reveal that it is comprised of two subdomains. The alpha subdomain is composed of a four helix bundle and the beta domain is composed of four antiparallel beta strands, alpha helix, and a polyproline helix. Furthermore, the VP35 contains two basic patches, one in the beta sheet subdomain and the other in the alpha helical subdomain. The beta sheet domain has Arg305, Arg12, and Lys309 that allow for further immune suppression. VP35 is also characterized by an “end cap” that is composed of hydrophobic Phe239 and Ile340; this hydrophobic area allows RNA to bind to VP35 IID; in turn, antagonize antiviral signaling pathways. The N-terminus of the protein is utilized to allow NP and VP40 binding, the formation of viral polymerase complex, PKR, and RNAi silencing suppression. Scientists believe that perhaps preventing the adherence of VP35, the ebola virus can be avoided in host cells. [[#References|[7]]] [[#References|[9]]]<br />
<br />
====GP====<br />
The glycoprotein (GP) envelope around EBOV allows the virus to adhere and fuse with host cells. Studies conducted in the past suggest that the GP holds a trimeric form with GP1 and GP2 (which are linked by a disulfide bond). A neutralizing antibody, KZ52, detected in a human EBOV survivor was utilized to crystalize the structure of the GP+antibody. GP1 attributes allow EBOV to attach to host cells. It is composed of a base, head, and glycan cap. The base forms a clamp that allows the stabilization of GP2 pre-fusion conformation. The GP2 subunit attributes allow EBOV to fuse with host cells. GP1 forms a chalice that is supported by GP2 whilst a glycan cap and mucin-like domain protect the receptor binding site. The neutralizing antibody detects proteins on the chalice base causing it to bind to GP1 via Van der Waals forces. EBOV then makes it’s entry into host cells via endocytosis. [[#References|[10]]]<br />
<br />
==<b>Clinical features</b>==<br />
===Symptoms===<br />
Ebola nfection is characterized by the onset of malaise, fever, myalgia, diarrhea, vomiting, and headaches. As the disease progresses, gastrointestinal bleeding, lymphopenia, neutrophilia, maculopapular rash, conjuctivitis, along with external bleeding may occur. Some patients are able to recover from the infection; however, it remains unknown as to why some recover and others die. Survivors are typically left with a range of maladies that include fatigue, bulimia, hearing loss, tinnitus, arthralgias, orchitis, and suppurative parotitis. [[#References|[4]]] [[#References|[9]]]<br />
[[Image: ebolavictim.jpeg |thumb|400px|right| Ebola patient. <br /> From: http://news.bbc.co.uk/2/hi/africa/567974.stm]]<br />
<br />
===Mortality===<br />
Mortality rates are between 50-90%. It is possible to survive the Ebola virus; however, statistics suggest the EBOV is more fatal than the other species of the ebola virus. Epidemiological studies indicate that the Zaire species is predominant in infecting human hosts. [[#References|[9]]]<br />
<br />
==<b>Diagnosis</b>==<br />
Typically, clinical diagnosis can only be made after the first few days of symptoms because the early symptoms could have been caused by many other factors. <br />
Laboratory tests such as, enzyme-linked immunosorbent assay (ELISA), serum neturalization tests, antigen detection tests, virus isolation, and a reverse transcriptase polymerase chain reaction (RT-PCR) definitively allow the detection of the ebola virus in a patient. Immunohistochemistry testing and PCR can be conducted in patients that did not survive the disease. These tests are conducted under maximum biological containment conditions. [[#References|[1]]] [[#References|[2]]] [[#References|[3]]]<br />
<br />
==<b>Treatment</b>==<br />
Currently, vaccines and antivirals are not available to treat EBOV. Patients are provided supportive treatment that includes attention to: replacement of fluids, electrolytes, constant monitoring of blood pressure and oxygen levels, nutrition and comfort. [[#References|[1]]]<br />
<br />
==<b>Prevention</b>==<br />
Infected individuals are quarantined in a facility that entails the necessary safety measures authored by the CDC and WHO. Health care professionals dress in biohazard suits before coming in contact with a patient. If biohazard suits are not available, protective clothing, goggles, gloves, and mask should be worn. To reduce the risk of acquiring the Ebola virus, avoid travelling to endemic areas in Africa. In addition, avoid consuming bush meats that are sold on street markets. Wear gloves, protective clothing, and a mask when caring for an ill that may possibly be affect with ebola. Also avoid coming in contact with an infected corpse. Wash hands frequently when travelling; if no soap is available, rub hands with 60% alcohol. Take careful precautions before coming in contact with the fluids of non-human primates from Africa or the Philippines. [[#References|[1]]] [[#References|[5]]] [[#References|[6]]]<br />
[[Image: ebov.jpeg |thumb|400px|left| Depiction of health care professionals dressed in biohazard suits. From: http://foxfromzim.files.wordpress.com/2010/05/ebola.jpeg]]<br />
<br />
==<b>Host Immune Response</b>==<br />
The lack of infected human tissue prevents the pathologic study of EBOV; thus, studies conducted in cynomolgus monkeys only suggest the possible mechanisms of infection in humans. <br />
<br />
The GP gives EBOV access to host cells by allowing the transfer of the viral genome into macrophages. Infected cells may trigger antigen-specific immune responses to prevent viral replications; however, if immune responses fail, death occurs 1-2 weeks after infection. The present GP allows the virus to conveniently adhere to cell surface lectins in addition to a variety of other molecules. ZEBOV impairs the function of macrophages and dendritic cells in the immune response system. These antigen presenting cells are able to trigger inflammation and coagulation; however, they lack the ability to prevent RNA replication in the host cells.<br />
<br />
RNA binds to PRRs on the macrophage surface to trigger cytoplasmic signaling to cause the migration of vasoactive molecules like cytokines (TNF-alpha and IL-1beta), chemokines (MIP-1alpha), and nitric oxide. The release of these molecules causes additional macrophages and monocytes to migrate to the infected cell. Neutrophils are then released to aid the present macrophages. Lipid mediators trigger the inflammation response, which causes vasodilation, increased endothelial permeability, and expression of adhesion molecules to trap leukoctyes. This allows the virus to skillfully invade host immune cells to cause hypotension and septic shock. In addition, the binding of coagulation factors to cells excites intracellular signaling pathways by phosphorylating cytoplasmic TF tails; this hinders macrophage function. <br />
<br />
Infected dendritic cells fail to express costimulatory molecules, MHC, and thus, prevent differentiation of lymphocytes. ZEBOV does not invade lymphocytes; however, the presence of the virus does initiate cell apoptosis causing lymphopenia and thus, septic shock. Natural killer cells, CD4 and CD8 cells are the prominent cell types affected during the course of the disease. Typically, these cells play a critical role in preventing viral replication. [[#References|[8]]]<br />
<br />
==<b>References</b>==<br />
1 [http://www.who.int/mediacentre/factsheets/fs103/en/ WHO Fact Sheet on Ebola haemorrhagic fever]<br />
<br><br />
2 [http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ebola-eng.php Public Health Agency of Canada Ebola virus- Pathogen Safety Data Sheets]<br />
<br><br />
3 [http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola/qa.htm CDC Questions and Answers about Ebola Hemorrhagic fever]<br />
<br><br />
4 [http://emedicine.medscape.com/article/216288-overview#aw2aab6b2b5 MedScape Ebola Virus] <br />
<br><br />
5 [http://www.mayoclinic.com/health/ebolavirus/DS00996/DSECTION=tests%2Dand%2Ddiagnosis Mayo Clinic Ebola Virus and Marburg Virus]<br />
<br><br />
6 [http://www.nlm.nih.gov/medlineplus/ency/article/001339.htm Medline Plus Ebola hemorrhagic fever]<br />
<br><br />
7 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061251/ Daisy W Leung, Kathleen C Prins, Christopher F Basler, and Gaya K Amarasinghe. Ebolavirus VP35 is a multifunctional virulence factor. US National Library of Medicine and National Institute of Health]<br />
<br><br />
8 [http://www.ncbi.nlm.nih.gov.ezproxy.lib.ou.edu/pubmed/15896665 Bray, Mike and Thomas W. Geisbert. Ebola virus: The role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever. US National Library of Medicine and National Institute of Health]<br />
<br><br />
9 [http://jvi.asm.org/content/77/18/9733 Sullivan, Nancy, Zhi-Yong Yang, and Gary J. Nabel. Ebola Virus Pathogenesis: Implications for Vaccines and Therapies. American Society for Microbiology]<br />
<br><br />
10 [http://www.ncbi.nlm.nih.gov/pubmed/20198110 JE, Lee and Saphire EO. Ebolavirus glycoprotein structure and mechanism of entry. US National Library of Medicine and National Institutes of Health]<br />
<br><br />
<br><br />
<br />
[[Image: OUA.png |thumb|400px|right| OU Microbiology in Arezzo, Italy]]<br />
<br />
Created by Bhumi Patel, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=EBOV&diff=91632EBOV2013-07-25T09:19:09Z<p>Danielle.L.Vinnedge-1: </p>
<hr />
<div>{{Curated}}<br />
<br />
[[Image: ebola4.jpeg |thumb|400px|right| The Ebola virus micrograph. From: http://www.thesundaytimes.co.uk/sto/culture/books/non_fiction/article1133688.ece]]<br />
==<b>Etiology</b>==<br />
===Taxonomy===<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Filoviridae]]<br />
| Genus = [[Ebolavirus]]<br />
| Species = [[Zaire ebolavirus]] |<br />
<br />
===Description===<br />
The Ebola virus was first detected in 1976 in the Democratic Republic of the Congo near the Ebola river; hence, the virus was named after the location of origin. (CDC). <br />
It is a negative-sense, non-segmented, enveloped RNA virus belonging to the Filoviridae family. There are five identified species of the virus, each named after the region they were localized. The Zaire, Sudan, Ivory Coast, and Bundibugyo affect humans; whereas, the Reston virus only causes disease in non-human primates. The natural reservoir of the virus remains unknown. However, non-human primates and fruit bats, of <i>Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata </i> species, are considered zoonotic reservoirs of the virus. The Reston virus was isolated from cynomolgous monkeys imported from the Philippines to the United States and Italy. <br />
Infection is characterized by septic shock, hemorrhagic fever, coagulation of cells, and tissue necrosis. Some individuals are able to recover, but most do not survive. It remains unknown as to why some survive and others die. It is classified as a level 4 disease by the CDC. [[#References|[1]]] [[#References|[2]]] [[#References|[3]]]<br />
<br />
==<b>Pathogenesis</b>==<br />
<br />
===Transmission===<br />
There are two types of exposures that contribute to acquiring the Ebola virus. The first, primary exposure, is due to travel in an ebola endemic area. The second mode of transmission is contact with bodily fluids of an infected host as well as utilizing unsterilized hospital equipment that came in contact with the virus. [[#References|[4]]]<br />
<br />
===Infectious dose and incubation===<br />
Upon invasion of host cells, the virus typically presents a 2-21 day incubation period. The infectious dose is very low; 1-10 aerosolized particles are sufficient to cause disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
As indicated by the chart provided by The World Health Organization, Ebola virus mainly affects regions in Africa. However, Reston strain did affect monkeys in the United States and Italy when they were imported from Italy. The Zaire virus outbreak seems to be the most predominant. The chart depicts outbreaks in Africa up until May 2012. <br />
<br />
<br />
<br />
[[Image: chart-1.jpeg |thumb|400px|center| Record of Ebola hemorrhagic outbreaks as of May 2012. From: http://www.who.int/mediacentre/factsheets/fs103/en/]]<br />
<br />
===Virulence Factors===<br />
EBOV viral strand contains seven genes encompassed in a 19 kb genome. Gene products produced are a glycoprotein (GP) virion envelope, nucleoprotein (NP), nonstructural proteins VP30 and VP35, matrix proteins VP24 and VP40, and a viral polymerase. VP35 and the GP are the major contributors to the onset of disease. [[#References|[9]]]<br />
<br />
====VP35====<br />
Previous studies demonstrate VP35 is protein virulence factor that serves as a cofactor for viral RNA polymerase complex, RNAi silencing suppressor and for viral assembly. In addition, VP35 promotes immune lapse by antagonizing antiviral signaling pathways and by denaturing the type I IFN system. Thus, the protein is able to replicate RNA and evade host cells. EBOV VP35 IID interferes with type I interferons (IFNs) and IFNα/β upon the engagement of PRRs and PAMPs, which in a normal immune response, produce the necessary type I IFNs. Transcription factors (IRF)3, IRF-7, and NKκ stimulate the IFNα/β to release IFNα and IFNβ. IFNα and IFNβ in turn stimulate antiviral activity genes like MHC class I and PKR. By activating these genes, we can reduce viral replication and in turn reduce the spread of infection. Inhibition of IFNα/β indirectly affects dendritic cell maturation because IFN production is reduced. [[#References|[7]]] [[#References|[9]]] <br />
<br />
The mechanism by which VP35 binds its RNA remains uncertain. However, structural studies of the protein reveal that it is comprised of two subdomains. The alpha subdomain is composed of a four helix bundle and the beta domain is composed of four antiparallel beta strands, alpha helix, and a polyproline helix. Furthermore, the VP35 contains two basic patches, one in the beta sheet subdomain and the other in the alpha helical subdomain. The beta sheet domain has Arg305, Arg12, and Lys309 that allow for further immune suppression. VP35 is also characterized by an “end cap” that is composed of hydrophobic Phe239 and Ile340; this hydrophobic area allows RNA to bind to VP35 IID; in turn, antagonize antiviral signaling pathways. The N-terminus of the protein is utilized to allow NP and VP40 binding, the formation of viral polymerase complex, PKR, and RNAi silencing suppression. Scientists believe that perhaps preventing the adherence of VP35, the ebola virus can be avoided in host cells. [[#References|[7]]] [[#References|[9]]]<br />
<br />
====GP====<br />
The glycoprotein (GP) envelope around EBOV allows the virus to adhere and fuse with host cells. Studies conducted in the past suggest that the GP holds a trimeric form with GP1 and GP2 (which are linked by a disulfide bond). A neutralizing antibody, KZ52, detected in a human EBOV survivor was utilized to crystalize the structure of the GP+antibody. GP1 attributes allow EBOV to attach to host cells. It is composed of a base, head, and glycan cap. The base forms a clamp that allows the stabilization of GP2 pre-fusion conformation. The GP2 subunit attributes allow EBOV to fuse with host cells. GP1 forms a chalice that is supported by GP2 whilst a glycan cap and mucin-like domain protect the receptor binding site. The neutralizing antibody detects proteins on the chalice base causing it to bind to GP1 via Van der Waals forces. EBOV then makes it’s entry into host cells via endocytosis. [[#References|[10]]]<br />
<br />
==<b>Clinical features</b>==<br />
===Symptoms===<br />
Ebola nfection is characterized by the onset of malaise, fever, myalgia, diarrhea, vomiting, and headaches. As the disease progresses, gastrointestinal bleeding, lymphopenia, neutrophilia, maculopapular rash, conjuctivitis, along with external bleeding may occur. Some patients are able to recover from the infection; however, it remains unknown as to why some recover and others die. Survivors are typically left with a range of maladies that include fatigue, bulimia, hearing loss, tinnitus, arthralgias, orchitis, and suppurative parotitis. [[#References|[4]]] [[#References|[9]]]<br />
[[Image: ebolavictim.jpeg |thumb|400px|right| Ebola patient. <br /> From: http://news.bbc.co.uk/2/hi/africa/567974.stm]]<br />
<br />
===Mortality===<br />
Mortality rates are between 50-90%. It is possible to survive the Ebola virus; however, statistics suggest the EBOV is more fatal than the other species of the ebola virus. Epidemiological studies indicate that the Zaire species is predominant in infecting human hosts. [[#References|[9]]]<br />
<br />
==<b>Diagnosis</b>==<br />
Typically, clinical diagnosis can only be made after the first few days of symptoms because the early symptoms could have been caused by many other factors. <br />
Laboratory tests such as, enzyme-linked immunosorbent assay (ELISA), serum neturalization tests, antigen detection tests, virus isolation, and a reverse transcriptase polymerase chain reaction (RT-PCR) definitively allow the detection of the ebola virus in a patient. Immunohistochemistry testing and PCR can be conducted in patients that did not survive the disease. These tests are conducted under maximum biological containment conditions. [[#References|[1]]] [[#References|[2]]] [[#References|[3]]]<br />
<br />
==<b>Treatment</b>==<br />
Currently, vaccines and antivirals are not available to treat EBOV. Patients are provided supportive treatment that includes attention to: Replacement of fluids, electrolytes, constant monitoring of blood pressure and oxygen levels, nutrition and comfort. [[#References|[1]]]<br />
<br />
==<b>Prevention</b>==<br />
Infected individuals are quarantined in a facility that entails the necessary safety measures authored by the CDC and WHO. Health care professionals dress in biohazard suits before coming in contact with a patient. If biohazard suits are not available, protective clothing, goggles, gloves, and mask should be worn. To reduce the risk of acquiring the Ebola virus, avoid travelling to endemic areas in Africa. In addition, avoid consuming bush meats that are sold on street markets. Wear gloves, protective clothing, and a mask when caring for an ill that may possibly be affect with ebola. Also avoid coming in contact with an infected corpse. Wash hands frequently when travelling; if no soap is available, rub hands with 60% alcohol. Take careful precautions before coming in contact with the fluids of non-human primates from Africa or the Philippines. [[#References|[1]]] [[#References|[5]]] [[#References|[6]]]<br />
[[Image: ebov.jpeg |thumb|400px|left| Depiction of health care professionals dressed in biohazard suits. From: http://foxfromzim.files.wordpress.com/2010/05/ebola.jpeg]]<br />
<br />
==<b>Host Immune Response</b>==<br />
The lack of infected human tissue prevents the pathologic study of EBOV; thus, studies conducted in cynomolgus monkeys only suggest the possible mechanisms of infection in humans. <br />
<br />
The GP gives EBOV access to host cells by allowing the transfer of the viral genome into macrophages. Infected cells may trigger antigen-specific immune responses to prevent viral replications; however, if immune responses fail, death occurs 1-2 weeks after infection. The present GP allows the virus to conveniently adhere to cell surface lectins in addition to a variety of other molecules. ZEBOV impairs the function of macrophages and dendritic cells in the immune response system. These antigen presenting cells are able to trigger inflammation and coagulation; however, they lack the ability to prevent RNA replication in the host cells.<br />
<br />
RNA binds to PRRs on the macrophage surface to trigger cytoplasmic signaling to cause the migration of vasoactive molecules like cytokines (TNF-alpha and IL-1beta), chemokines (MIP-1alpha), and nitric oxide. The release of these molecules causes additional macrophages and monocytes to migrate to the infected cell. Neutrophils are then released to aid the present macrophages. Lipid mediators trigger the inflammation response, which causes vasodilation, increased endothelial permeability, and expression of adhesion molecules to trap leukoctyes. This allows the virus to skillfully invade host immune cells to cause hypotension and septic shock. In addition, the binding of coagulation factors to cells excites intracellular signaling pathways by phosphorylating cytoplasmic TF tails; this hinders macrophage function. <br />
<br />
Infected dendritic cells fail to express costimulatory molecules, MHC, and thus, prevent differentiation of lymphocytes. ZEBOV does not invade lymphocytes; however, the presence of the virus does initiate cell apoptosis causing lymphopenia and thus, septic shock. Natural killer cells, CD4 and CD8 cells are the prominent cell types affected during the course of the disease. Typically, these cells play a critical role in preventing viral replication. [[#References|[8]]]<br />
<br />
==<b>References</b>==<br />
1 [http://www.who.int/mediacentre/factsheets/fs103/en/ WHO Fact Sheet on Ebola haemorrhagic fever]<br />
<br><br />
2 [http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ebola-eng.php Public Health Agency of Canada Ebola virus- Pathogen Safety Data Sheets]<br />
<br><br />
3 [http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola/qa.htm CDC Questions and Answers about Ebola Hemorrhagic fever]<br />
<br><br />
4 [http://emedicine.medscape.com/article/216288-overview#aw2aab6b2b5 MedScape Ebola Virus] <br />
<br><br />
5 [http://www.mayoclinic.com/health/ebolavirus/DS00996/DSECTION=tests%2Dand%2Ddiagnosis Mayo Clinic Ebola Virus and Marburg Virus]<br />
<br><br />
6 [http://www.nlm.nih.gov/medlineplus/ency/article/001339.htm Medline Plus Ebola hemorrhagic fever]<br />
<br><br />
7 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061251/ Daisy W Leung, Kathleen C Prins, Christopher F Basler, and Gaya K Amarasinghe. Ebolavirus VP35 is a multifunctional virulence factor. US National Library of Medicine and National Institute of Health]<br />
<br><br />
8 [http://www.ncbi.nlm.nih.gov.ezproxy.lib.ou.edu/pubmed/15896665 Bray, Mike and Thomas W. Geisbert. Ebola virus: The role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever. US National Library of Medicine and National Institute of Health]<br />
<br><br />
9 [http://jvi.asm.org/content/77/18/9733 Sullivan, Nancy, Zhi-Yong Yang, and Gary J. Nabel. Ebola Virus Pathogenesis: Implications for Vaccines and Therapies. American Society for Microbiology]<br />
<br><br />
10 [http://www.ncbi.nlm.nih.gov/pubmed/20198110 JE, Lee and Saphire EO. Ebolavirus glycoprotein structure and mechanism of entry. US National Library of Medicine and National Institutes of Health]<br />
<br><br />
<br><br />
<br />
[[Image: OUA.png |thumb|400px|right| OU Microbiology in Arezzo, Italy]]<br />
<br />
Created by Bhumi Patel, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=EBOV&diff=91627EBOV2013-07-25T09:14:55Z<p>Danielle.L.Vinnedge-1: /* Symptoms */</p>
<hr />
<div>{{Curated}}<br />
<br />
[[Image: ebola4.jpeg |thumb|400px|right| The Ebola virus micrograph. From: http://www.thesundaytimes.co.uk/sto/culture/books/non_fiction/article1133688.ece]]<br />
==<b>Etiology</b>==<br />
===Taxonomy===<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Filoviridae]]<br />
| Genus = [[Ebolavirus]]<br />
| Species = [[Zaire ebolavirus]] |<br />
<br />
===Description===<br />
The Ebola virus was first detected in 1976 in the Democratic Republic of the Congo near the Ebola river; hence, the virus was named after the location of origin. (CDC). <br />
It is a negative-sense, non-segmented, enveloped RNA virus belonging to the Filoviridae family. There are five identified species of the virus, each named after the region they were localized. The Zaire, Sudan, Ivory Coast, and Bundibugyo affect humans; whereas, the Reston virus only causes disease in non-human primates. The natural reservoir of the virus remains unknown. However, non-human primates and fruit bats, of <i>Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata </i> species, are considered zoonotic reservoirs of the virus. The Reston virus was isolated from cynomolgous monkeys imported from the Philippines to the United States and Italy. <br />
Infection is characterized by septic shock, hemorrhagic fever, coagulation of cells, and tissue necrosis. Some individuals are able to recover, but most do not survive. It remains unknown as to why some survive and others die. It is classified as a level 4 disease by the CDC. [[#References|[1]]] [[#References|[2]]] [[#References|[3]]]<br />
<br />
==<b>Pathogenesis</b>==<br />
<br />
===Transmission===<br />
There are two types of exposures that contribute to acquiring the Ebola virus. The first, primary exposure, is due to travel in an ebola endemic area. The second mode of transmission is contact with bodily fluids of an infected host as well as utilizing unsterilized hospital equipment that came in contact with the virus. [[#References|[4]]]<br />
<br />
===Infectious dose and incubation===<br />
Upon invasion of host cells, the virus typically presents a 2-21 day incubation period. The infectious dose is very low; 1-10 aerosolized particles are sufficient to cause disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
As indicated by the chart provided by The World Health Organization, Ebola virus mainly affects regions in Africa. However, Reston strain did affect monkeys in the United States and Italy when they were imported from Italy. The Zaire virus outbreak seems to be the most predominant. The chart depicts outbreaks in Africa up until May 2012. <br />
<br />
<br />
<br />
[[Image: chart-1.jpeg |thumb|400px|center| Record of Ebola hemorrhagic outbreaks as of May 2012. From: http://www.who.int/mediacentre/factsheets/fs103/en/]]<br />
<br />
===Virulence Factors===<br />
EBOV viral strand contains seven genes encompassed in a 19 kb genome. Gene products produced are a glycoprotein (GP) virion envelope, nucleoprotein (NP), nonstructural proteins VP30 and VP35, matrix proteins VP24 and VP40, and a viral polymerase. VP35 and the GP are the major contributors to the onset of disease. [[#References|[9]]]<br />
<br />
====VP35====<br />
Previous studies demonstrate VP35 is protein virulence factor that serves as a cofactor for viral RNA polymerase complex, RNAi silencing suppressor and for viral assembly. In addition, VP35 promotes immune lapse by antagonizing antiviral signaling pathways and by denaturing the type I IFN system. Thus, the protein is able to replicate RNA and evade host cells. EBOV VP35 IID interferes with type I interferons (IFNs) and IFNα/β upon the engagement of PRRs and PAMPs, which in a normal immune response, produce the necessary type I IFNs. Transcription factors (IRF)3, IRF-7, and NKκ stimulate the IFNα/β to release IFNα and IFNβ. IFNα and IFNβ in turn stimulate antiviral activity genes like MHC class I and PKR. By activating these genes, we can reduce viral replication and in turn reduce the spread of infection. Inhibition of IFNα/β indirectly affects dendritic cell maturation because IFN production is reduced. [[#References|[7]]] [[#References|[9]]] <br />
<br />
The mechanism by which VP35 binds its RNA remains uncertain. However, structural studies of the protein reveal that it is comprised of two subdomains. The alpha subdomain is composed of a four helix bundle and the beta domain is composed of four antiparallel beta strands, alpha helix, and a polyproline helix. Furthermore, the VP35 contains two basic patches, one in the beta sheet subdomain and the other in the alpha helical subdomain. The beta sheet domain has Arg305, Arg12, and Lys309 that allow for further immune suppression. VP35 is also characterized by an “end cap” that is composed of hydrophobic Phe239 and Ile340; this hydrophobic area allows RNA to bind to VP35 IID; in turn, antagonize antiviral signaling pathways. The N-terminus of the protein is utilized to allow NP and VP40 binding, the formation of viral polymerase complex, PKR, and RNAi silencing suppression. Scientists believe that perhaps preventing the adherence of VP35, the ebola virus can be avoided in host cells. [[#References|[7]]] [[#References|[9]]]<br />
<br />
====GP====<br />
The glycoprotein (GP) envelope around EBOV allows the virus to adhere and fuse with host cells. Studies conducted in the past suggest that the GP holds a trimeric form with GP1 and GP2 (which are linked by a disulfide bond). A neutralizing antibody, KZ52, detected in a human EBOV survivor was utilized to crystalize the structure of the GP+antibody. GP1 attributes allow EBOV to attach to host cells. It is composed of a base, head, and glycan cap. The base forms a clamp that allows the stabilization of GP2 pre-fusion conformation. The GP2 subunit attributes allow EBOV to fuse with host cells. GP1 forms a chalice that is supported by GP2 whilst a glycan cap and mucin-like domain protect the receptor binding site. The neutralizing antibody detects proteins on the chalice base causing it to bind to GP1 via Van der Waals forces. EBOV then makes it’s entry into host cells via endocytosis. [[#References|[10]]]<br />
<br />
==<b>Clinical features</b>==<br />
===Symptoms===<br />
Ebola nfection is characterized by the onset of malaise, fever, myalgia, diarrhea, vomiting, and headaches. As the disease progresses, gastrointestinal bleeding, lymphopenia, neutrophilia, maculopapular rash, conjuctivitis, along with external bleeding may occur. Some patients are able to recover from the infection; however, it remains unknown as to why some recover and others die. <br />
Infected individuals are quarantined in a facility that entails the necessary safety measures authored by the CDC and WHO. Health care professionals dress in biohazard suits before coming in contact with a patient. If biohazard suits are not available, protective clothing, goggles, gloves, and mask should be worn.<br />
Survivors are typically left with a range of maladies that include fatigue, bulimia, hearing loss, tinnitus, arthralgias, orchitis, and suppurative parotitis. [[#References|[4]]] [[#References|[9]]]<br />
[[Image: ebolavictim.jpeg |thumb|400px|right| Ebola patient. <br /> From: http://news.bbc.co.uk/2/hi/africa/567974.stm]]<br />
<br />
===Mortality===<br />
Mortality rates are between 50-90%. It is possible to survive the Ebola virus; however, statistics suggest the EBOV is more fatal than the other species of the ebola virus. Epidemiological studies indicate that the Zaire species is predominant in infecting human hosts. [[#References|[9]]]<br />
<br />
==<b>Diagnosis</b>==<br />
Typically, clinical diagnosis can only be made after the first few days of symptoms because the early symptoms could have been caused by many other factors. <br />
Laboratory tests such as, enzyme-linked immunosorbent assay (ELISA), serum neturalization tests, antigen detection tests, virus isolation, and a reverse transcriptase polymerase chain reaction (RT-PCR) definitively allow the detection of the ebola virus in a patient. Immunohistochemistry testing and PCR can be conducted in patients that did not survive the disease. These tests are conducted under maximum biological containment conditions. [[#References|[1]]] [[#References|[2]]] [[#References|[3]]]<br />
<br />
==<b>Treatment</b>==<br />
Currently, vaccines and antivirals are not available to treat EBOV. Patients are provided supportive treatment that includes attention to: Replacement of fluids, electrolytes, constant monitoring of blood pressure and oxygen levels, nutrition and comfort. [[#References|[1]]]<br />
<br />
==<b>Prevention</b>==<br />
To reduce the risk of acquiring the Ebola virus, avoid travelling to endemic areas in Africa. In addition, avoid consuming bush meats that are sold on street markets. Wear gloves, protective clothing, and a mask when caring for an ill that may possibly be affect with ebola. Also avoid coming in contact with an infected corpse. Wash hands frequently when travelling; if no soap is available, rub hands with 60% alcohol. Take careful precautions before coming in contact with the fluids of non-human primates from Africa or the Philippines. [[#References|[1]]] [[#References|[5]]] [[#References|[6]]]<br />
[[Image: ebov.jpeg |thumb|400px|left| Depiction of health care professionals dressed in biohazard suits. From: http://foxfromzim.files.wordpress.com/2010/05/ebola.jpeg]]<br />
<br />
==<b>Host Immune Response</b>==<br />
The lack of infected human tissue prevents the pathologic study of EBOV; thus, studies conducted in cynomolgus monkeys only suggest the possible mechanisms of infection in humans. <br />
<br />
The GP gives EBOV access to host cells by allowing the transfer of the viral genome into macrophages. Infected cells may trigger antigen-specific immune responses to prevent viral replications; however, if immune responses fail, death occurs 1-2 weeks after infection. The present GP allows the virus to conveniently adhere to cell surface lectins in addition to a variety of other molecules. ZEBOV impairs the function of macrophages and dendritic cells in the immune response system. These antigen presenting cells are able to trigger inflammation and coagulation; however, they lack the ability to prevent RNA replication in the host cells.<br />
<br />
RNA binds to PRRs on the macrophage surface to trigger cytoplasmic signaling to cause the migration of vasoactive molecules like cytokines (TNF-alpha and IL-1beta), chemokines (MIP-1alpha), and nitric oxide. The release of these molecules causes additional macrophages and monocytes to migrate to the infected cell. Neutrophils are then released to aid the present macrophages. Lipid mediators trigger the inflammation response, which causes vasodilation, increased endothelial permeability, and expression of adhesion molecules to trap leukoctyes. This allows the virus to skillfully invade host immune cells to cause hypotension and septic shock. In addition, the binding of coagulation factors to cells excites intracellular signaling pathways by phosphorylating cytoplasmic TF tails; this hinders macrophage function. <br />
<br />
Infected dendritic cells fail to express costimulatory molecules, MHC, and thus, prevent differentiation of lymphocytes. ZEBOV does not invade lymphocytes; however, the presence of the virus does initiate cell apoptosis causing lymphopenia and thus, septic shock. Natural killer cells, CD4 and CD8 cells are the prominent cell types affected during the course of the disease. Typically, these cells play a critical role in preventing viral replication. [[#References|[8]]]<br />
<br />
==<b>References</b>==<br />
1 [http://www.who.int/mediacentre/factsheets/fs103/en/ WHO Fact Sheet on Ebola haemorrhagic fever]<br />
<br><br />
2 [http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ebola-eng.php Public Health Agency of Canada Ebola virus- Pathogen Safety Data Sheets]<br />
<br><br />
3 [http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola/qa.htm CDC Questions and Answers about Ebola Hemorrhagic fever]<br />
<br><br />
4 [http://emedicine.medscape.com/article/216288-overview#aw2aab6b2b5 MedScape Ebola Virus] <br />
<br><br />
5 [http://www.mayoclinic.com/health/ebolavirus/DS00996/DSECTION=tests%2Dand%2Ddiagnosis Mayo Clinic Ebola Virus and Marburg Virus]<br />
<br><br />
6 [http://www.nlm.nih.gov/medlineplus/ency/article/001339.htm Medline Plus Ebola hemorrhagic fever]<br />
<br><br />
7 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061251/ Daisy W Leung, Kathleen C Prins, Christopher F Basler, and Gaya K Amarasinghe. Ebolavirus VP35 is a multifunctional virulence factor. US National Library of Medicine and National Institute of Health]<br />
<br><br />
8 [http://www.ncbi.nlm.nih.gov.ezproxy.lib.ou.edu/pubmed/15896665 Bray, Mike and Thomas W. Geisbert. Ebola virus: The role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever. US National Library of Medicine and National Institute of Health]<br />
<br><br />
9 [http://jvi.asm.org/content/77/18/9733 Sullivan, Nancy, Zhi-Yong Yang, and Gary J. Nabel. Ebola Virus Pathogenesis: Implications for Vaccines and Therapies. American Society for Microbiology]<br />
<br><br />
10 [http://www.ncbi.nlm.nih.gov/pubmed/20198110 JE, Lee and Saphire EO. Ebolavirus glycoprotein structure and mechanism of entry. US National Library of Medicine and National Institutes of Health]<br />
<br><br />
<br><br />
<br />
[[Image: OUA.png |thumb|400px|right| OU Microbiology in Arezzo, Italy]]<br />
<br />
Created by Bhumi Patel, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=EBOV&diff=91622EBOV2013-07-25T09:11:12Z<p>Danielle.L.Vinnedge-1: /* Symptoms */</p>
<hr />
<div>{{Curated}}<br />
<br />
[[Image: ebola4.jpeg |thumb|400px|right| The Ebola virus micrograph. From: http://www.thesundaytimes.co.uk/sto/culture/books/non_fiction/article1133688.ece]]<br />
==<b>Etiology</b>==<br />
===Taxonomy===<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Filoviridae]]<br />
| Genus = [[Ebolavirus]]<br />
| Species = [[Zaire ebolavirus]] |<br />
<br />
===Description===<br />
The Ebola virus was first detected in 1976 in the Democratic Republic of the Congo near the Ebola river; hence, the virus was named after the location of origin. (CDC). <br />
It is a negative-sense, non-segmented, enveloped RNA virus belonging to the Filoviridae family. There are five identified species of the virus, each named after the region they were localized. The Zaire, Sudan, Ivory Coast, and Bundibugyo affect humans; whereas, the Reston virus only causes disease in non-human primates. The natural reservoir of the virus remains unknown. However, non-human primates and fruit bats, of <i>Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata </i> species, are considered zoonotic reservoirs of the virus. The Reston virus was isolated from cynomolgous monkeys imported from the Philippines to the United States and Italy. <br />
Infection is characterized by septic shock, hemorrhagic fever, coagulation of cells, and tissue necrosis. Some individuals are able to recover, but most do not survive. It remains unknown as to why some survive and others die. It is classified as a level 4 disease by the CDC. [[#References|[1]]] [[#References|[2]]] [[#References|[3]]]<br />
<br />
==<b>Pathogenesis</b>==<br />
<br />
===Transmission===<br />
There are two types of exposures that contribute to acquiring the Ebola virus. The first, primary exposure, is due to travel in an ebola endemic area. The second mode of transmission is contact with bodily fluids of an infected host as well as utilizing unsterilized hospital equipment that came in contact with the virus. [[#References|[4]]]<br />
<br />
===Infectious dose and incubation===<br />
Upon invasion of host cells, the virus typically presents a 2-21 day incubation period. The infectious dose is very low; 1-10 aerosolized particles are sufficient to cause disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
As indicated by the chart provided by The World Health Organization, Ebola virus mainly affects regions in Africa. However, Reston strain did affect monkeys in the United States and Italy when they were imported from Italy. The Zaire virus outbreak seems to be the most predominant. The chart depicts outbreaks in Africa up until May 2012. <br />
<br />
<br />
<br />
[[Image: chart-1.jpeg |thumb|400px|center| Record of Ebola hemorrhagic outbreaks as of May 2012. From: http://www.who.int/mediacentre/factsheets/fs103/en/]]<br />
<br />
===Virulence Factors===<br />
EBOV viral strand contains seven genes encompassed in a 19 kb genome. Gene products produced are a glycoprotein (GP) virion envelope, nucleoprotein (NP), nonstructural proteins VP30 and VP35, matrix proteins VP24 and VP40, and a viral polymerase. VP35 and the GP are the major contributors to the onset of disease. [[#References|[9]]]<br />
<br />
====VP35====<br />
Previous studies demonstrate VP35 is protein virulence factor that serves as a cofactor for viral RNA polymerase complex, RNAi silencing suppressor and for viral assembly. In addition, VP35 promotes immune lapse by antagonizing antiviral signaling pathways and by denaturing the type I IFN system. Thus, the protein is able to replicate RNA and evade host cells. EBOV VP35 IID interferes with type I interferons (IFNs) and IFNα/β upon the engagement of PRRs and PAMPs, which in a normal immune response, produce the necessary type I IFNs. Transcription factors (IRF)3, IRF-7, and NKκ stimulate the IFNα/β to release IFNα and IFNβ. IFNα and IFNβ in turn stimulate antiviral activity genes like MHC class I and PKR. By activating these genes, we can reduce viral replication and in turn reduce the spread of infection. Inhibition of IFNα/β indirectly affects dendritic cell maturation because IFN production is reduced. [[#References|[7]]] [[#References|[9]]] <br />
<br />
The mechanism by which VP35 binds its RNA remains uncertain. However, structural studies of the protein reveal that it is comprised of two subdomains. The alpha subdomain is composed of a four helix bundle and the beta domain is composed of four antiparallel beta strands, alpha helix, and a polyproline helix. Furthermore, the VP35 contains two basic patches, one in the beta sheet subdomain and the other in the alpha helical subdomain. The beta sheet domain has Arg305, Arg12, and Lys309 that allow for further immune suppression. VP35 is also characterized by an “end cap” that is composed of hydrophobic Phe239 and Ile340; this hydrophobic area allows RNA to bind to VP35 IID; in turn, antagonize antiviral signaling pathways. The N-terminus of the protein is utilized to allow NP and VP40 binding, the formation of viral polymerase complex, PKR, and RNAi silencing suppression. Scientists believe that perhaps preventing the adherence of VP35, the ebola virus can be avoided in host cells. [[#References|[7]]] [[#References|[9]]]<br />
<br />
====GP====<br />
The glycoprotein (GP) envelope around EBOV allows the virus to adhere and fuse with host cells. Studies conducted in the past suggest that the GP holds a trimeric form with GP1 and GP2 (which are linked by a disulfide bond). A neutralizing antibody, KZ52, detected in a human EBOV survivor was utilized to crystalize the structure of the GP+antibody. GP1 attributes allow EBOV to attach to host cells. It is composed of a base, head, and glycan cap. The base forms a clamp that allows the stabilization of GP2 pre-fusion conformation. The GP2 subunit attributes allow EBOV to fuse with host cells. GP1 forms a chalice that is supported by GP2 whilst a glycan cap and mucin-like domain protect the receptor binding site. The neutralizing antibody detects proteins on the chalice base causing it to bind to GP1 via Van der Waals forces. EBOV then makes it’s entry into host cells via endocytosis. [[#References|[10]]]<br />
<br />
==<b>Clinical features</b>==<br />
===Symptoms===<br />
Ebola nfection is characterized by the onset of malaise, fever, myalgia, diarrhea, vomiting, and headaches. As the disease progresses, gastrointestinal bleeding, lymphopenia, neutrophilia, maculopapular rash, conjuctivitis, along with external bleeding may occur. Some patients are able to recover from the infection; however, it remains unknown as to why some recover and others fail. <br />
Infected individuals are quarantined in a facility that entails the necessary safety measures authored by the CDC and WHO. Health care professionals dress in biohazard suits before coming in contact with a patient. If biohazard suits are not available, protective clothing, goggles, gloves, and mask should be worn.<br />
Survivors are typically left with a range of maladies that include fatigue, bulimia, hearing loss, tinnitus, arthralgias, orchitis, and suppurative parotitis. [[#References|[4]]] [[#References|[9]]]<br />
[[Image: ebolavictim.jpeg |thumb|400px|right| Ebola patient. <br /> From: http://news.bbc.co.uk/2/hi/africa/567974.stm]]<br />
<br />
===Mortality===<br />
Mortality rates are between 50-90%. It is possible to survive the Ebola virus; however, statistics suggest the EBOV is more fatal than the other species of the ebola virus. Epidemiological studies indicate that the Zaire species is predominant in infecting human hosts. [[#References|[9]]]<br />
<br />
==<b>Diagnosis</b>==<br />
Typically, clinical diagnosis can only be made after the first few days of symptoms because the early symptoms could have been caused by many other factors. <br />
Laboratory tests such as, enzyme-linked immunosorbent assay (ELISA), serum neturalization tests, antigen detection tests, virus isolation, and a reverse transcriptase polymerase chain reaction (RT-PCR) definitively allow the detection of the ebola virus in a patient. Immunohistochemistry testing and PCR can be conducted in patients that did not survive the disease. These tests are conducted under maximum biological containment conditions. [[#References|[1]]] [[#References|[2]]] [[#References|[3]]]<br />
<br />
==<b>Treatment</b>==<br />
Currently, vaccines and antivirals are not available to treat EBOV. Patients are provided supportive treatment that includes attention to: Replacement of fluids, electrolytes, constant monitoring of blood pressure and oxygen levels, nutrition and comfort. [[#References|[1]]]<br />
<br />
==<b>Prevention</b>==<br />
To reduce the risk of acquiring the Ebola virus, avoid travelling to endemic areas in Africa. In addition, avoid consuming bush meats that are sold on street markets. Wear gloves, protective clothing, and a mask when caring for an ill that may possibly be affect with ebola. Also avoid coming in contact with an infected corpse. Wash hands frequently when travelling; if no soap is available, rub hands with 60% alcohol. Take careful precautions before coming in contact with the fluids of non-human primates from Africa or the Philippines. [[#References|[1]]] [[#References|[5]]] [[#References|[6]]]<br />
[[Image: ebov.jpeg |thumb|400px|left| Depiction of health care professionals dressed in biohazard suits. From: http://foxfromzim.files.wordpress.com/2010/05/ebola.jpeg]]<br />
<br />
==<b>Host Immune Response</b>==<br />
The lack of infected human tissue prevents the pathologic study of EBOV; thus, studies conducted in cynomolgus monkeys only suggest the possible mechanisms of infection in humans. <br />
<br />
The GP gives EBOV access to host cells by allowing the transfer of the viral genome into macrophages. Infected cells may trigger antigen-specific immune responses to prevent viral replications; however, if immune responses fail, death occurs 1-2 weeks after infection. The present GP allows the virus to conveniently adhere to cell surface lectins in addition to a variety of other molecules. ZEBOV impairs the function of macrophages and dendritic cells in the immune response system. These antigen presenting cells are able to trigger inflammation and coagulation; however, they lack the ability to prevent RNA replication in the host cells.<br />
<br />
RNA binds to PRRs on the macrophage surface to trigger cytoplasmic signaling to cause the migration of vasoactive molecules like cytokines (TNF-alpha and IL-1beta), chemokines (MIP-1alpha), and nitric oxide. The release of these molecules causes additional macrophages and monocytes to migrate to the infected cell. Neutrophils are then released to aid the present macrophages. Lipid mediators trigger the inflammation response, which causes vasodilation, increased endothelial permeability, and expression of adhesion molecules to trap leukoctyes. This allows the virus to skillfully invade host immune cells to cause hypotension and septic shock. In addition, the binding of coagulation factors to cells excites intracellular signaling pathways by phosphorylating cytoplasmic TF tails; this hinders macrophage function. <br />
<br />
Infected dendritic cells fail to express costimulatory molecules, MHC, and thus, prevent differentiation of lymphocytes. ZEBOV does not invade lymphocytes; however, the presence of the virus does initiate cell apoptosis causing lymphopenia and thus, septic shock. Natural killer cells, CD4 and CD8 cells are the prominent cell types affected during the course of the disease. Typically, these cells play a critical role in preventing viral replication. [[#References|[8]]]<br />
<br />
==<b>References</b>==<br />
1 [http://www.who.int/mediacentre/factsheets/fs103/en/ WHO Fact Sheet on Ebola haemorrhagic fever]<br />
<br><br />
2 [http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ebola-eng.php Public Health Agency of Canada Ebola virus- Pathogen Safety Data Sheets]<br />
<br><br />
3 [http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola/qa.htm CDC Questions and Answers about Ebola Hemorrhagic fever]<br />
<br><br />
4 [http://emedicine.medscape.com/article/216288-overview#aw2aab6b2b5 MedScape Ebola Virus] <br />
<br><br />
5 [http://www.mayoclinic.com/health/ebolavirus/DS00996/DSECTION=tests%2Dand%2Ddiagnosis Mayo Clinic Ebola Virus and Marburg Virus]<br />
<br><br />
6 [http://www.nlm.nih.gov/medlineplus/ency/article/001339.htm Medline Plus Ebola hemorrhagic fever]<br />
<br><br />
7 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061251/ Daisy W Leung, Kathleen C Prins, Christopher F Basler, and Gaya K Amarasinghe. Ebolavirus VP35 is a multifunctional virulence factor. US National Library of Medicine and National Institute of Health]<br />
<br><br />
8 [http://www.ncbi.nlm.nih.gov.ezproxy.lib.ou.edu/pubmed/15896665 Bray, Mike and Thomas W. Geisbert. Ebola virus: The role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever. US National Library of Medicine and National Institute of Health]<br />
<br><br />
9 [http://jvi.asm.org/content/77/18/9733 Sullivan, Nancy, Zhi-Yong Yang, and Gary J. Nabel. Ebola Virus Pathogenesis: Implications for Vaccines and Therapies. American Society for Microbiology]<br />
<br><br />
10 [http://www.ncbi.nlm.nih.gov/pubmed/20198110 JE, Lee and Saphire EO. Ebolavirus glycoprotein structure and mechanism of entry. US National Library of Medicine and National Institutes of Health]<br />
<br><br />
<br><br />
<br />
[[Image: OUA.png |thumb|400px|right| OU Microbiology in Arezzo, Italy]]<br />
<br />
Created by Bhumi Patel, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=EBOV&diff=91610EBOV2013-07-25T08:57:26Z<p>Danielle.L.Vinnedge-1: /* Description */</p>
<hr />
<div>{{Curated}}<br />
<br />
[[Image: ebola4.jpeg |thumb|400px|right| The Ebola virus micrograph. From: http://www.thesundaytimes.co.uk/sto/culture/books/non_fiction/article1133688.ece]]<br />
==<b>Etiology</b>==<br />
===Taxonomy===<br />
| Order = [[Mononegavirales]]<br />
| Family = [[Filoviridae]]<br />
| Genus = [[Ebolavirus]]<br />
| Species = [[Zaire ebolavirus]] |<br />
<br />
===Description===<br />
The Ebola virus was first detected in 1976 in the Democratic Republic of the Congo near the Ebola river; hence, the virus was named after the location of origin. (CDC). <br />
It is a negative-strand, non-segmented, enveloped RNA virus belonging to the Filoviridae family. There are five identified species of the virus, each named after the region they were localized. The Zaire, Sudan, Ivory Coast, and Bundibugyo affect humans; whereas, the Reston virus only causes disease in non-human primates. The natural reservoir of the virus remains unknown. However, non-human primates and fruit bats, of <i>Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata </i> species, are considered zoonotic reservoirs of the virus. The Reston virus was isolated from cynomolgous monkeys imported from the Philippines to the United States and Italy. <br />
Infection is characterized by septic shock, hemorrhagic fever, coagulation of cells, and tissue necrosis. Some individuals are able to recover, but most do not survive. It remains unknown as to why some survive and others die. It is classified as a level 4 disease by the CDC. [[#References|[1]]] [[#References|[2]]] [[#References|[3]]]<br />
<br />
==<b>Pathogenesis</b>==<br />
<br />
===Transmission===<br />
There are two types of exposures that contribute to acquiring the Ebola virus. The first, primary exposure, is due to travel in an ebola endemic area. The second mode of transmission is contact with bodily fluids of an infected host as well as utilizing unsterilized hospital equipment that came in contact with the virus. [[#References|[4]]]<br />
<br />
===Infectious dose and incubation===<br />
Upon invasion of host cells, the virus typically presents a 2-21 day incubation period. The infectious dose is very low; 1-10 aerosolized particles are sufficient to cause disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
As indicated by the chart provided by The World Health Organization, Ebola virus mainly affects regions in Africa. However, Reston strain did affect monkeys in the United States and Italy when they were imported from Italy. The Zaire virus outbreak seems to be the most predominant. The chart depicts outbreaks in Africa up until May 2012. <br />
<br />
<br />
<br />
[[Image: chart-1.jpeg |thumb|400px|center| Record of Ebola hemorrhagic outbreaks as of May 2012. From: http://www.who.int/mediacentre/factsheets/fs103/en/]]<br />
<br />
===Virulence Factors===<br />
EBOV viral strand contains seven genes encompassed in a 19 kb genome. Gene products produced are a glycoprotein (GP) virion envelope, nucleoprotein (NP), nonstructural proteins VP30 and VP35, matrix proteins VP24 and VP40, and a viral polymerase. VP35 and the GP are the major contributors to the onset of disease. [[#References|[9]]]<br />
<br />
====VP35====<br />
Previous studies demonstrate VP35 is protein virulence factor that serves as a cofactor for viral RNA polymerase complex, RNAi silencing suppressor and for viral assembly. In addition, VP35 promotes immune lapse by antagonizing antiviral signaling pathways and by denaturing the type I IFN system. Thus, the protein is able to replicate RNA and evade host cells. EBOV VP35 IID interferes with type I interferons (IFNs) and IFNα/β upon the engagement of PRRs and PAMPs, which in a normal immune response, produce the necessary type I IFNs. Transcription factors (IRF)3, IRF-7, and NKκ stimulate the IFNα/β to release IFNα and IFNβ. IFNα and IFNβ in turn stimulate antiviral activity genes like MHC class I and PKR. By activating these genes, we can reduce viral replication and in turn reduce the spread of infection. Inhibition of IFNα/β indirectly affects dendritic cell maturation because IFN production is reduced. [[#References|[7]]] [[#References|[9]]] <br />
<br />
The mechanism by which VP35 binds its RNA remains uncertain. However, structural studies of the protein reveal that it is comprised of two subdomains. The alpha subdomain is composed of a four helix bundle and the beta domain is composed of four antiparallel beta strands, alpha helix, and a polyproline helix. Furthermore, the VP35 contains two basic patches, one in the beta sheet subdomain and the other in the alpha helical subdomain. The beta sheet domain has Arg305, Arg12, and Lys309 that allow for further immune suppression. VP35 is also characterized by an “end cap” that is composed of hydrophobic Phe239 and Ile340; this hydrophobic area allows RNA to bind to VP35 IID; in turn, antagonize antiviral signaling pathways. The N-terminus of the protein is utilized to allow NP and VP40 binding, the formation of viral polymerase complex, PKR, and RNAi silencing suppression. Scientists believe that perhaps preventing the adherence of VP35, the ebola virus can be avoided in host cells. [[#References|[7]]] [[#References|[9]]]<br />
<br />
====GP====<br />
The glycoprotein (GP) envelope around EBOV allows the virus to adhere and fuse with host cells. Studies conducted in the past suggest that the GP holds a trimeric form with GP1 and GP2 (which are linked by a disulfide bond). A neutralizing antibody, KZ52, detected in a human EBOV survivor was utilized to crystalize the structure of the GP+antibody. GP1 attributes allow EBOV to attach to host cells. It is composed of a base, head, and glycan cap. The base forms a clamp that allows the stabilization of GP2 pre-fusion conformation. The GP2 subunit attributes allow EBOV to fuse with host cells. GP1 forms a chalice that is supported by GP2 whilst a glycan cap and mucin-like domain protect the receptor binding site. The neutralizing antibody detects proteins on the chalice base causing it to bind to GP1 via Van der Waals forces. EBOV then makes it’s entry into host cells via endocytosis. [[#References|[10]]]<br />
<br />
==<b>Clinical features</b>==<br />
===Symptoms===<br />
Viral infection is characterized by the onset of malaise, fever, myalgia, diarrhea, vomiting, and headaches. As the disease progresses, gastrointestinal bleeding, lymphopenia, neutrophilia, maculopapular rash, conjuctivitis, along with external bleeding may occur. Some patients are able to recover from the infection; however, it remains unknown as to why some recover and others fail. <br />
Infected individuals are quarantined in a facility that entails the necessary safety measures authored by the CDC and WHO. Health care professionals dress in biohazard suits before coming in contact with a patient. If biohazard suits are not available, protective clothing, goggles, gloves, and mask should be worn.<br />
Survivors are typically left with a range of maladies that include fatigue, bulimia, hearing loss, tinnitus, arthralgias, orchitis, and suppurative parotitis. [[#References|[4]]] [[#References|[9]]]<br />
[[Image: ebolavictim.jpeg |thumb|400px|right| Ebola patient. <br /> From: http://news.bbc.co.uk/2/hi/africa/567974.stm]]<br />
<br />
===Mortality===<br />
Mortality rates are between 50-90%. It is possible to survive the Ebola virus; however, statistics suggest the EBOV is more fatal than the other species of the ebola virus. Epidemiological studies indicate that the Zaire species is predominant in infecting human hosts. [[#References|[9]]]<br />
<br />
==<b>Diagnosis</b>==<br />
Typically, clinical diagnosis can only be made after the first few days of symptoms because the early symptoms could have been caused by many other factors. <br />
Laboratory tests such as, enzyme-linked immunosorbent assay (ELISA), serum neturalization tests, antigen detection tests, virus isolation, and a reverse transcriptase polymerase chain reaction (RT-PCR) definitively allow the detection of the ebola virus in a patient. Immunohistochemistry testing and PCR can be conducted in patients that did not survive the disease. These tests are conducted under maximum biological containment conditions. [[#References|[1]]] [[#References|[2]]] [[#References|[3]]]<br />
<br />
==<b>Treatment</b>==<br />
Currently, vaccines and antivirals are not available to treat EBOV. Patients are provided supportive treatment that includes attention to: Replacement of fluids, electrolytes, constant monitoring of blood pressure and oxygen levels, nutrition and comfort. [[#References|[1]]]<br />
<br />
==<b>Prevention</b>==<br />
To reduce the risk of acquiring the Ebola virus, avoid travelling to endemic areas in Africa. In addition, avoid consuming bush meats that are sold on street markets. Wear gloves, protective clothing, and a mask when caring for an ill that may possibly be affect with ebola. Also avoid coming in contact with an infected corpse. Wash hands frequently when travelling; if no soap is available, rub hands with 60% alcohol. Take careful precautions before coming in contact with the fluids of non-human primates from Africa or the Philippines. [[#References|[1]]] [[#References|[5]]] [[#References|[6]]]<br />
[[Image: ebov.jpeg |thumb|400px|left| Depiction of health care professionals dressed in biohazard suits. From: http://foxfromzim.files.wordpress.com/2010/05/ebola.jpeg]]<br />
<br />
==<b>Host Immune Response</b>==<br />
The lack of infected human tissue prevents the pathologic study of EBOV; thus, studies conducted in cynomolgus monkeys only suggest the possible mechanisms of infection in humans. <br />
<br />
The GP gives EBOV access to host cells by allowing the transfer of the viral genome into macrophages. Infected cells may trigger antigen-specific immune responses to prevent viral replications; however, if immune responses fail, death occurs 1-2 weeks after infection. The present GP allows the virus to conveniently adhere to cell surface lectins in addition to a variety of other molecules. ZEBOV impairs the function of macrophages and dendritic cells in the immune response system. These antigen presenting cells are able to trigger inflammation and coagulation; however, they lack the ability to prevent RNA replication in the host cells.<br />
<br />
RNA binds to PRRs on the macrophage surface to trigger cytoplasmic signaling to cause the migration of vasoactive molecules like cytokines (TNF-alpha and IL-1beta), chemokines (MIP-1alpha), and nitric oxide. The release of these molecules causes additional macrophages and monocytes to migrate to the infected cell. Neutrophils are then released to aid the present macrophages. Lipid mediators trigger the inflammation response, which causes vasodilation, increased endothelial permeability, and expression of adhesion molecules to trap leukoctyes. This allows the virus to skillfully invade host immune cells to cause hypotension and septic shock. In addition, the binding of coagulation factors to cells excites intracellular signaling pathways by phosphorylating cytoplasmic TF tails; this hinders macrophage function. <br />
<br />
Infected dendritic cells fail to express costimulatory molecules, MHC, and thus, prevent differentiation of lymphocytes. ZEBOV does not invade lymphocytes; however, the presence of the virus does initiate cell apoptosis causing lymphopenia and thus, septic shock. Natural killer cells, CD4 and CD8 cells are the prominent cell types affected during the course of the disease. Typically, these cells play a critical role in preventing viral replication. [[#References|[8]]]<br />
<br />
==<b>References</b>==<br />
1 [http://www.who.int/mediacentre/factsheets/fs103/en/ WHO Fact Sheet on Ebola haemorrhagic fever]<br />
<br><br />
2 [http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/ebola-eng.php Public Health Agency of Canada Ebola virus- Pathogen Safety Data Sheets]<br />
<br><br />
3 [http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola/qa.htm CDC Questions and Answers about Ebola Hemorrhagic fever]<br />
<br><br />
4 [http://emedicine.medscape.com/article/216288-overview#aw2aab6b2b5 MedScape Ebola Virus] <br />
<br><br />
5 [http://www.mayoclinic.com/health/ebolavirus/DS00996/DSECTION=tests%2Dand%2Ddiagnosis Mayo Clinic Ebola Virus and Marburg Virus]<br />
<br><br />
6 [http://www.nlm.nih.gov/medlineplus/ency/article/001339.htm Medline Plus Ebola hemorrhagic fever]<br />
<br><br />
7 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3061251/ Daisy W Leung, Kathleen C Prins, Christopher F Basler, and Gaya K Amarasinghe. Ebolavirus VP35 is a multifunctional virulence factor. US National Library of Medicine and National Institute of Health]<br />
<br><br />
8 [http://www.ncbi.nlm.nih.gov.ezproxy.lib.ou.edu/pubmed/15896665 Bray, Mike and Thomas W. Geisbert. Ebola virus: The role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever. US National Library of Medicine and National Institute of Health]<br />
<br><br />
9 [http://jvi.asm.org/content/77/18/9733 Sullivan, Nancy, Zhi-Yong Yang, and Gary J. Nabel. Ebola Virus Pathogenesis: Implications for Vaccines and Therapies. American Society for Microbiology]<br />
<br><br />
10 [http://www.ncbi.nlm.nih.gov/pubmed/20198110 JE, Lee and Saphire EO. Ebolavirus glycoprotein structure and mechanism of entry. US National Library of Medicine and National Institutes of Health]<br />
<br><br />
<br><br />
<br />
[[Image: OUA.png |thumb|400px|right| OU Microbiology in Arezzo, Italy]]<br />
<br />
Created by Bhumi Patel, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90964Anthrax2013-07-23T12:51:09Z<p>Danielle.L.Vinnedge-1: /* Transmission */</p>
<hr />
<div>{{Curated}}<br />
[[Image:OUA.png|thumb|240px|center|Microbiology in Italy[http://cas.ou.edu/study-abroad/]]]<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the Bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals and humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
[[Image:anthraxspores.jpeg|frame|right|''Anthrax spores in the lung'' [http://microculture.tumblr.com/post/6479280426/scientistintraining-bacillus-anthracis-spores.]]]<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogenesis begins by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate the vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxin begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax, and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead infected caribou. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:anthraxtoxins.jpeg|thumb|400px|right|<i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor(EF), and toxic factor(LeTx). [http://www.sciencedirect.com/science/article/pii/S0006349510004790.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function and causes cell apoptosis. Lethal factor also disrupts downstream signaling, which is important in normal cell functioning. Edema factor is a potent adenyl cyclase and works additively with lethal factor. EF causes increase cAMP production in infected cells and also has immunosuppressive effects like LF. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Lethal and Edema factors both have immunosuppressive effects that make anthrax such a lethal disease. LF and EF inhibit proliferation of CD4 T cells, neutrophile phagocytosis, cytokine production, IL-2 production, and cause macrophage lysis. Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[8]]] [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and 11 confirmed or suspected cases of cutaneous anthrax. Five people died. [[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90960Anthrax2013-07-23T12:48:49Z<p>Danielle.L.Vinnedge-1: /* Pathogenesis */</p>
<hr />
<div>{{Curated}}<br />
[[Image:OUA.png|thumb|240px|center|Microbiology in Italy[http://cas.ou.edu/study-abroad/]]]<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the Bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals and humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
[[Image:anthraxspores.jpeg|frame|right|''Anthrax spores in the lung'' [http://microculture.tumblr.com/post/6479280426/scientistintraining-bacillus-anthracis-spores.]]]<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogenesis begins by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate the vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxin begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax, and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead infected caribou. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:anthraxtoxins.jpeg|thumb|400px|right|<i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor(EF), and toxic factor(LeTx). [http://www.sciencedirect.com/science/article/pii/S0006349510004790.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function and causes cell apoptosis. Lethal factor also disrupts downstream signaling, which is important in normal cell functioning. Edema factor is a potent adenyl cyclase and works additively with lethal factor. EF causes increase cAMP production in infected cells and also has immunosuppressive effects like LF. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Lethal and Edema factors both have immunosuppressive effects that make anthrax such a lethal disease. LF and EF inhibit proliferation of CD4 T cells, neutrophile phagocytosis, cytokine production, IL-2 production, and cause macrophage lysis. Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[8]]] [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and 11 confirmed or suspected cases of cutaneous anthrax. Five people died. [[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90953Anthrax2013-07-23T12:37:47Z<p>Danielle.L.Vinnedge-1: /* History */</p>
<hr />
<div>{{Curated}}<br />
[[Image:OUA.png|thumb|240px|center|Microbiology in Italy[http://cas.ou.edu/study-abroad/]]]<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the Bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals and humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
[[Image:anthraxspores.jpeg|frame|right|''Anthrax spores in the lung'' [http://microculture.tumblr.com/post/6479280426/scientistintraining-bacillus-anthracis-spores.]]]<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:anthraxtoxins.jpeg|thumb|400px|right|<i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor(EF), and toxic factor(LeTx). [http://www.sciencedirect.com/science/article/pii/S0006349510004790.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function and causes cell apoptosis. Lethal factor also disrupts downstream signaling which is important in normal cell functioning. Edema factor is a potent adenyl cyclase and works additively with lethal factor. EF causes increase cAMP production in infected cells and also has immunosuppressive effects like LeTx. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Lethal and Edema factors both have immunosuppressive effects that make anthrax such a lethal disease. LF and EF inhibit proliferation of CD4 T cells, neutrophile phagocytosis, cytokine production, IL-2 production, and cause macrophage lysis. Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[8]]] [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and 11 confirmed or suspected cases of cutaneous anthrax. Five people died. [[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=File:Anthraxspores.jpeg&diff=90835File:Anthraxspores.jpeg2013-07-23T09:55:10Z<p>Danielle.L.Vinnedge-1: </p>
<hr />
<div></div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90833Anthrax2013-07-23T09:54:29Z<p>Danielle.L.Vinnedge-1: </p>
<hr />
<div>{{Curated}}<br />
[[Image:OUA.png|thumb|240px|center|Microbiology in Italy[http://cas.ou.edu/study-abroad/]]]<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
[[Image:anthraxspores.jpeg|frame|right|''Anthrax spores in the lung'' [http://microculture.tumblr.com/post/6479280426/scientistintraining-bacillus-anthracis-spores.]]]<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:anthraxtoxins.jpeg|thumb|400px|right|<i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor(EF), and toxic factor(LeTx). [http://www.sciencedirect.com/science/article/pii/S0006349510004790.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function and causes cell apoptosis. Lethal factor also disrupts downstream signaling which is important in normal cell functioning. Edema factor is a potent adenyl cyclase and works additively with lethal factor. EF causes increase cAMP production in infected cells and also has immunosuppressive effects like LeTx. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Lethal and Edema factors both have immunosuppressive effects that make anthrax such a lethal disease. LF and EF inhibit proliferation of CD4 T cells, neutrophile phagocytosis, cytokine production, IL-2 production, and cause macrophage lysis. Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[8]]] [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and 11 confirmed or suspected cases of cutaneous anthrax. Five people died. [[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90822Anthrax2013-07-23T09:48:38Z<p>Danielle.L.Vinnedge-1: </p>
<hr />
<div>{{Curated}}<br />
[[Image:OUA.png|thumb|240px|center|Microbiology in Italy[http://cas.ou.edu/study-abroad/]]]<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:anthraxtoxins.jpeg|thumb|400px|right|<i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor(EF), and toxic factor(LeTx). [http://www.sciencedirect.com/science/article/pii/S0006349510004790.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function and causes cell apoptosis. Lethal factor also disrupts downstream signaling which is important in normal cell functioning. Edema factor is a potent adenyl cyclase and works additively with lethal factor. EF causes increase cAMP production in infected cells and also has immunosuppressive effects like LeTx. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Lethal and Edema factors both have immunosuppressive effects that make anthrax such a lethal disease. LF and EF inhibit proliferation of CD4 T cells, neutrophile phagocytosis, cytokine production, IL-2 production, and cause macrophage lysis. Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[8]]] [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and 11 confirmed or suspected cases of cutaneous anthrax. Five people died. [[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90780Anthrax2013-07-23T09:08:25Z<p>Danielle.L.Vinnedge-1: /* Bioterrorism */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:anthraxtoxins.jpeg|thumb|400px|right|<i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor(EF), and toxic factor(LeTx). [http://www.sciencedirect.com/science/article/pii/S0006349510004790.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function and causes cell apoptosis. Lethal factor also disrupts downstream signaling which is important in normal cell functioning. Edema factor is a potent adenyl cyclase and works additively with lethal factor. EF causes increase cAMP production in infected cells and also has immunosuppressive effects like LeTx. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Lethal and Edema factors both have immunosuppressive effects that make anthrax such a lethal disease. LF and EF inhibit proliferation of CD4 T cells, neutrophile phagocytosis, cytokine production, IL-2 production, and cause macrophage lysis. Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[8]]] [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and 11 confirmed or suspected cases of cutaneous anthrax. Five people died. [[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90779Anthrax2013-07-23T09:02:31Z<p>Danielle.L.Vinnedge-1: /* Host Immune Response */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:anthraxtoxins.jpeg|thumb|400px|right|<i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor(EF), and toxic factor(LeTx). [http://www.sciencedirect.com/science/article/pii/S0006349510004790.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function and causes cell apoptosis. Lethal factor also disrupts downstream signaling which is important in normal cell functioning. Edema factor is a potent adenyl cyclase and works additively with lethal factor. EF causes increase cAMP production in infected cells and also has immunosuppressive effects like LeTx. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Lethal and Edema factors both have immunosuppressive effects that make anthrax such a lethal disease. LF and EF inhibit proliferation of CD4 T cells, neutrophile phagocytosis, cytokine production, IL-2 production, and cause macrophage lysis. Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[8]]] [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90777Anthrax2013-07-23T09:01:25Z<p>Danielle.L.Vinnedge-1: /* Host Immune Response */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:anthraxtoxins.jpeg|thumb|400px|right|<i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor(EF), and toxic factor(LeTx). [http://www.sciencedirect.com/science/article/pii/S0006349510004790.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function and causes cell apoptosis. Lethal factor also disrupts downstream signaling which is important in normal cell functioning. Edema factor is a potent adenyl cyclase and works additively with lethal factor. EF causes increase cAMP production in infected cells and also has immunosuppressive effects like LeTx. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Lethal and Edema factors both have immunosuppressive effects that make anthrax such a lethal disease. LF and EF inhibit proliferation of CD4 T cells, neutrophile phagocytosis, cytokine production, IL-2 production, and cause macrophage lysis. Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=File:Anthraxtoxins.jpeg&diff=90762File:Anthraxtoxins.jpeg2013-07-23T08:30:02Z<p>Danielle.L.Vinnedge-1: </p>
<hr />
<div></div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90761Anthrax2013-07-23T08:29:36Z<p>Danielle.L.Vinnedge-1: /* Virulence factors */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:anthraxtoxins.jpeg|thumb|400px|right|<i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor(EF), and toxic factor(LeTx). [http://www.sciencedirect.com/science/article/pii/S0006349510004790.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function and causes cell apoptosis. Lethal factor also disrupts downstream signaling which is important in normal cell functioning. Edema factor is a potent adenyl cyclase and works additively with lethal factor. EF causes increase cAMP production in infected cells and also has immunosuppressive effects like LeTx. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90759Anthrax2013-07-23T08:25:06Z<p>Danielle.L.Vinnedge-1: /* Virulence factors */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:Mechanism of Anthrax.gif|thumb|400px|right|Figure 3. <i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor(EF), and toxic factor(LeTx). [http://www.rndsystems.com/cb_detail_objectname_FA03_Bacillus.aspx Image from R&D systems.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function and causes cell apoptosis. Lethal factor also disrupts downstream signaling which is important in normal cell functioning. Edema factor is a potent adenyl cyclase and works additively with lethal factor. EF causes increase cAMP production in infected cells and also has immunosuppressive effects like LeTx. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90753Anthrax2013-07-23T08:20:54Z<p>Danielle.L.Vinnedge-1: /* Host Immune Response */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:Mechanism of Anthrax.gif|thumb|400px|right|Figure 3. <i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor, and toxic factor. [http://www.rndsystems.com/cb_detail_objectname_FA03_Bacillus.aspx Image from R&D systems.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function and causes cell apoptosis. Lethal factor also disrupts downstream signaling which is important in normal cell functioning. Edema factor is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90750Anthrax2013-07-23T08:19:29Z<p>Danielle.L.Vinnedge-1: /* Virulence factors */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:Mechanism of Anthrax.gif|thumb|400px|right|Figure 3. <i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor, and toxic factor. [http://www.rndsystems.com/cb_detail_objectname_FA03_Bacillus.aspx Image from R&D systems.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function and causes cell apoptosis. Lethal factor also disrupts downstream signaling which is important in normal cell functioning. Edema factor is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90743Anthrax2013-07-23T08:06:50Z<p>Danielle.L.Vinnedge-1: /* Clinical features */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:Mechanism of Anthrax.gif|thumb|400px|right|Figure 3. <i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor, and toxic factor. [http://www.rndsystems.com/cb_detail_objectname_FA03_Bacillus.aspx Image from R&D systems.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomiting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90660Anthrax2013-07-22T20:47:08Z<p>Danielle.L.Vinnedge-1: /* Virulence factors */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:Mechanism of Anthrax.gif|thumb|400px|right|Figure 3. <i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor, and toxic factor. [http://www.rndsystems.com/cb_detail_objectname_FA03_Bacillus.aspx Image from R&D systems.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90652Anthrax2013-07-22T20:38:54Z<p>Danielle.L.Vinnedge-1: /* Pathogenesis */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum, in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:Mechanism of Anthrax.gif|thumb|300px|right|Figure 3. <i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor, and toxic factor. [http://www.rndsystems.com/cb_detail_objectname_FA03_Bacillus.aspx Image from R&D systems.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90651Anthrax2013-07-22T20:37:55Z<p>Danielle.L.Vinnedge-1: /* Virulence factors */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:Mechanism of Anthrax.gif|thumb|300px|right|Figure 3. <i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor, and toxic factor. [http://www.rndsystems.com/cb_detail_objectname_FA03_Bacillus.aspx Image from R&D systems.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90650Anthrax2013-07-22T20:36:56Z<p>Danielle.L.Vinnedge-1: /* Description */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen causes black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:Mechanism of Anthrax.gif|thumb|300px|right|Figure 3. <i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor, and toxic factor. [http://www.rndsystems.com/cb_detail_objectname_FA03_Bacillus.aspx Image from R&D systems.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90636Anthrax2013-07-22T20:26:23Z<p>Danielle.L.Vinnedge-1: /* Virulence factors */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
[[Image:Mechanism of Anthrax.gif|thumb|300px|right|Figure 3. <i>B. anthracis</i> secretes three proteins to form the Anthrax toxin: protective antigen, edema factor, and toxic factor. [http://www.rndsystems.com/cb_detail_objectname_FA03_Bacillus.aspx Image from R&D systems.]]]<br />
<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90605Anthrax2013-07-22T20:03:00Z<p>Danielle.L.Vinnedge-1: /* Virulence factors */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis</I> has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90604Anthrax2013-07-22T20:02:10Z<p>Danielle.L.Vinnedge-1: /* Clinical features */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90602Anthrax2013-07-22T20:01:43Z<p>Danielle.L.Vinnedge-1: /* Clinical features */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<b>Inhalation</b><br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90599Anthrax2013-07-22T20:01:11Z<p>Danielle.L.Vinnedge-1: /* Clinical features */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<b>Cutaneous</b><br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
<b>Gastrointestinal</b><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
<b>Inhalation</b><br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90598Anthrax2013-07-22T19:59:51Z<p>Danielle.L.Vinnedge-1: /* Clinical features */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
<br>Cutaneous</br><br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
<br>Gastrointestinal</br><br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
<br>Inhalation</br><br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90595Anthrax2013-07-22T19:56:50Z<p>Danielle.L.Vinnedge-1: /* Clinical features */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90594Anthrax2013-07-22T19:55:24Z<p>Danielle.L.Vinnedge-1: /* Diagnosis */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90593Anthrax2013-07-22T19:54:29Z<p>Danielle.L.Vinnedge-1: /* Diagnosis */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br><br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90592Anthrax2013-07-22T19:53:21Z<p>Danielle.L.Vinnedge-1: </p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History==<br />
<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
==Bioterrorism==<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90591Anthrax2013-07-22T19:51:44Z<p>Danielle.L.Vinnedge-1: /* Bioterrorism */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
===Bioterrorism===<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90586Anthrax2013-07-22T19:46:34Z<p>Danielle.L.Vinnedge-1: /* Bioterrorism */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
===Bioterrorism===<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. [[#References|[2]]]<br />
During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.[[#References|[13]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90583Anthrax2013-07-22T19:39:40Z<p>Danielle.L.Vinnedge-1: /* Bioterrorism */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
===Bioterrorism===<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sought to make anthrax a weapon. (2) During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail. During this outbreak there were 11 confirmed cases of inhalation anthrax and confirmed or suspected cases of cutaneous anthrax.(13)<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90578Anthrax2013-07-22T19:30:19Z<p>Danielle.L.Vinnedge-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
===Bioterrorism===<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sough to make anthrax a weapon (2). During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail which resulted in<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90575Anthrax2013-07-22T19:29:19Z<p>Danielle.L.Vinnedge-1: /* Bioterrorism */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
===Bioterrorism===<br />
[[Image:anthraxbioterrorism.jpeg|frame|right|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sough to make anthrax a weapon (2). During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail which resulted in<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
14. http://www.sciencedirect.com.ezproxy.lib.ou.edu/science/article/pii/S0736467903000799<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90397Anthrax2013-07-22T15:59:02Z<p>Danielle.L.Vinnedge-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
===Bioterrorism===<br />
[[Image:anthraxbioterrorism.jpeg|frame|left|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sough to make anthrax a weapon (2). During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail which resulted in<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br><br />
14. http://www.sciencedirect.com.ezproxy.lib.ou.edu/science/article/pii/S0736467903000799<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90391Anthrax2013-07-22T15:15:58Z<p>Danielle.L.Vinnedge-1: /* Bioterrorism */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
===Bioterrorism===<br />
[[Image:anthraxbioterrorism.jpeg|frame|left|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
Today, most people associate anthrax with biological warfare instead of a disease acquired from infected domesticated animals. A major effort during World War II sough to make anthrax a weapon (2). During the fall of 2001, an anthrax outbreak occurred due to spore-containing mail which resulted in<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90365Anthrax2013-07-22T13:51:42Z<p>Danielle.L.Vinnedge-1: /* Discovery */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. [[#References|[13]]] <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.[[#References|[13]]]<br />
<br />
===Bioterrorism===<br />
[[#References|[2]]]<br />
[[Image:anthraxbioterrorism.jpeg|frame|left|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90364Anthrax2013-07-22T13:51:08Z<p>Danielle.L.Vinnedge-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.<br />
<br />
===Bioterrorism===<br />
[[#References|[2]]]<br />
[[Image:anthraxbioterrorism.jpeg|frame|left|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12.http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br><br />
13. http://www.ncbi.nlm.nih.gov/pubmed/12745053<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90362Anthrax2013-07-22T13:49:48Z<p>Danielle.L.Vinnedge-1: /* Discovery */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
Anthrax has been described since antiquity. Stories of anthrax plague appear in the bible and the ancient Greeks described the cutaneous infection as coal-like (<i>anthrakites</i>) in appearance. The Roman poet Virgil also discussed the disease in domestic animals. Anthrax continued to affect domestic animals in humans in the Middle Ages and was referred as "woolsorters' disease" in England due to mill workers contracting the disease from sheep wool. Anthrax cases in the 20th century decreased significantly due to vaccination of animals. <br />
<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]These experiments served as the prototype for Koch's postulates.<br />
<br />
===Bioterrorism===<br />
[[#References|[2]]]<br />
[[Image:anthraxbioterrorism.jpeg|frame|left|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90338Anthrax2013-07-22T13:29:48Z<p>Danielle.L.Vinnedge-1: /* Discovery */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease. [[#References|[12]]]<br />
<br />
===Bioterrorism===<br />
[[#References|[2]]]<br />
[[Image:anthraxbioterrorism.jpeg|frame|left|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90337Anthrax2013-07-22T13:29:12Z<p>Danielle.L.Vinnedge-1: /* Discovery */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease. Koch did this by removing anthrax bacilli from the spleens of mice that had died from the disease and injected the blood into healthy mice, which killed the previously healthy mice. This illustrated the disease could be passed by blood from infected animals. He also created pure cultures of the bacilli and showed that this also caused disease.<br />
<br />
===Bioterrorism===<br />
[[#References|[2]]]<br />
[[Image:anthraxbioterrorism.jpeg|frame|left|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90322Anthrax2013-07-22T13:02:57Z<p>Danielle.L.Vinnedge-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease.<br />
<br />
===Bioterrorism===<br />
[[#References|[2]]]<br />
[[Image:anthraxbioterrorism.jpeg|frame|left|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
12. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1905/koch-bio.html<br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90321Anthrax2013-07-22T13:01:46Z<p>Danielle.L.Vinnedge-1: /* Discovery */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
The discovery of <i>Bacillus anthracis</i> is credited to Pollender, Rayer and Davaine. Robert Koch proved that the anthrax bacillus caused the disease.<br />
<br />
===Bioterrorism===<br />
[[#References|[2]]]<br />
[[Image:anthraxbioterrorism.jpeg|frame|left|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90309Anthrax2013-07-22T12:47:02Z<p>Danielle.L.Vinnedge-1: /* Treatment */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
===Bioterrorism===<br />
[[#References|[2]]]<br />
[[Image:anthraxbioterrorism.jpeg|frame|left|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic. [[#References|[6]]]<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1https://microbewiki.kenyon.edu/index.php?title=Anthrax&diff=90308Anthrax2013-07-22T12:46:05Z<p>Danielle.L.Vinnedge-1: /* Diagnosis */</p>
<hr />
<div>{{Curated}}<br />
[[Image:anthraxstructure.jpeg|frame|right|''Bacillus anthracis'' [http://m.kienthuc.net.vn/khoa-hoc/201210/The-gioi-vi-khuan-quot-lung-linh-quot-duoi-kinh-hien-vi-880630/.]]]<br />
<br />
==History and Culture==<br />
===Discovery===<br />
===Bioterrorism===<br />
[[#References|[2]]]<br />
[[Image:anthraxbioterrorism.jpeg|frame|left|''Anthrax bioterrorism'' [http://news.stanford.edu/news/2005/april20/med-anthrax-042005.html.]]]<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
Domain: Bacteria<br />
<br><br />
Phylum: Firmicutes<br />
<br><br />
Class: Bacilli<br />
<br><br />
Order: Bacillales<br />
<br><br />
Family: Bacillaceae<br />
<br><br />
Genus: <i>Bacillus</i><br />
<br><br />
Species: <i>anthracis</i><br />
<br />
===Description===<br />
<i>Bacillus anthracis </i> is a Gram-positive facultative aerobic spore-forming bacterium found in the soil. <i>B. anthracis</i> derived its name from the Greek word for coal because this pathogen can cause black lesions on the victim's skin. The bacterium is non-motile and non-hemolytic on blood agar. <i>B. anthracis</i> is found mostly in spore-form in the environment, but when it has infected a host it will germinate and replicate in essentially all body tissues.[[#References|[3]]] When <i> anthracis</i> is in the spore form, it is resistant to most adverse environments and can survive for many decades. [[#References|[2]]]<br />
<br />
==Pathogenesis==<br />
<i>B. anthracis</i> pathogensis occurs first by the spores entering a skin abrasion, lungs, or intestines. There, the spores are ingested by macrophages and brough to lymph nodes. The bacteria germinate in the lymph nodes or mediastinum in the case of inhalation anthrax. Local production of toxins cause edema and necrosis then bacterimia and toxemia. Seeding of other organ systems occur and the infection spreads. [[#References|[5]]] <br />
===Transmission===<br />
The most common way a human can contract anthrax is being in contact with infected animal products.[[#References|[4]]] Herbivore grazing animals can commonly contract anthrax because <i> anthracis </i> lives in the soil. A person may get anthrax by inhaling the spores from animal products, such as wool, have an open abrasion on the skin be exposed to the spores, or eating undercooked meat from an animal that was infected. More than 90% of anthrax cases are the cutaneous exposures. Anthrax cannot be spread person-to-person. [[#References|[2]]]<br />
<br />
===Infectious dose, incubation, and colonization===<br />
The infectious dose of <i>B. anthracis</i> is not entirely clear. Some suggest 100 spores will cause infection while some analysis have shown as few as 1-3 spores will cause infection. For inhalation anthrax, the infectious dose can be 8-50,000 spores. <br />
<br><br />
<br />
The incubation time also depends on what time of anthrax is contracted. For inhalation anthrax, the incubation period is 2-5 days. Cutaneous anthrax will start to manifest symptoms within 2-3 days, with some cases being as short as 12 hours. Gastrointestinal anthrax is much more rare and the incubation time isn't known. <br />
<br><br />
<br />
If infected with inhalation anthrax, the spores are deposited in the alveolar spaces and then transported to mediastinal lymph nodes. After the spores germinate, and vegetative bacteria will spread to the blood and lymph and cause septecimia. For ingested and cutaneous anthrax, the spores enter through a break in the skin or a break in the mucosa of the intestines. They are engulfed by macrophages, where they germinate and then extracellular replication will occur. During this replication phase, the capsule and toxins begin to be secreted which will cause symptoms and the disease. [[#References|[2]]]<br />
<br />
===Epidemiology===<br />
Most inhalation anthrax cases have occured in the factory setting when workers are exposed to contaminated animal products, like wool. Inhalation anthrax is very rare in the United States due to vast vaccination of domesticated livestock. Gastrointestinal anthrax is the rarest form of anthrax and in the United States there has only been two reported cases. In 2010, the Philippines had a 400 person outbreak of gastrointestinal anthrax from eating meat from a dead carabo. The largest epidemic to date happened in Zimbabwae between 1979-1985 when 10,000 people contracted cutaneous anthrax. [[#References|[2]]]<br />
<br />
===Virulence factors===<br />
<i>Bacillus anthracis has two components to its virulence. The toxin it secrets as well as its capsule. The capsule is composed of D-glutamyl polypeptide. Plasmid pXO2 is involved in the formation of the capsule. The capsule prevents host phagocytosis when <i>B. anthracis</i> is in its vegetative form. Plasmid pXO1 is responsible for the toxin released. The toxin has three proteins: the edema factor, lethal factor, and protective antigen. The protective antigen is a binding domain that allows the toxins (edema and lethal factors) to enter host cells. Lethal toxin causes immunosuppressive effects as well as damage endothelial cell function. Edema factor, is a potent adenyl cyclase and works additively with lethal factor. Both plasmids for capsule formation and toxin secretion have to be present in order for <i>B. anthracis</i> to be virulent. [[#References|[2]]] [[#References|[7]]] [[#References|[8]]]<br />
<br />
==Clinical features==<br />
[[Image:anthraxtypes.jpeg|frame|right|''The three types of anthrax infection[http://www.anthrax.osd.mil/disease/infection.asp.]]]<br />
===Cutaneous===<br />
<br />
<br />
The first sign of a cutaneous anthrax infection is a papule that eventually forms an ulcer with a black center. These lesions are painless. Fever rarely occurs with cutaneous anthrax infections. [[#References|[6]]]<br />
<br />
===Inhalation===<br />
<br />
<br />
<br />
If infected with inhalation anthrax, the first symptoms are flu-like and include fever, malaise, cough, and fatigue. After 48 hours, fever, tachypnoea, cyanosis, tachycardia, moist rales, and evidence of pleural effusion may be present. The pulse will be rapid and faint, the patient will become disoriented, and coma and death will soon follow. In half of the patients, meningitis will occur. Meningitis can occur from all three forms of anthrax and the mortality rate after contracting meningitis is near 100%.[[#References|[6]]]<br />
<br />
===Gastrointestinal===<br />
Gastrointenstinal anthrax presents itself initially with nausea, vomitting and anorexia, and fever. If left untreated, gastrointestinal anthrax will cause severe abdominal pain, haematemesis, bloody diarrhea, septicemia, and death. The initial symptoms our non-specific and can make it difficult to diagnose, resulting in a high mortality rate. [[#References|[6]]]<br />
<br />
==Diagnosis==<br />
<br />
To demonstrate that a patient is infected with <i>B. anthracis</i>, a methylene blue stain can be done as well as a blood agar culture. Anthrax will appear as a large Gram-positive rod after staining. A serologic diagnosis of anthrax can be made using a test specific for the protective antigen (PA) component of the toxin. [[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Cutaneous</b><br />
<br><br />
Cutaneous anthrax must first be distringuished from plague. The patient also has an appropriate history of being around exposed animals. A specimen may be obtained from the ulcer and cultured on sheep blood agar and then Gram-stained to demonstrate the organism.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<b>Gastrointestinal</b><br />
<br><br />
To diagnose gastrointestinal anthax, it must be distinguished from dysentery. Obtaining a history of ingesting contaminated meat can be helpful. A stool sample negative for amebic cysts or trophs and for Shigella suggest the possibility of gastrointestinal anthrax.[[#References|[6]]]<br />
<br />
<br />
<br><br />
<br />
<b>Inhalation</b><br />
<br><br />
For a patient that has inhalation anthrax, hemorrhagic mediastinitis with bloody pleural effusions will be present as well as a widened mediastinum when observed under a CT scan.<br />
[[#References|[6]]]<br />
<br />
==Treatment==<br />
For a potential exposure to anthrax, a person should remove all contaminated clothing and wash with soap and water. Medical responders need to have appropriate protection from infection which includes gloves, splash protection, and a full-face respirator. If anthrax is confirmed, antibiotics should be administered. The CDC recommends ciprofloxacin and doxycycline. If anthrax meningitis is suspected, doxycycline shouldn't be used because it does not penetrate the central nervous system very well. Pregnant or breastfeeding women can use amoxicillin. For inhalation anthrax, it is recommended to use multi-drug therapy, such as vancomycin, with the chosen antibiotic.<br />
<br />
==Prevention==<br />
Prevention methods for avoiding anthrax infection include: vaccinations, proper decontamination, and prophylactic treatments. Vaccinations exist for domestic animals and humans. Since anthrax is commonly acquired through contact with contaminated animal products, vaccination of animals is very important. Bovine anthrax vaccination is extremely effective, but usually has to be re-administered every year. Vaccination of humans is more common for bioterrorism cases, so American troops are vaccinated while it is uncommon for the general population to be vaccinated. If a human or animal has been suspected to die from anthrax, contact with the body should be avoided and the body and clothes should be burned. [[#References|[4]]]<br />
<br />
==Host Immune Response==<br />
Macrophages ingest the spores and carry them to regional lymph nodes. The <i>Bacillus</i> spores use these macrophages to bypass the immune response. Ingestion of the spores by the macrophages also induces chemokine and cytokine production which cause an inflammatory response. While neutrophils do play a role in the host immune response, alveolar macrophages (in the case of inhaled anthrax) play a more direct role with host defense of anthrax. Studies have shown that macrophages are critical to host survival during an anthrax infection. The immune system also produces anti-protective antigen (PA) immuglobulin G to combat the toxins secreted by <i>B. anthracis</i> by neutralizing lethal factor. PA-specific IgG memory B cells are also produced in infected persons and the levels of these memory cells are have been shown to be comparable or higher than those vaccinated. [[#References|[9]]] [[#References|[10]]] [[#References|[11]]]<br />
<br />
==References==<br />
<br><br />
1. [http://microbewiki.kenyon.edu Conway, Tyrrell. “Genus conway”. “Microbe Wiki” 2013. Volume 1. p. 1-2.]<br />
<br><br />
2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769905/<br />
<br><br />
3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784286/<br />
<br><br />
4. http://www.bt.cdc.gov/agent/anthrax/needtoknow.asp<br />
<br><br />
5. http://www.health.state.mn.us/divs/idepc/diseases/anthrax/anslides.pdf<br />
<br><br />
6. http://emedicine.medscape.com/article/212127-clinical<br />
<br><br />
7. http://iai.asm.org/content/49/2/291.full.pdf<br />
<br><br />
8. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2176088/<br />
<br><br />
9. http://iai.asm.org/content/74/8/4430.full<br />
<br><br />
10. http://iai.asm.org/content/74/1/469.full<br />
<br><br />
11. http://jid.oxfordjournals.org/content/190/7/1228.full<br />
<br><br />
<br />
Created by Danielle Vinnedge, student of Tyrrell Conway at the University of Oklahoma.</div>Danielle.L.Vinnedge-1