https://microbewiki.kenyon.edu/api.php?action=feedcontributions&user=Halen.M.Borron-1&feedformat=atommicrobewiki - User contributions [en]2024-03-29T08:36:40ZUser contributionsMediaWiki 1.39.6https://microbewiki.kenyon.edu/index.php?title=Mycobacterium_leprae_--_Leprosy&diff=91784Mycobacterium leprae -- Leprosy2013-07-26T11:01:12Z<p>Halen.M.Borron-1: /* Description */</p>
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<div>{{Curated}}<br />
[[Image:OUA.png|thumb|250px|center|Pathogenic Microbiology in Italy [http://cas.ou.edu/study-abroad/]]]<br />
[[Image:5.jpg|thumb|350px|right|<i>Mycobacterium leprae</i> globi in patient From: Escholarship.org [http://escholarship.org/uc/item/9m39z338/5.jpg]]]<br />
[[Image:Resized%20Possible%20image%202%20(Delhi%202011%20Peter%20Caton).jpg|thumb|350px|right| Woman with leprosy From: Leprosymission.org [http://www.leprosymission.org/assets/images/Page%20Banner%20Images/Resized%20Possible%20image%202%20(Delhi%202011%20Peter%20Caton).jpg]]]<br />
__TOC__<br />
<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Actinobacteria]]<br />
| Class = [[Actinobacteridae]]<br />
| Order = [[Actinomycetales]]<br />
| Suborder = [[Corynebacterineae]]<br />
| Family = [[Mycobacteriaceae]]<br />
| Genus = [[Mycobacterium]]<br />
| Species = [[M. leprae]] |<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=1769&lvl=3&lin=f&keep=1&srchmode=1&unlock Taxonomy] Genome: <font size="2">[http://www.ncbi.nlm.nih.gov/genome/?term=Mycobacterium+leprae Mycobacterium leprae]</font>'''<br />
|}<br />
<br />
===Description===<br />
<i>Mycobacterium leprae</i> is a microaerophilic, acid-fast bacillus which causes leprosy. Since <i>Mycobacterium leprae</i> cannot easily be cultured in the lab, much is unknown about the infectious dose, incubation, and transmission of the disease [[#References|[7]]]. The infection is thought to be spread through the skin and nasal mucosa. Humans and armadillos are the only known carriers of the disease, though there is some speculation about the possible role of insects in transmission [[#References|[8]]]. <i>Mycobacterium leprae</i> colonizes the Schwann cells of the peripheral nervous system and can also live and grow within macrophages as a way to evade the host immune system [[#References|[9]]]. The bacteria express many virulence factors that allow for invasion of the nerve cells and nutritional access [[#References|[7]]]. The symptoms of leprosy are associated with the degree of host immune system response to the infection, so the disease is classified according to these varied responses. Polar tuberculoid (TT) leprosy results from the immune system trying to kill the pathogen. This is in contrast to lepromatous (LL) which is marked by no host resistance and thus direct killing of self-cells through the immune response. Borderline categories fall between the two polar forms of the disease. Reactions can then be divided into two types based on clinical manifestations. [[#References|[10]]]. Biopsy from a lesion revealing acid-fast bacilli is necessary for diagnosis [[#References|[7]]]. The standard treatment for leprosy is a Multi-drug Treatment (MDT) that consists of steroids and antibiotics [[#References|[8]]]. Through prevention steps and treatment, the World Health Organization is attempting to eradicate the disease, and has so far succeeded in decreasing the total number of cases. However, the number of new cases each year remains the same despite some positive results from the <i>M. bovis</i> BCG vaccine. Due to the intracellular lifestyle of the bacteria, <i>Mycobacterium leprae</i> infection is associated with symptoms that are the result of the immune system attacking host cells. The bacteria are able to mount an immune response on nerve cells and other immune cells, allowing for inflammation and neuropathy [[#References|[7]]].<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
Although much about the transmission of <i>Mycobacterium leprae</i> is unknown, prolonged contact with an infected person increases an individual's chance of becoming infected. Armadillos can harbor the bacteria, but are not seen as a threat to human contraction of the disease. In addition, insects could be possible carriers of <i>Mycobacterium leprae</i> but this is unclear In humans, the bacteria is thought to be passed through skin and nasal mucosa [[#References|[8]]]. One study has demonstrated that large numbers of the bacteria can be found on the skin of infected persons, providing a possible means of transmission [[#References|[11]]]. <i>Mycobacterium leprae</i> could also be passed through nasal mucosa like the closely related <i>Mycobacterium tuberculosis</i> [[#References|[9]]].<br />
<br />
===Infectious dose, incubation, and colonization===<br />
<i>Mycobacterium leprae</i> is not able to be cultured in the lab, which can hinder studies of infectious dose and incubation, however some sources provide estimates for these categories [[#References|[7]]]. With a doubling time of 14 days [[#References|[12]]], <i>Mycobacterium leprae</i> has the longest doubling time of any studied bacteria [[#References|[9]]]. The World Health Organization states that <i>Mycobacterium leprae</i> has an incubation period of an average 5 years. Humans and armadillos are currently the only known reservoirs of the bacteria, with infected humans accounting for up to 7 billion organisms per gram of tissue [[#References|[8]]]. <i>Mycobacterium leprae</i> mostly lives in the extremities and facial region within macrophages and Schwann cells of the peripheral nervous system [[#References|[9]]].<br />
<br />
===Epidemiology===<br />
[[Image:leprosyMap.jpg|thumb|300px|left| Map of new leprosy cases annually (2010) From: Leprosymission.org [http://www.leprosymission.org/assets/images/leprosyMap.jpg]]]<br />
<i>Mycobacterium leprae</i> is thought to have originated in East Africa and spread across the globe through human migratory trends, reaching the Western world within the last 500 years [[#References|[13]]]. In 2012, the World Health Organization recorded a prevalence of approximately 180,000 cases [[#References|[8]]]. Through eradication efforts, the total number of cases worldwide has decreased, yet the number of new cases each year has remained consistent [[#References|[7]]]. Mortality is difficult to measure with leprosy, as the infection is not the immediate cause of death in many cases [[#References|[8]]].<br />
<br />
===Virulence factors===<br />
====Iron utilization====<br />
Although some genes from the closely related <i>Mycobacterium tuberculosis</i> have been deleted in <i>Mycobacterium leprae</i>, some iron utilization genes have been conserved to help the pathogen acquire nutrients for growth [[#References|[9]]]. NRAMP proteins, which are coded by one particular conserved gene, allow transportation of iron into the macrophage for survival [[#References|[14]]].<br />
<br />
====Waxy exterior====<br />
Bacteria of the <i>Mycobacterium</i> Genus are defined by their waxy exterior coat. In <i>Mycobacterium leprae</i>, the exterior allows for intake into the macrophage and into some dendritic cells, in which it can survive. The terminal mannose caps on the waxy mycobacterial ligand, lipoarabinomannan, of the pathogen are recognized by the PRR of the macrophage to allow for phagocytosis [[#References|[15]]].<br />
<br />
====Macrophage invasion====<br />
<i>Mycobacterium leprae</i> survives and replicates in macrophages, dividing to approximately 100 organisms per cell [[#References|[16]]]. The bacteria prevent phagosome and lysosome fusion to avoid degradation [[#References|[17]]]. In the event that the bacteria are absorbed into the phagolysosome, <i>Mycobacterium leprae</i> has the ability to survive emission of reactive oxygen species [[#References|[7]]].<br />
<br />
====Schwann cell invasion====<br />
The major target of <i>Mycobacterium leprae</i> is the Schwann cell [[#References|[11]]]. The optimal temperature of the bacteria corresponds to the temperature in the peripheral nerves [[#References|[18]]]. To access the cells, <i>Mycobacterium leprae</i> gets into the lymphatic system and the blood vessels [[#References|[19]]]. Once in the area, <i>Mycobacterium leprae</i> binds to the Schwann cell via laminin-binding protein [[#References|[9]]]. The bacteria are thought to then enter through the vascular epithelium into the cell [[#References|[7]]]. The infection remains localized to the peripheral nervous system by rolling and binding to exposed Schwann cells [[#References|[20]]].<br />
<br />
====Drug resistance====<br />
<i>Mycobacterium leprae</i> has many mechanisms of drug resistance to allow it to continue to survive despite antimicrobial presence [[#References|[7]]].<br />
<br />
==Clinical features==<br />
[[Image:05.05.leprosy.jpg|thumb|200px|right|Disfigurement after <i>Mycobacterium leprae</i> infection. From: Bio.davidson.edu [http://www.bio.davidson.edu/people/sosarafova/Assets/Bio307/algreer/assets/05.05.leprosy.jpg]]]<br />
===Classification===<br />
Leprosy presents with a variety of clinical features based primary on the degree to which the host immune system responds to the infection [[#References|[7]]]. In general, the disease leprosy is a result of the immune response to <i>Mycobcaterium leprae</i> invasion of the Schwann cells, which leads to demyelination neuropathy [[#References|[21]]]. Common results of the immune response are loss of sensation and disfiguration [[#References|[9]]]. Chronic inflammation can lead to this paralysis, specifically along the periphery, and can also affect facial regions, contributing to factors such as blindness [[#References|[7]]]. Classification of leprosy is based of a five part system which divides patients by immune response. There are two polar categories and three borderline types which fall between the polar classifications. One polar type is called tuberculoid (TT). This type is marked by a high level of cellular immune response, delayed hypersensitivity, and bacilli in biopsied tissue. The other extreme is called lepromatous (LL). In this type of leprosy, there is no host resistance. Nodular lesions will form all over body, and when biopsied, they reveal globi, or bundles of bacilli. The remaining three types are borderline categories, being closer to one polar type or the other, or having marks of both polar types. These are borderline lepromatous (BL), mid-borderline (BB), and borderline tuberculoid (BT) [[#References|[10]]]. <br />
<br />
<br>Clinical manifestations can be divided into two major categories: Type 1 and Type 2 reactions.<br />
<br />
===Type 1===<br />
Borderline leprosy types (BL, BB, and BT) are included in this classification. The symptoms include lesions that are red and hardened, fluid accumulation in the periphery, sensory loss, and neuropathy. Symptoms develop gradually and may last for several weeks [[#References|[7]]].<br />
<br />
===Type 2===<br />
Erythema nodosum leprosum, or Type 2 reactions, affect multibacillary patients (LL and BL). In contrast to Type 1 reactions, symptoms develop suddenly, subside after a couple weeks, and may reoccur many times over a period of months. Tender, red lesions erupt on the face, extremities, and trunk. These patients may develop inflammation of the eyes leading to blindness and other complications. General muscle inflammation, joint inflammation, and orchitis may occur [[#References|[7]]]. <br />
===Lucio Phenomenon===<br />
The Lucio Phenomenon is a rare form of symptoms that describes a rapid onset of inflammation of the blood vessel walls and anemia. This rarity occurs primarily in Mexican leprosy patients [[#References|[22]]].<br />
<br />
==Diagnosis==<br />
Diagnosis is typically made upon recognition of acid-fast bacilli in a skin biopsy of a lesion [[#References|[7]]]. As some patients have few lesions, scientists are looking for immunodiagnostic tests to explain neuropathy and other symptoms that may be unaccompanied by lesions [[#References|[9]]]. For instance, tuberculoid leprosy (TT) often produces few lesions, so the disease can misdiagnosed. In lepromatous (LL) cases, biopsy should be made from a nerve cell to rule out alternative diagnoses which might show similar symptoms and bacilli in tissue [[#References|[7]]].<br />
<br />
==Treatment==<br />
[[Image:5.Jesuraj-Before%20&%20After%20Treatment.jpg|thumb|250px|left| Before and after Multidrug Therapy (MDT) From: Stlukesleprosyhospital.org [http://www.stlukesleprosyhospital.org/5.Jesuraj-Before%20&%20After%20Treatment.jpg]]]<br />
The current standard treatment for <i>Mycobacterium leprae</i> infection is a Multi-drug Treatment (MDT) which consists of corticosteroids and antimicrobials. For paucibacillary leprosy, rifampicin and dapsone are used, while rifampicin, clofazimine, and dapsone are used in multibacillary leprosy. Rifampicin, ofloxacin, and minocycline can be combined in single lesion paucibacillary leprosy. Oral prednisolone can be used in secondary complications such as neuropathy and eye problems. Drops can be used to dilate the eye and stimulate relaxation to help the healing process [[#References|[8]]]. However, scientists are discovering drug-resistant strains of <i>Mycobacterium leprae</i>, so precautions must be taken [[#References|[7]]]. Minocycline or ofloxacin can be used in the event of a rifampicin allergy, resistance, or presence of a disease antagonistic to rifampicin. Interestingly, the disease can sometimes be self-limiting and cure itself independently of drug treatment [[#References|[8]]].<br />
<br />
==Prevention==<br />
===Vaccination===<br />
A proper vaccination for <i>Mycobacterium leprae</i> would provide protective immunity. One vaccine has shown positive results in protecting the inoculated person from infection. The M. bovis BCG vaccine proved effective in India [[#References|[23]]] and Brazil [[#References|[24]]]. <br />
===Eradication attempts===<br />
Global efforts to eradicate leprosy has resulted in elimination of the disease from 119 of 122 countries thought to be highly affected [[#References|[8]]]. With proper prevention measures, early detection, and treatment, numbers of new cases would decrease and those already infected could be cured [[#References|[9]]].<br />
<br />
==Immune Response==<br />
===Protective immunity and susceptibility===<br />
Science has discovered that over 95 percent of people could be immune to leprosy, due to protection and exposure [[#References|[7]]]. However, some populations may be more susceptible to the disease based on genetic factors. The PARK2/PACRG gene could contribute to susceptibility to <i>Mycobacterium leprae</i> infection [[#References|[25]]]. In addition, the Vitamin D receptor (VDR) gene is associated with both polar types of the disease [[#References|[26]]]. Innate immunity can fail in an instance of susceptibility, so the adaptive immune response works to eradicate the infection through T cells [[#References|[7]]].<br />
===Host defense===<br />
The symptoms associated with <i>Mycobacterium leprae</i> infection, such as lesions and neuropathy, are typically results of the host attacking its own nerve cells through an immune response. While the bacteria can trigger apoptosis in the cells, the body also contributes to cell death by mounting an immune response on the infected cells. Dendritic cells phagocytose the pathogen to stimulate the adaptive immune response through T cells [[#References|[7]]]. In tuberculoid leprosy, CD4 T cells are most prevalent, whereas CD8 cytotoxic T cells are in higher numbers in lepromatous leprosy [[#References|[28]]]. The T cells, specifically the cytotoxic cells, kill the infected Schwann cells, which results in sensory loss [[#References|[27]]]. As well, infected Schwann cells and macrophages can be attacked by NK cells [[#References|[29]]], [[#References|[30]]]. Toll-like receptors (TLRs) also have an important function in the immune response, but specifically for distinguishing between polar types of the disease. Tissue biopsies showed that tuberculoid patients produced stronger TLRs on leukocytes than the lepromatous type, suggesting that TLRs significantly affect the ability of the immune system to recognize the bacteria to avoid killing host cells [[#References|[31]]]. TLRs are also associated with the cytokine TNF-α which causes tissue damage in leprosy [[#References|[32]]]. TNF-α is produced by macrophages, and is used to stimulate T cell mediated immunity, which causes many symptoms of the disease [[#References|[7]]]. This suggests that tuberculoid leprosy (TT) may share similar symptoms to lepromatous leprosy (LL) despite varied immune responses due to the effects of cytokines. The immune system also can work to deter bacteria from adhering to the nerve cells using antibodies directed at the outer coat of <i>Mycobacterium leprae</i> cells [[#References|[33]]].<br />
<br />
===Bacterial evasion===<br />
Many of the aforementioned virulence factors of <i>Mycobacterium leprae</i> are associated with the ability to evade the host immune response, such as living and surviving within macrophages through various mechanisms. The bacteria also suppress the immune system by directly affecting the dendritic cells. T cell mediated immune response can be halted by preventing the interaction of dendritic cells and T cells, which <i>Mycobacterium leprae</i> accomplishes by causing the dendritic cell to express PGL-1 on its surface. This protein appears to alter dendritic cell and T cell matching, and thus slows the immune attack on the bacteria [[#References|[34]]]. The bacteria can also stop dendritic cell maturation by preventing IL-2 production, further disabling the immune defenses [[#References|[35]]].<br />
<br />
==References==<br />
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<br>31 [http://www.jimmunol.org/content/170/7/3451.abstract?ijkey=95edbeb1e6df27135efb4a7a8583a55e594ad0d7&keytype2=tf_ipsecsha Bochud, P.Y., Hawn, T.R., and A. Aderem. "Cutting edge: a Toll-like receptor 2 polymorphism that is associated with lepromatous leprosy is unable to mediate mycobacterial signaling." J. Immunol. 170. 3451-3454. 2003.]<br />
<br>32 [http://www.pnas.org/content/96/25/14459.abstract?ijkey=9a17440778f0c30119d332d0a744003ef443a0b3&keytype2=tf_ipsecsha Underhill, D.M., Ozinsku, A., Smith, K.D., and A. Aderem. "Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signals in macrophages." Proc. Natl. Acad. Sci. USA 96:14459-14463. 1999.]<br />
<br>33 [http://www.ncbi.nlm.nih.gov/pubmed/2683036?dopt=Abstract Choudhury, A., Mistry, N.F., and N.H. Antia. "Blocking of Mycobacterium leprae adherence to dissociated Schwann cells by anti-mycobacterial antibodies." Scand. J. Immunol. 30. 505-509. 1989.]<br />
<br>34 [http://iai.asm.org/content/70/9/5167.abstract?ijkey=41f1c0d3ea24c63222b079d7e26688c12c19c14b&keytype2=tf_ipsecsha Hashimoto, K., Maeda, Y., Kimura, H., Suzuki, K., Masuda, A., Matsuoka, M., and M. Makino. "Mycobacterium leprae infection in monocyte-derived dendritic cells and its influence on antigen-presenting function." Infect. Immun. 70. 5167-5176. 2002.]<br />
<br>35 [http://www.jimmunol.org/content/166/12/7477.abstract?ijkey=2cd9a3a90c101d821d5ea7efd9a16784e5812011&keytype2=tf_ipsecsha Nigou, J., Zelle-Rieser, C., Gilleron, M., Thurnher, M., and G. Puzo. "Mannosylated lipoarabinomannans inhibit IL-12 production by human dendritic cells: evidence for a negative signal delivered through the mannose receptor." J. Immunol. 166. 7477-8485. 2001.]<br />
<br />
<br />
Created by Gracen Conway, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91713Lyme disease2013-07-25T10:36:57Z<p>Halen.M.Borron-1: /* Virulence Factors */</p>
<hr />
<div>{{Curated}}<br />
[[Image:OUA.png|thumb|240px|center|Microbiology in Italy[http://cas.ou.edu/study-abroad/]]]<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
====Immune System Avoidance====<br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
====Motility, Adhesins, and Chemotaxis====<br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
====Quorum Sensing and Biofilms====<br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[8]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[9]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[10]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[3]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria Lyme Disease Bacteria. A Practical Guide to Lyme Disease.]<br />
<br /><br /> 2 [http://www.cdc.gov/lyme/transmission/index.html Transmission. Centers for Disease Control (CDC).]<br />
<br /><br /> 3 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, JD, Caimano MJ, Stevenson B, Linden TH. Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes. Nature.]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis Rassbach C, Jantausch B. Reviewing Lyme Disease with Facial Palsy and Meningitis. Infectious Disease in Children.]<br />
<br /><br /> 5 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 Berndtson K. Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease.]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ Signs and Symptoms of Lyme Disease. CDC.]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full Kugeler K, Griffith K, Gould H, Kochanek K, Delorey MJ, Biggerstaff BJ, Mead PS. A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States. Clinical Infectious Disease.]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full Wormser G, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler JS, Nadelman RB. The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Infectious Diseases Society of America.]<br />
<br /><br /> 9 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm Vaccines. CDC.]<br />
<br /><br /> 10 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial.]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91704Lyme disease2013-07-25T10:13:23Z<p>Halen.M.Borron-1: </p>
<hr />
<div>{{Curated}}<br />
[[Image:OUA.png|thumb|240px|center|Microbiology in Italy[http://cas.ou.edu/study-abroad/]]]<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[8]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[9]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[10]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[3]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria Lyme Disease Bacteria. A Practical Guide to Lyme Disease.]<br />
<br /><br /> 2 [http://www.cdc.gov/lyme/transmission/index.html Transmission. Centers for Disease Control (CDC).]<br />
<br /><br /> 3 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, JD, Caimano MJ, Stevenson B, Linden TH. Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes. Nature.]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis Rassbach C, Jantausch B. Reviewing Lyme Disease with Facial Palsy and Meningitis. Infectious Disease in Children.]<br />
<br /><br /> 5 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 Berndtson K. Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease.]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ Signs and Symptoms of Lyme Disease. CDC.]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full Kugeler K, Griffith K, Gould H, Kochanek K, Delorey MJ, Biggerstaff BJ, Mead PS. A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States. Clinical Infectious Disease.]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full Wormser G, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler JS, Nadelman RB. The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Infectious Diseases Society of America.]<br />
<br /><br /> 9 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm Vaccines. CDC.]<br />
<br /><br /> 10 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial.]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91702Lyme disease2013-07-25T10:05:50Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[8]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[9]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[10]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[3]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria Lyme Disease Bacteria. A Practical Guide to Lyme Disease.]<br />
<br /><br /> 2 [http://www.cdc.gov/lyme/transmission/index.html Transmission. Centers for Disease Control (CDC).]<br />
<br /><br /> 3 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, JD, Caimano MJ, Stevenson B, Linden TH. Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes. Nature.]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis Rassbach C, Jantausch B. Reviewing Lyme Disease with Facial Palsy and Meningitis. Infectious Disease in Children.]<br />
<br /><br /> 5 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 Berndtson K. Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease.]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ Signs and Symptoms of Lyme Disease. CDC.]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full Kugeler K, Griffith K, Gould H, Kochanek K, Delorey MJ, Biggerstaff BJ, Mead PS. A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States. Clinical Infectious Disease.]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full Wormser G, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler JS, Nadelman RB. The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Infectious Diseases Society of America.]<br />
<br /><br /> 9 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm Vaccines. CDC.]<br />
<br /><br /> 10 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial.]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91698Lyme disease2013-07-25T09:59:34Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[8]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[9]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[10]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[3]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 3 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis Rassbach, Caroloine, Barbara Jantausch. "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Infectious Disease in Children"]<br />
<br /><br /> 5 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 Berndtson, Keith. "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ "Signs and Symptoms of Lyme Disease" "CDC"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full Kugeler, Kierston, Keith Griffith, Hannah Gould, Ken Kochanek, Mark J. Delorey, Brad J. Biggerstaff, Paul S. Mead. "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full Wormser, Gary, Raymond J. Dattwyler, Eugene D. Shapiro, John J. Halperin, Allen C. Steere, Mark S. Klempner, Peter J. Krause, Johan S. Bakken, Franc Strle, Gerold Stanek, Linda Bockenstedt, Durland Fish, J. Stephen Dumler, Robert B. Nadelman. "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America" "Infectious Diseases Society of America"]<br /><br /> 9 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 10 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91697Lyme disease2013-07-25T09:57:35Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[8]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[9]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[10]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[3]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 3 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis Rassbach, Caroloine, Barbara Jantausch. "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Infectious Disease in Children"]<br />
<br /><br /> 5 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 Berndtson, Keith. "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ "Signs and Symptoms of Lyme Disease" "CDC"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full Kugeler, Kierston, Keith Griffith, Hannah Gould, Ken Kochanek, Mark J. Delorey, Brad J. Biggerstaff, Paul S. Mead. "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America" "Infectious Diseases Society of America"]<br /><br /> 9 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 10 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91695Lyme disease2013-07-25T09:55:34Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[8]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[9]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[10]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[3]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 3 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis Rassbach, Caroloine, Barbara Jantausch. "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Infectious Disease in Children"]<br />
<br /><br /> 5 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 Berndtson, Keith. "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ "Signs and Symptoms of Lyme Disease" "CDC"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America" "Infectious Diseases Society of America"]<br /><br /> 9 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 10 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91693Lyme disease2013-07-25T09:54:43Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[8]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[9]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[10]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[3]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 3 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis Rassbach, Caroloine, Barbara Jantausch. "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Infectious Disease in Children"]<br />
<br /><br /> 5 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ "Signs and Symptoms of Lyme Disease" "CDC"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America" "Infectious Diseases Society of America"]<br /><br /> 9 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 10 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91689Lyme disease2013-07-25T09:53:31Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[8]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[9]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[10]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[3]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 3 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Infectious Disease in Children"]<br />
<br /><br /> 5 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ "Signs and Symptoms of Lyme Disease" "CDC"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America" "Infectious Diseases Society of America"]<br /><br /> 9 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 10 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91684Lyme disease2013-07-25T09:51:22Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[8]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[9]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[10]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[3]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 3 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ "Signs and Symptoms of Lyme Disease" "CDC"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America" "Infectious Diseases Society of America"]<br /><br /> 9 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 10 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91679Lyme disease2013-07-25T09:48:09Z<p>Halen.M.Borron-1: /* Host Immune Response */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[8]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[9]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[10]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[3]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ "Signs and Symptoms of Lyme Disease" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America" "Infectious Diseases Society of America"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91677Lyme disease2013-07-25T09:47:22Z<p>Halen.M.Borron-1: /* Immunization */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[8]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[9]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[10]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[2]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ "Signs and Symptoms of Lyme Disease" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America" "Infectious Diseases Society of America"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91674Lyme disease2013-07-25T09:46:38Z<p>Halen.M.Borron-1: /* Treatment */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[8]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[2]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ "Signs and Symptoms of Lyme Disease" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America" "Infectious Diseases Society of America"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91673Lyme disease2013-07-25T09:46:06Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[2]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ "Signs and Symptoms of Lyme Disease" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://cid.oxfordjournals.org/content/43/9/1089.full "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America" "Infectious Diseases Society of America"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91671Lyme disease2013-07-25T09:41:10Z<p>Halen.M.Borron-1: /* Symptoms */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite [[#References|[6]]]. The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[2]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ "Signs and Symptoms of Lyme Disease" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91669Lyme disease2013-07-25T09:40:41Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[2]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.cdc.gov/lyme/signs_symptoms/ "Signs and Symptoms of Lyme Disease" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91666Lyme disease2013-07-25T09:38:49Z<p>Halen.M.Borron-1: /* Virulence Factors */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[5]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[5]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[5]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[2]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91665Lyme disease2013-07-25T09:38:04Z<p>Halen.M.Borron-1: /* Epidemiology */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[3]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[2]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[2]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[7]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[7]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[7]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[2]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91663Lyme disease2013-07-25T09:37:46Z<p>Halen.M.Borron-1: /* Infectious Dose, Incubation Period, and Colonization */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[3]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[3]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[2]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[2]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[7]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[7]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[7]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[2]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91659Lyme disease2013-07-25T09:35:56Z<p>Halen.M.Borron-1: /* Transmission */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[2]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[3]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[2]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[2]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[7]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[7]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[7]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[2]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91656Lyme disease2013-07-25T09:34:13Z<p>Halen.M.Borron-1: /* Epidemiology */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[3]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[2]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[2]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[7]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[7]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[7]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[2]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91652Lyme disease2013-07-25T09:33:24Z<p>Halen.M.Borron-1: /* Virulence Factors */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[2]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[2]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[7]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[7]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[7]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[2]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91650Lyme disease2013-07-25T09:32:27Z<p>Halen.M.Borron-1: /* Host Immune Response */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[7]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[7]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[7]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[2]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91648Lyme disease2013-07-25T09:31:52Z<p>Halen.M.Borron-1: /* Infectious Dose, Incubation Period, and Colonization */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days [[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[7]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[7]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[7]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[3]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91630Lyme disease2013-07-25T09:17:17Z<p>Halen.M.Borron-1: /* Host Immune Response */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[7]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[7]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[7]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
The host immune response is important in the virulence of <i>B. burgdorferi</i> because the bacteria exploit the immune system to persist in the host. This exploitation causes the symptoms seen in the host. When a tick imbeds in the host, spirochaetes will be released 36-48 hours later. Once a spirochaete enters, macrophages will be onsite to destroy the invader. The bacteria can avoid this by changing up its PAMPs which allow the macrophage to detect it. If a macrophage does detect the pathogen, it will send out cytokines, chemokines, and lipid mediators to activate inflammation. Inflammation is the cause of the characteristic bull's eye rash seen in the host. Neutrophils are generally the second leukocyte to arrive to the infection, but <i>B. burgdorferi</i> produces sialostatin L which effects neutrophil chemotaxis [[#References|[3]]]. Without neutrophils, the immune system is racing to keep up with the infection. This is a significant factor in the immune system failing to contain the infection. SALP15 is a molecule produced by tick saliva and it aids in inhibiting killing of the spirochaete through antibodies. The molecule binds to the bacteria. Complement pathway is another agent used by the immune system to kill pathogens, but <i>B. burgdorferi's</i> BbCRASPs can bind to complement H factor which prevents the pathway from activating. With reduced effectiveness of macrophages, neutrophils, complement, and antibodies leads to the failure of the immune system and production of symptoms with this infection.<br />
<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91615Lyme disease2013-07-25T09:04:44Z<p>Halen.M.Borron-1: /* Virulence Factors */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. The tactics used by this spirochaete involve survival more than outright destruction of host cells. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[7]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[7]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />The bacteria can also engage in quorum sensing and biofilm development. The biofilm can help protect the bacteria from the immune system as well as antibiotics. Quorum sensing involves microbes sensing cell density thresholds and releasing signals to other cells to alter gene expression [[#References|[7]]]. Biofilms allow bacteria at the bottom to survive antibiotics because lower concentrations will reach them.<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91611Lyme disease2013-07-25T08:57:41Z<p>Halen.M.Borron-1: /* Virulence Factors */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />About 6% of this bacteria's genome is devoted to the important virulence factor motility [[#References|[7]]]. This spirochaete uses a rotor mechanism to propel itself through blood, but the unique portion of its motility is the set of ribbons in its periplasmic space. Another important portion of its motility are the twin motors on either end of the flagella. The extremely fast motility of this organism allows it to escape phagocytosis of large cells such as the macrophage. Another virulence factor is the use of adhesins such as integrins, proteoglycans, laminin, and fibronectin. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[7]]]. Once the bacteria begins moving from the blood stream, the utilization of this enzyme becomes important in making a pathway to the extracellular matrix. While in the extracellular matrix, the bacteria can more easily hide from the immune system because there are less leukocytes in this tissue. <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. Methylcellulose and hyaluronic acid which are found in the extraceullular matrix are known chemoattractants of this spirochaete. <br />
<br />biofilm development and quorum sensing<br />
<br />differ spirochaetal form<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91605Lyme disease2013-07-25T08:47:00Z<p>Halen.M.Borron-1: /* Virulence Factors */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
Once <i>B. burgdorferi</i> enters the host, the main goal is immune system avoidance through various virulence factors. The bacteria does not secret any toxins and its virulence comes from the exploitation of the immune system. The inflammation the immune system produces in response to this bacteria results in the disease. <br />
<br />One of the main virulence factors of this bacteria is its continuous variation of its surface antigens. The lipoprotein VlsE does this through recombination of silent cassettes [[#References|[3]]]. This virulence factor significantly reduces the effectiveness of the adaptive immune system in responding to the invader. <br />
<br /><i>B. burgdorferi</i> also uses the tactic of binding to complement H factor through BbCRASPs [[#References|[3]]]. These H factors are used by the host immune system to avoid activating complement for self cells. By exploiting this factor, the bacteria can avoid lysis by the alternative complement pathway. This reduces the effectiveness of the innate immune system in destruction of the pathogen. <br />
<br />The impediment of the generation of reactive oxygen species and chemotaxis of neutrophils can contribute to the bacteria's avoidance of phagocytosis. By avoiding this process of destruction, the bacteria can then spread to other parts of the body. <br />
<br />Motility and adhesins become important <br />
<br />The bacteria have a two-component chemotaxis system called CheA-CheY. This system can signal to the flagellar motors when environmental signals are detected. These signals can either be favorable, such as nutrient detection, or non-favorable such as repellant molecules. <br />
<br />The lipoprotein OspC is important to the bacteria in using plasminogen, which can digest fibrin and large glycoproteins [[#References|[7]]]. <br />
<br />biofilm development and quorum sensing<br />
<br />differ spirochaetal form<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91588Lyme disease2013-07-25T08:10:54Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br /><br /> 8 [http://www.ncbi.nlm.nih.gov/pubmed/23637552 "Review of Evidence for Immune Evasion and Persistant Infection in Lyme Disease"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91587Lyme disease2013-07-25T08:07:15Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"]<br />
<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91586Lyme disease2013-07-25T08:06:59Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br /><br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br />
<br /><br /> 7 [http://cid.oxfordjournals.org/content/52/3/364.full "A Review of Death Certificates Listing Lyme Disease as a Cause of Death in the United States" "Clinical Infectious Disease"<br />
<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91585Lyme disease2013-07-25T08:05:46Z<p>Halen.M.Borron-1: /* Morbidity and Mortality */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
Lyme disease effects 60,000 people worldwide per year, but mortality of this disease is low. Secondary consequences of the disease such as cardiac and neurological problems are most often listed along with Lyme disease as the cause of death. Mortality rates in the United States include 114 people from 1999-2003 [[#References|[7]]].<br />
<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br />,br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91577Lyme disease2013-07-25T07:49:19Z<p>Halen.M.Borron-1: /* Treatment */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
Typical treatments for the early localized stage or early disseminated stage of Lyme disease include, doxycycline, amoxicillin, or cefuroxime axetil antibiotics [[#References|[7]]]. For late disseminated stage where patients have developed neurological or cardiac forms of the disease, ceftriaxone or penicillin antibiotics may be used.<br />
<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br />,br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91573Lyme disease2013-07-25T07:41:39Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"]<br />
<br />,br /> 6 [http://www.ncbi.nlm.nih.gov/pubmed/23665341 Wressnigg N, Pollabauer EM, Alchinger G. "Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial"]<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91572Lyme disease2013-07-25T07:38:39Z<p>Halen.M.Borron-1: /* Immunization */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]]. Currently, researchers are in phase two for a promising new vaccine that targets the OspA protein of <i>B. burgdorferi</i> [[#References|[6]]]. The problem with previous vaccine attempts was the range of species of Borrelia that cause Lyme and the different surface proteins that cover them. This new vaccine reengineered OspAs to include components of all known species of Borrelia.<br />
<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91570Lyme disease2013-07-25T07:30:32Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]].<br />
<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br /><br /> 5 [http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm "Vaccines" "CDC"<br />
<br /><br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91569Lyme disease2013-07-25T07:29:37Z<p>Halen.M.Borron-1: /* Immunization */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
A vaccine for the disease was released but pulled from the market in 2002 citing low demand [[#References|[5]]].<br />
<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br />,br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91568Lyme disease2013-07-25T07:27:35Z<p>Halen.M.Borron-1: /* Risk Avoidance */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks. Landscaping can also help to keep ticks out of yards and in public places. Pest management is another tool that can be utilized to prevent the spread of Lyme disease.<br />
<br />
===Immunization===<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br />,br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91563Lyme disease2013-07-25T07:23:46Z<p>Halen.M.Borron-1: /* Risk Avoidance */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
To avoid contracting Lyme disease, the central place to be cautious would be in wooded areas with high grass. Repelling ticks with DEET (N, N-diethyl-m-toluamide) is a good option if a wooded area is nearby or one has been entered recently. Always check children for ticks paying special attention to the hairline and hard to see places. Use a mirror to check yourself for ticks. Permethrin treated clothing is also available to repel ticks.<br />
<br />
===Immunization===<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br />,br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91545Lyme disease2013-07-25T07:11:34Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
===Immunization===<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
<br />,br />Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91544Lyme disease2013-07-25T07:11:12Z<p>Halen.M.Borron-1: /* References */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
===Immunization===<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [http://www.ncbi.nlm.nih.gov/pubmed/22230951 Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis "Reviewing Lyme Disease with Facial Palsy and Meningitis" "Healio"]<br />
Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91542Lyme disease2013-07-25T07:07:15Z<p>Halen.M.Borron-1: /* Diagnosis */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
===Immunization===<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis]<br />
Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91541Lyme disease2013-07-25T07:06:27Z<p>Halen.M.Borron-1: /* Diagnosis */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
If the characteristic bull’s eye rash is detected, the diagnosis of Lyme disease may be made [[#References|[4]]]. If no rash is present, other laboratory tests must be carried out to determine if the disease is present. Three to six weeks after the bite occurred, an enzyme immunoassay or immunofluorescent test may be done to test the level of Lyme IgM or IgG in the blood. If this is positive, a Western blot can be ordered to detect IgM or IgG antibody levels. Both of these positive test would indicate Lyme disease. If the disease is in the last stage and involving the central nervous system, clinical presentation is the only indicator of disease.<br />
<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
===Immunization===<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis]<br />
Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91058Lyme disease2013-07-23T17:21:00Z<p>Halen.M.Borron-1: /* Epidemiology */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common vector-borne illness in the world [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. Nearly 30,000 cases were confirmed in 2008 in the United States with 60,000 cases occurring worldwide [[#References|[2]]]. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
===Immunization===<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis]<br />
Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91051Lyme disease2013-07-23T17:10:06Z<p>Halen.M.Borron-1: /* Description */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. <i>B. garinii</i> and <i>B. afzelii</i> are Lyme disease causing strains that inhabit Eurasia while <i>B. burgdorferi</i> typically inhabits North America. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common tick-borne illness in the United States [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
===Immunization===<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis]<br />
Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91048Lyme disease2013-07-23T17:03:02Z<p>Halen.M.Borron-1: /* Infectious Dose, Incubation Period, and Colonization */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
Unfortunately, the infectious dose for Lyme disease is unknown. The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptom shown after the incubation period is usually the bull's eye rash, but this is not always the case. Other, less recognizable, symptoms can occur such as fever and fatigue. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common tick-borne illness in the United States [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
===Immunization===<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis]<br />
Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Lyme_disease&diff=91047Lyme disease2013-07-23T17:01:01Z<p>Halen.M.Borron-1: /* Transmission */</p>
<hr />
<div>{{Curated}}<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Spirochaetes]]<br />
| Class = [[Spirochaetia]]<br />
| Order = [[Spirochaetales]]<br />
| Family = [[Spirochaetaceae]]<br />
| Genus = [[Borrelia]]<br />
| species = [[burgdorferi]]<br />
<br />
===Description=== <br />
Lyme disease is caused by the bacteria <i>Borrelia burgdorferi</i> sensu lato. Because the bacteria has a number of hybrid strains that also cause Lyme disease, <i>Borrelia burgdorferi</i> sensu lato is used to refer to all Lyme disease causing strains. Different strains may cause slightly different symptoms in the host. This disease was first isolated in 1975 by Allen Steere in Old Lyme, Connecticut. Willy Burgdorfer isolated the bacteria from Ixodes ticks (deer ticks) which caused an immune response in the immune serum of diagnosed patients [[#References|[1]]]. <i>B. burgdorferi</i> are microaerophilic, spirochaetes. A key to the pathogen’s virulence is that it does not require iron to survive. Instead, the bacteria has evolved to use magnesium. If detected early, antibiotics can be administered and the infection will cease. But if left untreated, serious symptoms may arise such as joint pain, sleep disturbance, and neurological problems. The disease is the most common in summer months and early fall.<br />
<br />
==Pathogenesis==<br />
===Transmission===<br />
[[Image:Lyme_Cycle.jpeg|thumb|200px|right| Depiction of the lyme disease life cycle From: Nature [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]]<br />
Lyme disease is a zoonosis that is typically transmitted via ticks of the Ixodes genus such as the deer tick [[#References|[3]]]. To initiate infection, the tick must bite the host and the saliva of the tick containing the spirochaetes will enter the host. Transmission typically occurs via nymph ticks, but may occur with ticks of any life stage. Nymph ticks are the most likely transmitter because they are small and not easily detectable by humans. Once attached to the host, the tick must remain there for 36-48 hours to transmit <i>B. burgdorferi</i> to the host. Infection usually occurs during spring and summer months in wooded areas where Ixodes nymph ticks are prominent. White footed mice are the natural reservoirs of this disease. A nymph tick is uninfected with the spirochaete until it feeds on an infected animal. Once infected the tick will more on to infect more hosts.<br />
<br />
===Infectious Dose, Incubation Period, and Colonization===<br />
The incubation period for <i>B. burgdorferi</i> is 3-32 days[[#References|[2]]]. The first symptoms shown after the incubation period is usually the bull's eye rash, but this is not always the case. The bacteria typically colonizes skin tissue first, but can move on to colonize the heart, peripheral and central nervous system and large joints. Colonization is directed by the detection of required nutrients such as glucose, amino acids, N-acetyl-glucosamine, and long chain fatty acids. After prolonged exposure, the spirochaetes usually begin to infect the extracellular matrix of the host which provides the bacteria extra protection from the host immune response.<br />
<br />
===Epidemiology===<br />
[[Image:Lyme_Map.jpeg|thumb|200px|right| Map of lyme disease outbreaks in United States From: CDC [http://thehandwrittenlife.wordpress.com/2013/02/21/what-is-lyme-disease/]]] Lyme disease is the most common tick-borne illness in the United States [[#References|[4]]]. Most outbreaks of this disease in the United States occur in the Northeast usually from Maine to Virginia. Outbreaks have occurred in other states such as Wisconsin, Minnesota, California, and Oregon. The most commonly effected age group is 5 to 9 years old.<br />
<br />
===Virulence Factors===<br />
[[Image:Lyme_flagella.jpeg|thumb|200px|right| Structure of <i>Borrelia burgdorferi</i> From: Nature [http://www.nature.com/nrmicro/journal/v3/n2/full/nrmicro1086.html]]]<br />
<br />
==Clinical features==<br />
===Symptoms===<br />
Symptoms of Lyme disease can develop in three stages. Stage 1 is the early localized stage which can occur 3-32 days after a tick bite (CDC, symptoms). The characteristic symptom of this stage is the bull's eye rash (erythema migrans) on the skin where the bite occurred. Only 70-80% of infected people get this rash and the rash can be delayed up to 32 days after the tick bite has occurred. These factors can lead to the disease being undiagnosed. Other symptoms of this stage typically include fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. <br />
<br /><br />Stage 2 is the early disseminated stage which can occur days to weeks after the tick bite. After time has passed the bacteria can spread to various sites in the body which produces different symptoms in the host. Some of these symptoms include additional bull's eye rashes, facial or bell's palsy, severe headaches, meningitis, pain and swelling in joints, radiculopathy, arthralgia, heart palpitations and dizziness. Meningitis could result from the bacteria spreading to the spinal cord and causing inflammation of the meninges. This is generally not fatal. <br />
<br /><br />Stage 3 is the late disseminated stage which can occur months to years after the tick bite. Patients that go without treatment may begin to have arthritis, with severe joint pain and swelling. Large joints are often effected in this type of arthritis. This stage occurs in approximately 60% of untreated patients. Up to 5% of untreated patients may develop chronic neurological complaints such as shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.<br />
<br /><br />About 10% of patients that undergo antibiotic treatment develop post-treatment Lyme disease syndrome (PTLDS). Symptoms include muscle and joint pain, cognitive defects, sleep disturbance, and fatigue. This disease may be due to the host's immune response continuing after the infection has been cleared.<br />
<br />
===Morbidity and Mortality===<br />
==Diagnosis==<br />
==Treatment==<br />
==Prevention==<br />
===Risk Avoidance===<br />
===Immunization===<br />
==Host Immune Response==<br />
==References==<br />
1 [http://lymediseaseguide.org/lyme-disease-bacteria "Lyme Disease Bacteria." "A Practical Guide to Lyme Disease."]<br />
<br /><br /> 2 [Radolf, Justin D. Melissa J. Caimano, Brian Stevenson, Linden T. Hu. "Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes." "Nature."]<br />
<br /><br /> 3 [http://www.cdc.gov/lyme/transmission/index.html "Transmission" "CDC"]<br />
<br /><br /> 4 [http://www.healio.com/pediatrics/emerging-diseases/news/print/infectious-diseases-in-children/%7B6babf10e-8f11-49b2-b599-6aff3f2e751a%7D/reviewing-lyme-disease-with-facial-palsy-and-meningitis]<br />
Created by {Halen Borron}, student of Tyrrell Conway at the University of Oklahoma.</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Clostridium_difficile-associated_disease&diff=90951Clostridium difficile-associated disease2013-07-23T12:30:40Z<p>Halen.M.Borron-1: /* Moderate to severe cases */</p>
<hr />
<div>{{Curated}}<br />
[[Image:OULOGOBIANCO.JPEG|thumb|230px|left|University of Oklahoma Study Abroad Microbiology in Arezzo, Italy[http://cas.ou.edu/study-abroad/]]]<br />
[[File:Clostridium difficile spore.gif|400px|thumb|right|Scanning electron microscope image of <i>Clostridium difficile</i>. From: Bioquell.com [http://www.bioquell.com/technology/microbiology/clostridium-difficile/]]]<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Firmicutes]]<br />
| Class = [[Clostridia]]<br />
| Order = [[Clostridiales]]<br />
| Family = [[Clostridiaceae]]<br />
| Genus = [[Clostridium]]<br />
| species = [[Clostridium difficile]]<br />
<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=1496&lvl=3&lin=f&keep=1&srchmode=1&unlock Taxonomy] Genome: <font size="2">[http://www.ncbi.nlm.nih.gov/genome/?term=clostridium+difficile Genome]</font>'''<br />
|}<br />
<br />
===Description===<br />
<i>Clostridium difficile</i> causes pseudomembranous colitis, toxic megacolon, perforations of the colon, sepsis, and, on occasion, death. It is a Gram-positive, spore-forming rod that is an obligate anaerobe. It can be found in soil, water, feces, and the human gut. <i>C. difficile</i> is a normal inhabitant of the gut microbial community of about 1-3% of adults. The pathogenic form of <i>C. difficile</i> is transferred via the fecal-oral route as well as through spore dispersal. <i>Clostridium difficile</i>-associated disease (CDAD) was initially reported approximately 30 years ago. The CDC first recorded infections from a hyper-virulent strain in 2000 along with a marked increase in the number of CDAD infections. <i>C. difficile</i> causes disease by producing the toxins TcdA and TcdB that function to disrupt protein synthesis within the host cell. The toxins are responsible for producing symptoms such as watery diarrhea, fever, loss of appetite, nausea, and severe abdominal pain [[#References|[1]]]. Although <i>C. difficile</i> only causes about 20% of antibiotic associated colitis, standard treatments fail in about 25% of CDAD cases. Patients treated promptly typically recover. However, CDAD is notorious for recurrence after initial antibiotic treatment. 33% of patients with an infection will have a recurrence with 64% of those being within 30 days of the initial infection [[#References|[2]]]. Complications typically develop in about 11% of patients in the first recurrence. This likely promotes the growth of antibiotic resistant strains that are able to perform horizontal gene transfer between recurrences. In about 20% of patients the infection will resolve itself in 2-3 of discontinuing the inciting antibiotic. Most infections that persist are treated with a 10-14 day course of antibiotics like metronidazole, vancomycin, and rehydration therapy. In more serious cases fecal transplants and surgery can be performed. [[#References|[3]]] Patients at risk for developing CDAD include those taking antibiotics (especially broad spectrum), those taking proton pump inhibitors, GI manipulation or surgery, long term stays in hospital or clinical settings, immunocompromising conditions, and old age. The best practices for preventing infection include judicious administration of antibiotics, quarantine, hand hygiene, and the use of EPA-registered disinfectants with a sporicide (especially hypochlorite based disinfectants).<br />
<br />
==Pathogenesis==<br />
[[File:Clostridium difficile pathogenesis.jpeg|500px|thumb|right|Pathogenesis of <i>Clostridium difficile</i> and formation of pseudomembranes. From: Nature.com [http://www.nature.com/nrmicro/journal/v7/n7/fig_tab/nrmicro2164_F5.html]]]<br />
<br />
===Transmission===<br />
<i>Clostridium difficile</i> are shed in feces, and therefore this bacteria can be transmitted via the fecal-oral route. The spores can survive on almost any surface for months to years which makes the pathogen very difficult to get rid of once established. The spores are resistant to many extreme environments, including high temperatures, ultraviolet light, harsh chemicals, and antibiotics. Health care settings, including patients and workers, are often the reservoirs for <i>C. difficile</i> spores. Community-acquired infections are thought to be transmitted through soil, water, pets, meats, and vegetables.<br />
<br />
===Infectious dose, incubation, and colonization===<br />
Since <i>C. difficile</i> is an opportunistic pathogen, the infectious dose and incubation period is unknown and widely debated. Exposure to broad spectrum antibiotics prior to infection is crucial to the pathogenesis, as <i>C. difficile</i> has a difficult time colonizing on its own, but it can be found as part of the normal gut microbiota of approximately 2-3% of the population. Once a patient has taken broad-spectrum antibiotics, <i>C. difficile</i> takes advantage of the lack of commensal bacteria in order to colonize the large intestine.<br />
<br />
===Epidemiology===<br />
====Frequency====<br />
CDAD is most often a hospital-acquired infection that causes an estimated 3 million cases of diarrhea and colitis per year. Some reports state that 28% of patients who were hospitalized tested positive for <i>C. difficile</i>. Its incidence in hospitals has risen from 30-40 per 100,000 in the 1990s to 84 per 100,000 in 2005 [[#References|[4]]], and despite a decrease in other nosocomial infections from 2000-2009, the number of patients with CDAD discharge diagnosis more than doubled from approximately 139,000 to 336,600. In addition to this, the number of primary CDAD diagnoses more than tripled from 33,000 to 111,000. CDAD can be community-acquired, however the incidence of this is much lower than the hospital-acquired infections. The CDC’s Emerging Infections Program associated approximately 94% of CDAD diagnoses with receiving health care. Outside of the United States, the incidence of CDAD has also increased. For example, in one region of Quebec, its incidence quadrupled in 2003 to 92.2 per 100,000 populations.<br />
<br />
====Morbidity and Mortality====<br />
Though most patients with <i>C. difficile</i> can recover without specific therapy, symptoms may be particularly debilitating and drawn out. The elderly are much more susceptible to severe infection, and the mortality rate in this demographic is estimated to be as high as 25%. The disease’s mortality and morbidity seems to have increased in severity in the last decade. The CDC has reported that enteritis deaths more than doubled from 1997 to 2007 in the United States, increasing to 17,000 from about 7,000, and C difficile was associated with 14,500 of these deaths, up from 2,700 in 1999 [[#References|[5]]]. A particularly virulent strain has been traced to several outbreaks in North America, known as the NAP1/027 strain. It shows increased production of toxins A and B, antibiotic resistance, and the production of a binary toxin whose role is not yet clear, but is thought to increase the virulence of the A and B toxins.<br />
<br />
===Virulence factors===<br />
<i>C. difficile</i> expresses two toxins, toxin A (TcdA) and toxin B (TcdB), which are two of the largest bacterial toxins known (review). They are part of the Large Clostridial Toxin family, in which the toxins glucosylate small GTPases in the cytosol of targeted cells. Both toxins disrupt the actin cytoskeleton of fibroblasts and prevent cells from being able to regulate actin polymerization. Toxin A produces a florid inflammatory response, while B has no enterotoxin activity, but instead is a potent cytotoxin. In fact, toxin B is 10 times more potent than A in causing damage in colonic epithelial cells, which points to toxin B as the primary virulence factor. The primary virulence factor for this bacteria has been disputed. It was previously thought to be toxin A, but recent evidence points towards toxin B.<br />
<br />
==Clinical features==<br />
<br />
Colonization of the intestine by <i>Clostridium difficile</i> can occur without presenting any symptoms in the host, however, infection can cause symptoms ranging from trivial diarrhea to serious manifestations of disease. General symptoms of CDAD include watery diarrhea, fever, loss of appetite, nausea, and abdominal pain/tenderness, but grossly bloody stools are unusual. Signs of more advanced disease include pseudomembranous colitis, toxic megacolon (also known as colonic distention), perforations of the colon, sepsis, and sometimes death. <br><br><br />
One of the most well recognized manifestations of the disease, pseudomembranous colitis, was first described in 1893 and is the formation of lesions within the colon that are made of a pseudomembrane of immune cells, mucus, and necrotic tissue [[#References|[4]]]. For 20% of patients with advanced CDAD: diarrhea and fluid loss are minimal, and instead, abdominal distention and bowel obstruction can lead to misdiagnosis. For other patients, signs of systemic toxicity and systemic inflammatory syndrome, including leukocytosis, rising serum lactate levels, hypotension, acute renal failure, and respiratory distress, lead to poor prognosis and high mortality rates. Fulminant colitis can lead to the need for a total colectomy, but even with this procedure, the average mortality rate at this stage of the disease is 67%, and the progression from initial symptoms to this stage can occur in as little as hours to as much as weeks.<br />
<br />
==Diagnosis==<br />
<br />
Prior to testing for <i>Clostridium difficile</i>, there are three predominate indications for the presumption of a <i>C. difficile</i> infection (CDI). Patients are most susceptible if they have received antibiotics within the last 8-12 weeks; patients are over the age of 64; patients have produced 3 or more diarrheal stools within 24 hours. The most widely accepted method used to test for CDI is a toxigenic culture involving the incubation of a fecal culture and subsequent immunoassay to test for the presence of <i>C. difficile</i> toxin A [[#References|[6,7]]]. <br />
PCR is becoming a more popular method to identify toxins A and B because of its specificity, sensitivity, and rapid results. However, physicians warn that false positives are easily obtained from asymptomatic individuals. For this reason, physicians and researchers direct only to test diarrheal stool, especially from individuals who identify with any of the three preliminary traits listed above [[#References|[6]]].<br />
<br />
The application of a two-step technique involving an enzyme immunoassay (EIA) and a confirmatory step to detect the presence of <i>C. difficile</i> toxins in stool samples has also proven effective in clinical laboratories. The EIA is used to detect glutamate dehydrogenase (GDH); positive samples are then subject to toxigenic culturing. However, this method still requires further confirmation to determine the relative sensitivity and consistency among GDH test kits ([[#References|[6,7]]].<br />
<br />
In comparison to the EIA technique, the tissue cytotoxin assay shows higher specificity for toxin detection, but is a more complex and time intensive procedure. Tissue cytotoxin assays are considered inefficient in clinical settings [[#References|[6]]].<br />
<br />
Repeat testing from a single stool sample is not encouraged due to the increased risk for false-positive results [[#References|[6,7]]]. Additionally, retesting a recently recovered patient may produce misleading results since <i>C. difficile</i> likely remains colonized for a period of time after CDI symptoms subside [[#References|[6]]].<br />
<br />
==Treatment==<br />
<br />
===Non-severe cases===<br />
For non-severe cases, the first step in treatment is the cessation of the inciting antibiotic as soon as possible and only continuing concomitant antibiotics if they are prudent to the treatment of the initial infection. Oral metronidazole or vancomycin are typically administered. However, some literature points to vancomycin having increased efficacy over metronidazole [[#References|[8]]].<br />
<br />
===Moderate to severe cases===<br />
<b>Antibiotics:</b><br><br />
For more severe cases, higher, more frequent doses of vancomycin (either oral or rectal) are administered. However, rectal doses have a higher risk of producing colonic perforations and should only be administered when oral preparations are impossible for the patient.<br />
<br><br><br />
<b>Fecal Transplantation:</b><br><br />
Another method of treatment is the infusion of a purified stool substitute preparation from a healthy donor. Generally, fecal transplantation is used in cases where the patient has had multiple recurrent infections and both metronidazole and vancomycin fail. It is reasonably successful in repopulating the gut with commensal bacteria and combating antibiotic resistant CDAD [[#References|[9]]].<br />
<br><br><br />
<b>Probiotics:</b><br><br />
Antibiotics function to alter the intestinal flora in order to produce an unfavorable environment for <i>C. difficile</i>. Some Lactobacilli, in particular, <i>S. boulardii,</i> have been shown to suppress <i>C. difficile</i> growth in hamsters. Furthermore, temporarily populating the gut with particular Lactobacilli can lower the pH of the surrounding environment and secrete degradation enzymes like proteases that place stress on the <i>C. difficile</i> population. Finally, some strains of beneficial bacteria may have the ability to protect the intestinal barrier by interfering TcdA and TcdB binding to the host gut epithelium [[#References|[10]]].<br />
<br><br><br />
<b>Immunomodulation:</b><br><br />
New research suggests that the supplementation of laboratory-derived monoclonal antibodies may have the ability to inhibit <i>C. difficile</i> colonization by stimulating toll-like receptors and upregulating expression of dendritic cells and peripheral blood monocytes [[#References|[11]]].<br />
<br><br><br />
<b>Surgery:</b><br><br />
Some severely ill patients with CDAD may require surgical intervention as a result of toxic megacolon, colonic perforations, necrotizing colitis, or infections producing systemic inflammatory responses that could potentially lead to organ failure. In these cases, diseased portions of the gastrointestinal tract are removed.<br />
<br />
==Prevention==<br />
Prevention with good hygiene habits will go a long way to protect against opportunistic pathogens like C. difficile. The main focus with C. difficile specifically should be on more conscientious antibiotic use, as broad spectrum antibiotics make patients susceptible in the first place. Restricting antibiotic use should lower the incidence of the disease and hopefully slow its growing virulence. When dealing with CDAD patients in a hospital setting, isolation of the sick, proper hand washing techniques, protective gowns and gloves, and cleaning with sodium hypochlorite are all important and effective ways to prevent outbreaks in healthcare settings. Work on a vaccine has begun, which appears to be promising, but is still far from market availability.<br />
<br />
==Host Immune Response==<br />
The pathophysiology of <i>C. difficile</i> is directly related to the host immune response to CDI. <i>C. difficile</i> colonizes in the lumen of the small intestine where it can lie dormant by means of sporulation, or it produces enterotoxins TcdA and TcdB, eliciting an inflammatory immune response. Toxin A attracts polymorphonuclear cells (PMNs) or neutrophils to the site of infection via cytokines from epithelial host cells. This influx of leukocytes as a function of the immune response increases vascular permeability, allowing TcdA and TcdB to cross the mucosal membrane. TcdB degrades colonic epithelial cells. Accumulations of leukocytes form a pseudomembrane on the lining of the colon (pseudomembranous colitis).<br><br><br />
<br />
Current research suggests that upon exposure to <i>C. difficile</i>, humans develop an adaptive immunity to TcdA and TcdB. It is estimated that approximately 60% of healthy adults exhibit IgG and IgA antibodies against C. difficile toxins. Studies suggest that adaptive immunity can begin in childhood from environmental exposure to <i>C. difficile</i>, and possibly non-toxigenic clostridial species [[#References|[13,14]]]. Studies show that immunoglobulin A (IgA) antibody inhibits TcdA binding to epithelial cells in the colon [[#References|[12]]]. Moreover, higher levels of IgA and IgG anti-toxins were found in asymptomatic patients, as well as those who displayed minor symptoms of CDAD [[#References|[13,14]]].<br />
<br />
==References==<br />
<br />
1. Larson HE, Price AB, Honour P, Borriello SP: <i>Clostridium difficile</i> and the aetiology of pseudomembranous colitis. <i>Lancet</i> 1978, 1: 1063-1066. <br><br />
2. Pepin J, Alary ME, Valiquette L, Raiche E, Ruel J, Godin D, Bourassa C: Increasing risk of relapse after treatment of <i>Clostridium difficile</i> colitis in Quebec, Canada. <i>Clin Infect Dis</i>. 2005 Jun 1; 40(11): 1591-7.<br><br />
3. LaMont JT, Calderwood SB, et al.: <i>Clostridium difficile</i> in adults: Clinical manifestations and diagnosis. UpToDate June 2013, Available at: http://www.uptodate.com/contents/clostridium-difficile-in-adults-clinical-manifestations-and-diagnosis.<br><br />
4. CDC. Vital Signs: Preventing Clostridium difficile Infections. <i>MMWR Morb Mortal Wkly Rep</i>. Mar 9 2012;61:157-62. [Medline].<br><br />
5. Centers for Disease Control and Prevention (CDC). Deaths from gastroenteritis double. Available at http://www.cdc.gov/media/releases/2012/p0314_gastroenteritis.html.<br><br />
6. Gould, Carolyn. CDC Commentary: Testing for <i>Clostridium difficile</i> Infection. <i>Medscape</i>. Aug 16, 2010.<br><br />
7. Cohen S., Gerding D., Johnson S., Kelly C., Loo V., McDonald L., Pepin J., Wilcox M. (2010). Clinical Practice Guidelines for <i>Clostridium difficile</i> Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America. <i>Infection Control and Hospital Epidemiology</i> 31(5):431-455. <br><br />
8. Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to <i>Clostridium difficile</i>. Gut 1986; 27: 1169.<br><br />
9. Petrof EO, Gloor GB, Vanner SJ et al. Stool substitute transplant therapy for the eradication of <i>Clostridium difficile</i> infection: ‘RePOOPulating’ the gut. <i>Microbiome</i> 2013 January; 1:3<br><br />
10. Sartor RB, LaMont JT, Probiotics for gastrointestinal diseases. UpToDate June 2013, Available at: http://www.uptodate.com/contents/probiotics-for-gastrointestinal-diseases?source=see_link&anchor=H7#H7<br><br />
11. Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against <i>Clostridium difficile</i> toxins. N Engl J Med 2010; 362:197.<br><br />
12. Kelly C. P., Pothoulakis C., Orellana J., Lamont J.T. (1992). Human colonic aspirates containing immunoglobulin A antibody to <i>Clostridium difficile</i> toxin A inhibit toxin A-receptor binding. <i>Gastroenterology</i> 102, 35-40. Pmid:1309359.<br />
<br><br />
13. Kyne L., Warny M., Qamar A., Kelly C.P. (2000). Asymptomatic carriage of <i>Clostridium difficile</i> and serum levels of IgG antibody against toxin A. <i>N Engl J Med</i> 342, 390-397. <br />
<br><br />
14. Viscidi R, Laughon BE, Yolken R, et al. Serum antibody response to toxins A and B of <i>Clostridium<br />
difficile</i>. J Infect Dis 1983;148:93–100. [PubMed: 6886489]<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Laura Boucher, Marrett Hild, and Lillian Flannigan, students of Tyrrell Conway at the University of Oklahoma</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Clostridium_difficile-associated_disease&diff=90946Clostridium difficile-associated disease2013-07-23T12:27:17Z<p>Halen.M.Borron-1: /* Virulence factors */</p>
<hr />
<div>{{Curated}}<br />
[[Image:OULOGOBIANCO.JPEG|thumb|230px|left|University of Oklahoma Study Abroad Microbiology in Arezzo, Italy[http://cas.ou.edu/study-abroad/]]]<br />
[[File:Clostridium difficile spore.gif|400px|thumb|right|Scanning electron microscope image of <i>Clostridium difficile</i>. From: Bioquell.com [http://www.bioquell.com/technology/microbiology/clostridium-difficile/]]]<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Firmicutes]]<br />
| Class = [[Clostridia]]<br />
| Order = [[Clostridiales]]<br />
| Family = [[Clostridiaceae]]<br />
| Genus = [[Clostridium]]<br />
| species = [[Clostridium difficile]]<br />
<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=1496&lvl=3&lin=f&keep=1&srchmode=1&unlock Taxonomy] Genome: <font size="2">[http://www.ncbi.nlm.nih.gov/genome/?term=clostridium+difficile Genome]</font>'''<br />
|}<br />
<br />
===Description===<br />
<i>Clostridium difficile</i> causes pseudomembranous colitis, toxic megacolon, perforations of the colon, sepsis, and, on occasion, death. It is a Gram-positive, spore-forming rod that is an obligate anaerobe. It can be found in soil, water, feces, and the human gut. <i>C. difficile</i> is a normal inhabitant of the gut microbial community of about 1-3% of adults. The pathogenic form of <i>C. difficile</i> is transferred via the fecal-oral route as well as through spore dispersal. <i>Clostridium difficile</i>-associated disease (CDAD) was initially reported approximately 30 years ago. The CDC first recorded infections from a hyper-virulent strain in 2000 along with a marked increase in the number of CDAD infections. <i>C. difficile</i> causes disease by producing the toxins TcdA and TcdB that function to disrupt protein synthesis within the host cell. The toxins are responsible for producing symptoms such as watery diarrhea, fever, loss of appetite, nausea, and severe abdominal pain [[#References|[1]]]. Although <i>C. difficile</i> only causes about 20% of antibiotic associated colitis, standard treatments fail in about 25% of CDAD cases. Patients treated promptly typically recover. However, CDAD is notorious for recurrence after initial antibiotic treatment. 33% of patients with an infection will have a recurrence with 64% of those being within 30 days of the initial infection [[#References|[2]]]. Complications typically develop in about 11% of patients in the first recurrence. This likely promotes the growth of antibiotic resistant strains that are able to perform horizontal gene transfer between recurrences. In about 20% of patients the infection will resolve itself in 2-3 of discontinuing the inciting antibiotic. Most infections that persist are treated with a 10-14 day course of antibiotics like metronidazole, vancomycin, and rehydration therapy. In more serious cases fecal transplants and surgery can be performed. [[#References|[3]]] Patients at risk for developing CDAD include those taking antibiotics (especially broad spectrum), those taking proton pump inhibitors, GI manipulation or surgery, long term stays in hospital or clinical settings, immunocompromising conditions, and old age. The best practices for preventing infection include judicious administration of antibiotics, quarantine, hand hygiene, and the use of EPA-registered disinfectants with a sporicide (especially hypochlorite based disinfectants).<br />
<br />
==Pathogenesis==<br />
[[File:Clostridium difficile pathogenesis.jpeg|500px|thumb|right|Pathogenesis of <i>Clostridium difficile</i> and formation of pseudomembranes. From: Nature.com [http://www.nature.com/nrmicro/journal/v7/n7/fig_tab/nrmicro2164_F5.html]]]<br />
<br />
===Transmission===<br />
<i>Clostridium difficile</i> are shed in feces, and therefore this bacteria can be transmitted via the fecal-oral route. The spores can survive on almost any surface for months to years which makes the pathogen very difficult to get rid of once established. The spores are resistant to many extreme environments, including high temperatures, ultraviolet light, harsh chemicals, and antibiotics. Health care settings, including patients and workers, are often the reservoirs for <i>C. difficile</i> spores. Community-acquired infections are thought to be transmitted through soil, water, pets, meats, and vegetables.<br />
<br />
===Infectious dose, incubation, and colonization===<br />
Since <i>C. difficile</i> is an opportunistic pathogen, the infectious dose and incubation period is unknown and widely debated. Exposure to broad spectrum antibiotics prior to infection is crucial to the pathogenesis, as <i>C. difficile</i> has a difficult time colonizing on its own, but it can be found as part of the normal gut microbiota of approximately 2-3% of the population. Once a patient has taken broad-spectrum antibiotics, <i>C. difficile</i> takes advantage of the lack of commensal bacteria in order to colonize the large intestine.<br />
<br />
===Epidemiology===<br />
====Frequency====<br />
CDAD is most often a hospital-acquired infection that causes an estimated 3 million cases of diarrhea and colitis per year. Some reports state that 28% of patients who were hospitalized tested positive for <i>C. difficile</i>. Its incidence in hospitals has risen from 30-40 per 100,000 in the 1990s to 84 per 100,000 in 2005 [[#References|[4]]], and despite a decrease in other nosocomial infections from 2000-2009, the number of patients with CDAD discharge diagnosis more than doubled from approximately 139,000 to 336,600. In addition to this, the number of primary CDAD diagnoses more than tripled from 33,000 to 111,000. CDAD can be community-acquired, however the incidence of this is much lower than the hospital-acquired infections. The CDC’s Emerging Infections Program associated approximately 94% of CDAD diagnoses with receiving health care. Outside of the United States, the incidence of CDAD has also increased. For example, in one region of Quebec, its incidence quadrupled in 2003 to 92.2 per 100,000 populations.<br />
<br />
====Morbidity and Mortality====<br />
Though most patients with <i>C. difficile</i> can recover without specific therapy, symptoms may be particularly debilitating and drawn out. The elderly are much more susceptible to severe infection, and the mortality rate in this demographic is estimated to be as high as 25%. The disease’s mortality and morbidity seems to have increased in severity in the last decade. The CDC has reported that enteritis deaths more than doubled from 1997 to 2007 in the United States, increasing to 17,000 from about 7,000, and C difficile was associated with 14,500 of these deaths, up from 2,700 in 1999 [[#References|[5]]]. A particularly virulent strain has been traced to several outbreaks in North America, known as the NAP1/027 strain. It shows increased production of toxins A and B, antibiotic resistance, and the production of a binary toxin whose role is not yet clear, but is thought to increase the virulence of the A and B toxins.<br />
<br />
===Virulence factors===<br />
<i>C. difficile</i> expresses two toxins, toxin A (TcdA) and toxin B (TcdB), which are two of the largest bacterial toxins known (review). They are part of the Large Clostridial Toxin family, in which the toxins glucosylate small GTPases in the cytosol of targeted cells. Both toxins disrupt the actin cytoskeleton of fibroblasts and prevent cells from being able to regulate actin polymerization. Toxin A produces a florid inflammatory response, while B has no enterotoxin activity, but instead is a potent cytotoxin. In fact, toxin B is 10 times more potent than A in causing damage in colonic epithelial cells, which points to toxin B as the primary virulence factor. The primary virulence factor for this bacteria has been disputed. It was previously thought to be toxin A, but recent evidence points towards toxin B.<br />
<br />
==Clinical features==<br />
<br />
Colonization of the intestine by <i>Clostridium difficile</i> can occur without presenting any symptoms in the host, however, infection can cause symptoms ranging from trivial diarrhea to serious manifestations of disease. General symptoms of CDAD include watery diarrhea, fever, loss of appetite, nausea, and abdominal pain/tenderness, but grossly bloody stools are unusual. Signs of more advanced disease include pseudomembranous colitis, toxic megacolon (also known as colonic distention), perforations of the colon, sepsis, and sometimes death. <br><br><br />
One of the most well recognized manifestations of the disease, pseudomembranous colitis, was first described in 1893 and is the formation of lesions within the colon that are made of a pseudomembrane of immune cells, mucus, and necrotic tissue [[#References|[4]]]. For 20% of patients with advanced CDAD: diarrhea and fluid loss are minimal, and instead, abdominal distention and bowel obstruction can lead to misdiagnosis. For other patients, signs of systemic toxicity and systemic inflammatory syndrome, including leukocytosis, rising serum lactate levels, hypotension, acute renal failure, and respiratory distress, lead to poor prognosis and high mortality rates. Fulminant colitis can lead to the need for a total colectomy, but even with this procedure, the average mortality rate at this stage of the disease is 67%, and the progression from initial symptoms to this stage can occur in as little as hours to as much as weeks.<br />
<br />
==Diagnosis==<br />
<br />
Prior to testing for <i>Clostridium difficile</i>, there are three predominate indications for the presumption of a <i>C. difficile</i> infection (CDI). Patients are most susceptible if they have received antibiotics within the last 8-12 weeks; patients are over the age of 64; patients have produced 3 or more diarrheal stools within 24 hours. The most widely accepted method used to test for CDI is a toxigenic culture involving the incubation of a fecal culture and subsequent immunoassay to test for the presence of <i>C. difficile</i> toxin A [[#References|[6,7]]]. <br />
PCR is becoming a more popular method to identify toxins A and B because of its specificity, sensitivity, and rapid results. However, physicians warn that false positives are easily obtained from asymptomatic individuals. For this reason, physicians and researchers direct only to test diarrheal stool, especially from individuals who identify with any of the three preliminary traits listed above [[#References|[6]]].<br />
<br />
The application of a two-step technique involving an enzyme immunoassay (EIA) and a confirmatory step to detect the presence of <i>C. difficile</i> toxins in stool samples has also proven effective in clinical laboratories. The EIA is used to detect glutamate dehydrogenase (GDH); positive samples are then subject to toxigenic culturing. However, this method still requires further confirmation to determine the relative sensitivity and consistency among GDH test kits ([[#References|[6,7]]].<br />
<br />
In comparison to the EIA technique, the tissue cytotoxin assay shows higher specificity for toxin detection, but is a more complex and time intensive procedure. Tissue cytotoxin assays are considered inefficient in clinical settings [[#References|[6]]].<br />
<br />
Repeat testing from a single stool sample is not encouraged due to the increased risk for false-positive results [[#References|[6,7]]]. Additionally, retesting a recently recovered patient may produce misleading results since <i>C. difficile</i> likely remains colonized for a period of time after CDI symptoms subside [[#References|[6]]].<br />
<br />
==Treatment==<br />
<br />
===Non-severe cases===<br />
For non-severe cases, the first step in treatment is the cessation of the inciting antibiotic as soon as possible and only continuing concomitant antibiotics if they are prudent to the treatment of the initial infection. Oral metronidazole or vancomycin are typically administered. However, some literature points to vancomycin having increased efficacy over metronidazole [[#References|[8]]].<br />
<br />
===Moderate to severe cases===<br />
<b>Antibiotics:</b><br><br />
For more severe cases higher, more frequent doses of vancomycin (either oral or rectal) are administered. However, rectal doses have a higher risk of producing colonic perforations and should only be administered when oral preparations are impossible for the patient.<br />
<br><br><br />
<b>Fecal Transplantation:</b><br><br />
Another method of treatment is the infusion of a purified stool substitute preparation from a healthy donor. Generally, fecal transplantation is used in cases where the patient has had multiple recurrent infections and both metronidazole and vancomycin fail. It is reasonably successful in repopulating the gut with commensal bacteria and combating antibiotic resistant CDAD [[#References|[9]]].<br />
<br><br><br />
<b>Probiotics:</b><br><br />
Antibiotics function to alter the intestinal flora in order to produce an unfavorable environment for <i>C. difficile</i>. Some Lactobacilli, in particular, <i>S. boulardii,</i> have been shown to suppress <i>C. difficile</i> growth in hamsters. Furthermore, temporarily populating the gut with particular Lactobacilli can lower the pH of the surrounding environment and secrete degradation enzymes like proteases that place stress on the <i>C. difficile</i> population. Finally, some strains of beneficial bacteria may have the ability to protect the intestinal barrier by interfering TcdA and TcdB binding to the host gut epithelium [[#References|[10]]].<br />
<br><br><br />
<b>Immunomodulation:</b><br><br />
New research suggests that the supplementation of laboratory-derived monoclonal antibodies may have the ability to inhibit <i>C. difficile</i> colonization by stimulating toll-like receptors and upregulating expression of dendritic cells and peripheral blood monocytes [[#References|[11]]].<br />
<br><br><br />
<b>Surgery:</b><br><br />
Some severely ill patients with CDAD may require surgical intervention as a result of toxic megacolon, colonic perforations, necrotizing colitis, or infections producing systemic inflammatory responses that could potentially lead to organ failure. In these cases, diseased portions of the gastrointestinal tract are removed.<br />
<br />
==Prevention==<br />
Prevention with good hygiene habits will go a long way to protect against opportunistic pathogens like C. difficile. The main focus with C. difficile specifically should be on more conscientious antibiotic use, as broad spectrum antibiotics make patients susceptible in the first place. Restricting antibiotic use should lower the incidence of the disease and hopefully slow its growing virulence. When dealing with CDAD patients in a hospital setting, isolation of the sick, proper hand washing techniques, protective gowns and gloves, and cleaning with sodium hypochlorite are all important and effective ways to prevent outbreaks in healthcare settings. Work on a vaccine has begun, which appears to be promising, but is still far from market availability.<br />
<br />
==Host Immune Response==<br />
The pathophysiology of <i>C. difficile</i> is directly related to the host immune response to CDI. <i>C. difficile</i> colonizes in the lumen of the small intestine where it can lie dormant by means of sporulation, or it produces enterotoxins TcdA and TcdB, eliciting an inflammatory immune response. Toxin A attracts polymorphonuclear cells (PMNs) or neutrophils to the site of infection via cytokines from epithelial host cells. This influx of leukocytes as a function of the immune response increases vascular permeability, allowing TcdA and TcdB to cross the mucosal membrane. TcdB degrades colonic epithelial cells. Accumulations of leukocytes form a pseudomembrane on the lining of the colon (pseudomembranous colitis).<br><br><br />
<br />
Current research suggests that upon exposure to <i>C. difficile</i>, humans develop an adaptive immunity to TcdA and TcdB. It is estimated that approximately 60% of healthy adults exhibit IgG and IgA antibodies against C. difficile toxins. Studies suggest that adaptive immunity can begin in childhood from environmental exposure to <i>C. difficile</i>, and possibly non-toxigenic clostridial species [[#References|[13,14]]]. Studies show that immunoglobulin A (IgA) antibody inhibits TcdA binding to epithelial cells in the colon [[#References|[12]]]. Moreover, higher levels of IgA and IgG anti-toxins were found in asymptomatic patients, as well as those who displayed minor symptoms of CDAD [[#References|[13,14]]].<br />
<br />
==References==<br />
<br />
1. Larson HE, Price AB, Honour P, Borriello SP: <i>Clostridium difficile</i> and the aetiology of pseudomembranous colitis. <i>Lancet</i> 1978, 1: 1063-1066. <br><br />
2. Pepin J, Alary ME, Valiquette L, Raiche E, Ruel J, Godin D, Bourassa C: Increasing risk of relapse after treatment of <i>Clostridium difficile</i> colitis in Quebec, Canada. <i>Clin Infect Dis</i>. 2005 Jun 1; 40(11): 1591-7.<br><br />
3. LaMont JT, Calderwood SB, et al.: <i>Clostridium difficile</i> in adults: Clinical manifestations and diagnosis. UpToDate June 2013, Available at: http://www.uptodate.com/contents/clostridium-difficile-in-adults-clinical-manifestations-and-diagnosis.<br><br />
4. CDC. Vital Signs: Preventing Clostridium difficile Infections. <i>MMWR Morb Mortal Wkly Rep</i>. Mar 9 2012;61:157-62. [Medline].<br><br />
5. Centers for Disease Control and Prevention (CDC). Deaths from gastroenteritis double. Available at http://www.cdc.gov/media/releases/2012/p0314_gastroenteritis.html.<br><br />
6. Gould, Carolyn. CDC Commentary: Testing for <i>Clostridium difficile</i> Infection. <i>Medscape</i>. Aug 16, 2010.<br><br />
7. Cohen S., Gerding D., Johnson S., Kelly C., Loo V., McDonald L., Pepin J., Wilcox M. (2010). Clinical Practice Guidelines for <i>Clostridium difficile</i> Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America. <i>Infection Control and Hospital Epidemiology</i> 31(5):431-455. <br><br />
8. Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to <i>Clostridium difficile</i>. Gut 1986; 27: 1169.<br><br />
9. Petrof EO, Gloor GB, Vanner SJ et al. Stool substitute transplant therapy for the eradication of <i>Clostridium difficile</i> infection: ‘RePOOPulating’ the gut. <i>Microbiome</i> 2013 January; 1:3<br><br />
10. Sartor RB, LaMont JT, Probiotics for gastrointestinal diseases. UpToDate June 2013, Available at: http://www.uptodate.com/contents/probiotics-for-gastrointestinal-diseases?source=see_link&anchor=H7#H7<br><br />
11. Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against <i>Clostridium difficile</i> toxins. N Engl J Med 2010; 362:197.<br><br />
12. Kelly C. P., Pothoulakis C., Orellana J., Lamont J.T. (1992). Human colonic aspirates containing immunoglobulin A antibody to <i>Clostridium difficile</i> toxin A inhibit toxin A-receptor binding. <i>Gastroenterology</i> 102, 35-40. Pmid:1309359.<br />
<br><br />
13. Kyne L., Warny M., Qamar A., Kelly C.P. (2000). Asymptomatic carriage of <i>Clostridium difficile</i> and serum levels of IgG antibody against toxin A. <i>N Engl J Med</i> 342, 390-397. <br />
<br><br />
14. Viscidi R, Laughon BE, Yolken R, et al. Serum antibody response to toxins A and B of <i>Clostridium<br />
difficile</i>. J Infect Dis 1983;148:93–100. [PubMed: 6886489]<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
<br />
Created by Laura Boucher, Marrett Hild, and Lillian Flannigan, students of Tyrrell Conway at the University of Oklahoma</div>Halen.M.Borron-1https://microbewiki.kenyon.edu/index.php?title=Clostridium_difficile-associated_disease&diff=90945Clostridium difficile-associated disease2013-07-23T12:25:50Z<p>Halen.M.Borron-1: /* Virulence factors */</p>
<hr />
<div>{{Curated}}<br />
[[Image:OULOGOBIANCO.JPEG|thumb|230px|left|University of Oklahoma Study Abroad Microbiology in Arezzo, Italy[http://cas.ou.edu/study-abroad/]]]<br />
[[File:Clostridium difficile spore.gif|400px|thumb|right|Scanning electron microscope image of <i>Clostridium difficile</i>. From: Bioquell.com [http://www.bioquell.com/technology/microbiology/clostridium-difficile/]]]<br />
==Etiology/Bacteriology==<br />
===Taxonomy===<br />
| Domain = [[Bacteria]]<br />
| Phylum = [[Firmicutes]]<br />
| Class = [[Clostridia]]<br />
| Order = [[Clostridiales]]<br />
| Family = [[Clostridiaceae]]<br />
| Genus = [[Clostridium]]<br />
| species = [[Clostridium difficile]]<br />
<br />
{|<br />
| height="10" bgcolor="#FFDF95" |<br />
'''NCBI: [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=1496&lvl=3&lin=f&keep=1&srchmode=1&unlock Taxonomy] Genome: <font size="2">[http://www.ncbi.nlm.nih.gov/genome/?term=clostridium+difficile Genome]</font>'''<br />
|}<br />
<br />
===Description===<br />
<i>Clostridium difficile</i> causes pseudomembranous colitis, toxic megacolon, perforations of the colon, sepsis, and, on occasion, death. It is a Gram-positive, spore-forming rod that is an obligate anaerobe. It can be found in soil, water, feces, and the human gut. <i>C. difficile</i> is a normal inhabitant of the gut microbial community of about 1-3% of adults. The pathogenic form of <i>C. difficile</i> is transferred via the fecal-oral route as well as through spore dispersal. <i>Clostridium difficile</i>-associated disease (CDAD) was initially reported approximately 30 years ago. The CDC first recorded infections from a hyper-virulent strain in 2000 along with a marked increase in the number of CDAD infections. <i>C. difficile</i> causes disease by producing the toxins TcdA and TcdB that function to disrupt protein synthesis within the host cell. The toxins are responsible for producing symptoms such as watery diarrhea, fever, loss of appetite, nausea, and severe abdominal pain [[#References|[1]]]. Although <i>C. difficile</i> only causes about 20% of antibiotic associated colitis, standard treatments fail in about 25% of CDAD cases. Patients treated promptly typically recover. However, CDAD is notorious for recurrence after initial antibiotic treatment. 33% of patients with an infection will have a recurrence with 64% of those being within 30 days of the initial infection [[#References|[2]]]. Complications typically develop in about 11% of patients in the first recurrence. This likely promotes the growth of antibiotic resistant strains that are able to perform horizontal gene transfer between recurrences. In about 20% of patients the infection will resolve itself in 2-3 of discontinuing the inciting antibiotic. Most infections that persist are treated with a 10-14 day course of antibiotics like metronidazole, vancomycin, and rehydration therapy. In more serious cases fecal transplants and surgery can be performed. [[#References|[3]]] Patients at risk for developing CDAD include those taking antibiotics (especially broad spectrum), those taking proton pump inhibitors, GI manipulation or surgery, long term stays in hospital or clinical settings, immunocompromising conditions, and old age. The best practices for preventing infection include judicious administration of antibiotics, quarantine, hand hygiene, and the use of EPA-registered disinfectants with a sporicide (especially hypochlorite based disinfectants).<br />
<br />
==Pathogenesis==<br />
[[File:Clostridium difficile pathogenesis.jpeg|500px|thumb|right|Pathogenesis of <i>Clostridium difficile</i> and formation of pseudomembranes. From: Nature.com [http://www.nature.com/nrmicro/journal/v7/n7/fig_tab/nrmicro2164_F5.html]]]<br />
<br />
===Transmission===<br />
<i>Clostridium difficile</i> are shed in feces, and therefore this bacteria can be transmitted via the fecal-oral route. The spores can survive on almost any surface for months to years which makes the pathogen very difficult to get rid of once established. The spores are resistant to many extreme environments, including high temperatures, ultraviolet light, harsh chemicals, and antibiotics. Health care settings, including patients and workers, are often the reservoirs for <i>C. difficile</i> spores. Community-acquired infections are thought to be transmitted through soil, water, pets, meats, and vegetables.<br />
<br />
===Infectious dose, incubation, and colonization===<br />
Since <i>C. difficile</i> is an opportunistic pathogen, the infectious dose and incubation period is unknown and widely debated. Exposure to broad spectrum antibiotics prior to infection is crucial to the pathogenesis, as <i>C. difficile</i> has a difficult time colonizing on its own, but it can be found as part of the normal gut microbiota of approximately 2-3% of the population. Once a patient has taken broad-spectrum antibiotics, <i>C. difficile</i> takes advantage of the lack of commensal bacteria in order to colonize the large intestine.<br />
<br />
===Epidemiology===<br />
====Frequency====<br />
CDAD is most often a hospital-acquired infection that causes an estimated 3 million cases of diarrhea and colitis per year. Some reports state that 28% of patients who were hospitalized tested positive for <i>C. difficile</i>. Its incidence in hospitals has risen from 30-40 per 100,000 in the 1990s to 84 per 100,000 in 2005 [[#References|[4]]], and despite a decrease in other nosocomial infections from 2000-2009, the number of patients with CDAD discharge diagnosis more than doubled from approximately 139,000 to 336,600. In addition to this, the number of primary CDAD diagnoses more than tripled from 33,000 to 111,000. CDAD can be community-acquired, however the incidence of this is much lower than the hospital-acquired infections. The CDC’s Emerging Infections Program associated approximately 94% of CDAD diagnoses with receiving health care. Outside of the United States, the incidence of CDAD has also increased. For example, in one region of Quebec, its incidence quadrupled in 2003 to 92.2 per 100,000 populations.<br />
<br />
====Morbidity and Mortality====<br />
Though most patients with <i>C. difficile</i> can recover without specific therapy, symptoms may be particularly debilitating and drawn out. The elderly are much more susceptible to severe infection, and the mortality rate in this demographic is estimated to be as high as 25%. The disease’s mortality and morbidity seems to have increased in severity in the last decade. The CDC has reported that enteritis deaths more than doubled from 1997 to 2007 in the United States, increasing to 17,000 from about 7,000, and C difficile was associated with 14,500 of these deaths, up from 2,700 in 1999 [[#References|[5]]]. A particularly virulent strain has been traced to several outbreaks in North America, known as the NAP1/027 strain. It shows increased production of toxins A and B, antibiotic resistance, and the production of a binary toxin whose role is not yet clear, but is thought to increase the virulence of the A and B toxins.<br />
<br />
===Virulence factors===<br />
<i>C. difficile</i> expresses two toxins, toxin A (TcdA) and toxin B (TcdB), which are two of the largest bacterial toxins known (review). They are part of the Large Clostridial Toxin family, in which the toxins glucosylate small GTPases in the cytosol of targeted cells. Both toxins disrupt the actin cytoskeleton of fibroblasts and prevent cells from being able to regulate actin polymerization. Toxin A produces a florid inflammatory response, while B has no enterotoxin activity, but instead is a potent cytotoxin. In fact, toxin B is 10 times more potent than A in causing damage in colonic epithelial cells, which points to toxin B as the primary virulence factor. Which of the two is the primary virulence factor has been disputed and was previously thought to be toxin A, but recent evidence points towards toxin B.<br />
<br />
==Clinical features==<br />
<br />
Colonization of the intestine by <i>Clostridium difficile</i> can occur without presenting any symptoms in the host, however, infection can cause symptoms ranging from trivial diarrhea to serious manifestations of disease. General symptoms of CDAD include watery diarrhea, fever, loss of appetite, nausea, and abdominal pain/tenderness, but grossly bloody stools are unusual. Signs of more advanced disease include pseudomembranous colitis, toxic megacolon (also known as colonic distention), perforations of the colon, sepsis, and sometimes death. <br><br><br />
One of the most well recognized manifestations of the disease, pseudomembranous colitis, was first described in 1893 and is the formation of lesions within the colon that are made of a pseudomembrane of immune cells, mucus, and necrotic tissue [[#References|[4]]]. For 20% of patients with advanced CDAD: diarrhea and fluid loss are minimal, and instead, abdominal distention and bowel obstruction can lead to misdiagnosis. For other patients, signs of systemic toxicity and systemic inflammatory syndrome, including leukocytosis, rising serum lactate levels, hypotension, acute renal failure, and respiratory distress, lead to poor prognosis and high mortality rates. Fulminant colitis can lead to the need for a total colectomy, but even with this procedure, the average mortality rate at this stage of the disease is 67%, and the progression from initial symptoms to this stage can occur in as little as hours to as much as weeks.<br />
<br />
==Diagnosis==<br />
<br />
Prior to testing for <i>Clostridium difficile</i>, there are three predominate indications for the presumption of a <i>C. difficile</i> infection (CDI). Patients are most susceptible if they have received antibiotics within the last 8-12 weeks; patients are over the age of 64; patients have produced 3 or more diarrheal stools within 24 hours. The most widely accepted method used to test for CDI is a toxigenic culture involving the incubation of a fecal culture and subsequent immunoassay to test for the presence of <i>C. difficile</i> toxin A [[#References|[6,7]]]. <br />
PCR is becoming a more popular method to identify toxins A and B because of its specificity, sensitivity, and rapid results. However, physicians warn that false positives are easily obtained from asymptomatic individuals. For this reason, physicians and researchers direct only to test diarrheal stool, especially from individuals who identify with any of the three preliminary traits listed above [[#References|[6]]].<br />
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The application of a two-step technique involving an enzyme immunoassay (EIA) and a confirmatory step to detect the presence of <i>C. difficile</i> toxins in stool samples has also proven effective in clinical laboratories. The EIA is used to detect glutamate dehydrogenase (GDH); positive samples are then subject to toxigenic culturing. However, this method still requires further confirmation to determine the relative sensitivity and consistency among GDH test kits ([[#References|[6,7]]].<br />
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In comparison to the EIA technique, the tissue cytotoxin assay shows higher specificity for toxin detection, but is a more complex and time intensive procedure. Tissue cytotoxin assays are considered inefficient in clinical settings [[#References|[6]]].<br />
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Repeat testing from a single stool sample is not encouraged due to the increased risk for false-positive results [[#References|[6,7]]]. Additionally, retesting a recently recovered patient may produce misleading results since <i>C. difficile</i> likely remains colonized for a period of time after CDI symptoms subside [[#References|[6]]].<br />
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==Treatment==<br />
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===Non-severe cases===<br />
For non-severe cases, the first step in treatment is the cessation of the inciting antibiotic as soon as possible and only continuing concomitant antibiotics if they are prudent to the treatment of the initial infection. Oral metronidazole or vancomycin are typically administered. However, some literature points to vancomycin having increased efficacy over metronidazole [[#References|[8]]].<br />
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===Moderate to severe cases===<br />
<b>Antibiotics:</b><br><br />
For more severe cases higher, more frequent doses of vancomycin (either oral or rectal) are administered. However, rectal doses have a higher risk of producing colonic perforations and should only be administered when oral preparations are impossible for the patient.<br />
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<b>Fecal Transplantation:</b><br><br />
Another method of treatment is the infusion of a purified stool substitute preparation from a healthy donor. Generally, fecal transplantation is used in cases where the patient has had multiple recurrent infections and both metronidazole and vancomycin fail. It is reasonably successful in repopulating the gut with commensal bacteria and combating antibiotic resistant CDAD [[#References|[9]]].<br />
<br><br><br />
<b>Probiotics:</b><br><br />
Antibiotics function to alter the intestinal flora in order to produce an unfavorable environment for <i>C. difficile</i>. Some Lactobacilli, in particular, <i>S. boulardii,</i> have been shown to suppress <i>C. difficile</i> growth in hamsters. Furthermore, temporarily populating the gut with particular Lactobacilli can lower the pH of the surrounding environment and secrete degradation enzymes like proteases that place stress on the <i>C. difficile</i> population. Finally, some strains of beneficial bacteria may have the ability to protect the intestinal barrier by interfering TcdA and TcdB binding to the host gut epithelium [[#References|[10]]].<br />
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<b>Immunomodulation:</b><br><br />
New research suggests that the supplementation of laboratory-derived monoclonal antibodies may have the ability to inhibit <i>C. difficile</i> colonization by stimulating toll-like receptors and upregulating expression of dendritic cells and peripheral blood monocytes [[#References|[11]]].<br />
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<b>Surgery:</b><br><br />
Some severely ill patients with CDAD may require surgical intervention as a result of toxic megacolon, colonic perforations, necrotizing colitis, or infections producing systemic inflammatory responses that could potentially lead to organ failure. In these cases, diseased portions of the gastrointestinal tract are removed.<br />
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==Prevention==<br />
Prevention with good hygiene habits will go a long way to protect against opportunistic pathogens like C. difficile. The main focus with C. difficile specifically should be on more conscientious antibiotic use, as broad spectrum antibiotics make patients susceptible in the first place. Restricting antibiotic use should lower the incidence of the disease and hopefully slow its growing virulence. When dealing with CDAD patients in a hospital setting, isolation of the sick, proper hand washing techniques, protective gowns and gloves, and cleaning with sodium hypochlorite are all important and effective ways to prevent outbreaks in healthcare settings. Work on a vaccine has begun, which appears to be promising, but is still far from market availability.<br />
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==Host Immune Response==<br />
The pathophysiology of <i>C. difficile</i> is directly related to the host immune response to CDI. <i>C. difficile</i> colonizes in the lumen of the small intestine where it can lie dormant by means of sporulation, or it produces enterotoxins TcdA and TcdB, eliciting an inflammatory immune response. Toxin A attracts polymorphonuclear cells (PMNs) or neutrophils to the site of infection via cytokines from epithelial host cells. This influx of leukocytes as a function of the immune response increases vascular permeability, allowing TcdA and TcdB to cross the mucosal membrane. TcdB degrades colonic epithelial cells. Accumulations of leukocytes form a pseudomembrane on the lining of the colon (pseudomembranous colitis).<br><br><br />
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Current research suggests that upon exposure to <i>C. difficile</i>, humans develop an adaptive immunity to TcdA and TcdB. It is estimated that approximately 60% of healthy adults exhibit IgG and IgA antibodies against C. difficile toxins. Studies suggest that adaptive immunity can begin in childhood from environmental exposure to <i>C. difficile</i>, and possibly non-toxigenic clostridial species [[#References|[13,14]]]. Studies show that immunoglobulin A (IgA) antibody inhibits TcdA binding to epithelial cells in the colon [[#References|[12]]]. Moreover, higher levels of IgA and IgG anti-toxins were found in asymptomatic patients, as well as those who displayed minor symptoms of CDAD [[#References|[13,14]]].<br />
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==References==<br />
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1. Larson HE, Price AB, Honour P, Borriello SP: <i>Clostridium difficile</i> and the aetiology of pseudomembranous colitis. <i>Lancet</i> 1978, 1: 1063-1066. <br><br />
2. Pepin J, Alary ME, Valiquette L, Raiche E, Ruel J, Godin D, Bourassa C: Increasing risk of relapse after treatment of <i>Clostridium difficile</i> colitis in Quebec, Canada. <i>Clin Infect Dis</i>. 2005 Jun 1; 40(11): 1591-7.<br><br />
3. LaMont JT, Calderwood SB, et al.: <i>Clostridium difficile</i> in adults: Clinical manifestations and diagnosis. UpToDate June 2013, Available at: http://www.uptodate.com/contents/clostridium-difficile-in-adults-clinical-manifestations-and-diagnosis.<br><br />
4. CDC. Vital Signs: Preventing Clostridium difficile Infections. <i>MMWR Morb Mortal Wkly Rep</i>. Mar 9 2012;61:157-62. [Medline].<br><br />
5. Centers for Disease Control and Prevention (CDC). Deaths from gastroenteritis double. Available at http://www.cdc.gov/media/releases/2012/p0314_gastroenteritis.html.<br><br />
6. Gould, Carolyn. CDC Commentary: Testing for <i>Clostridium difficile</i> Infection. <i>Medscape</i>. Aug 16, 2010.<br><br />
7. Cohen S., Gerding D., Johnson S., Kelly C., Loo V., McDonald L., Pepin J., Wilcox M. (2010). Clinical Practice Guidelines for <i>Clostridium difficile</i> Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America. <i>Infection Control and Hospital Epidemiology</i> 31(5):431-455. <br><br />
8. Bolton RP, Culshaw MA. Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to <i>Clostridium difficile</i>. Gut 1986; 27: 1169.<br><br />
9. Petrof EO, Gloor GB, Vanner SJ et al. Stool substitute transplant therapy for the eradication of <i>Clostridium difficile</i> infection: ‘RePOOPulating’ the gut. <i>Microbiome</i> 2013 January; 1:3<br><br />
10. Sartor RB, LaMont JT, Probiotics for gastrointestinal diseases. UpToDate June 2013, Available at: http://www.uptodate.com/contents/probiotics-for-gastrointestinal-diseases?source=see_link&anchor=H7#H7<br><br />
11. Lowy I, Molrine DC, Leav BA, et al. Treatment with monoclonal antibodies against <i>Clostridium difficile</i> toxins. N Engl J Med 2010; 362:197.<br><br />
12. Kelly C. P., Pothoulakis C., Orellana J., Lamont J.T. (1992). Human colonic aspirates containing immunoglobulin A antibody to <i>Clostridium difficile</i> toxin A inhibit toxin A-receptor binding. <i>Gastroenterology</i> 102, 35-40. Pmid:1309359.<br />
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13. Kyne L., Warny M., Qamar A., Kelly C.P. (2000). Asymptomatic carriage of <i>Clostridium difficile</i> and serum levels of IgG antibody against toxin A. <i>N Engl J Med</i> 342, 390-397. <br />
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14. Viscidi R, Laughon BE, Yolken R, et al. Serum antibody response to toxins A and B of <i>Clostridium<br />
difficile</i>. J Infect Dis 1983;148:93–100. [PubMed: 6886489]<br />
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Created by Laura Boucher, Marrett Hild, and Lillian Flannigan, students of Tyrrell Conway at the University of Oklahoma</div>Halen.M.Borron-1