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| __NOTOC__
| | #REDIRECT[[Borrelia burgdorferi]] |
| {{Lyme disease}}
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| {{Seealso|Borrelia}}
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| {{CMG}}
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| ==Overview==
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| [[Image:Borrelia image.jpg|thumb|left|''Borrelia burgdorferi'' the causative agent of Lyme disease (borreliosis). Magnified 400 times.]]
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| '''[[Lyme disease]]''', or '''[[Lyme borreliosis]]''', is caused by [[Gram negative]] [[spirochetal]] [[bacteria]] from the [[genus]] ''[[Borrelia]]'', which has at least 37 known species, 12 of which are Lyme related, and an unknown number of genomic [[strain (biology)|strains]]. ''Borrelia'' [[species]] known to cause Lyme disease are collectively known as ''[[Borrelia burgdorferi]]'' sensu lato.
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| ''Borrelia'' are [[Microaerophile|microaerophillic]] and slow-growing—the primary reason for the long delays when diagnosing Lyme disease—and have been found to have greater [[genetic diversity|strain diversity]] than previously estimated.<ref name="Bunikis-a">{{cite journal | author=Bunikis J, Garpmo U, Tsao J, Berglund J, Fish D, Barbour AG | title=Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe | journal=Microbiology | year=2004 | pages=1741-55 | volume=150 | issue=Pt 6 | pmid = 15184561 | url=http://mic.sgmjournals.org/cgi/reprint/150/6/1741.pdf | format=PDF}}</ref> The strains differ in clinical symptoms and/or presentation as well as geographic distribution.<ref name=Sherris>{{cite book | author = Ryan KJ, Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | publisher = McGraw Hill | year = 2004 | isbn = 0-8385-8529-9 }}</ref>
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| Except for ''Borrelia recurrentis'' (which causes louse-borne [[relapsing fever]] and is transmitted by the human body louse), all known species are believed to be transmitted by ticks.<ref>{{cite book | author = Felsenfeld O |title = Borrelia: Strains, Vectors, Human and Animal Borreliosis| location = St. Louis | publisher = Warren H. Green, Inc | year = 1971}}</ref>
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| ==Species and Strains==
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| Until recently it was thought that only three genospecies caused Lyme disease (borreliosis): ''B. burgdorferi'' sensu stricto ( the predominant species in North America, but also present in Europe); ''B. afzelii''; and ''B. garinii'' (both predominant in Eurasia). To date the complete [[genome]] of ''B. burgdorferi'' sensu stricto strain B31, B. afzelii strain PKo and B. garinii strain PBi is known. ''B. burgdorferi'' strain B31 was derived by limited dilutional cloning from the original Lyme-disease tick isolate derived by Alan Barbour. There are over 300 species or strains of Borrelia world wide with apx 100 in the U.S. and it is unknown how many cause lyme like sickness, but many of them may.
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| At present, [[diagnostic]] tests are based only on ''B. burgdorferi'' sensu stricto (the only species used in the U.S.), ''B. afzelii'', and ''B. garinii''.
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| ===Emerging Genospecies===
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| * ''B. valaisiana'' was identified as a genomic species from Strain VS116, and named B. valaisiana in 1997.<ref>{{cite journal |author=Wang G, van Dam AP, Le Fleche A, ''et al'' |title=Genetic and phenotypic analysis of Borrelia valaisiana sp. nov. (Borrelia genomic groups VS116 and M19) |journal=Int. J. Syst. Bacteriol. |volume=47 |issue=4 |pages=926-32 |year=1997 |pmid=9336888 |doi=}}</ref> It was later detected by [[Polymerase chain reaction]] (PCR) in human [[cerebral spinal fluid]] (CSF) in Greece.<ref name="Diza">{{cite journal |author=Diza E, Papa A, Vezyri E, Tsounis S, Milonas I, Antoniadis A |title=Borrelia valaisiana in cerebrospinal fluid |journal=Emerging Infect. Dis. |volume=10 |issue=9 |pages=1692-3 |year=2004 |pmid=15503409 |url=http://www.cdc.gov/ncidod/EID/vol10no9/03-0439.htm}}</ref> ''B. valaisiana'' has been isolated throughout Europe, as well east Asia.<ref>{{cite journal |author=Masuzawa T |title=Terrestrial distribution of the Lyme borreliosis agent Borrelia burgdorferi sensu lato in East Asia |journal=Jpn. J. Infect. Dis. |volume=57 |issue=6 |pages=229-35 |year=2004 |pmid=15623946 |doi=}}</ref>
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| Newly discovered genospecies have also been found to cause disease in humans:
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| *''B. lusitaniae'' <ref name="Collares">{{cite journal | author=Collares-Pereira M, Couceiro S, Franca I, Kurtenbach K, Schafer SM, Vitorino L, Goncalves L, Baptista S, Vieira ML, Cunha C | title=First isolation of Borrelia lusitaniae from a human patient | journal=J Clin Microbiol | year=2004 | pages=1316-8 | volume=42 | issue=3 | id=PMID 15004107 | url=http://jcm.asm.org/cgi/reprint/42/3/1316.pdf | format=PDF}}</ref> in Europe (especially Portugal), North Africa and Asia.
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| *''B. bissettii'' <ref name="Postic">{{cite journal | author=Postic D, Ras NM, Lane RS, Hendson M, Baranton G | title=Expanded diversity among Californian borrelia isolates and description of Borrelia bissettii sp. nov. (formerly Borrelia group DN127) | journal=J Clin Microbiol | year=1998 | pages=3497-504 | volume=36 | issue=12 | id=PMID 9817861 | url=http://jcm.asm.org/cgi/reprint/36/12/3497.pdf | format=PDF}}</ref><ref name="Maraspin">{{cite journal | author=Maraspin V, Cimperman J, Lotric-Furlan S, Ruzic-Sabljic E, Jurca T, Picken RN, Strle F | title=Solitary borrelial lymphocytoma in adult patients | journal=Wien Klin Wochenschr | year=2002 | pages=515-23 | volume=114 | issue=13-14 | id=PMID 12422593}}</ref> in the U.S. and Europe.
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| *''B. spielmanii'' <ref name="Richter">{{cite journal | author=Richter D, Postic D, Sertour N, Livey I, Matuschka FR, Baranton G | title=Delineation of Borrelia burgdorferi sensu lato species by multilocus sequence analysis and confirmation of the delineation of Borrelia spielmanii sp. nov | journal=Int J Syst Evol Microbiol | year=2006 | pages=873-81 | volume=56 | issue=Pt 4 | id=PMID 16585709}}</ref><ref name="Foldvari">{{cite journal | author=Foldvari G, Farkas R, Lakos A | title=Borrelia spielmanii erythema migrans, Hungary | journal=Emerg Infect Dis | year=2005 | pages=1794-5 | volume=11 | issue=11 | id=PMID 16422006 | url=http://www.cdc.gov/ncidod/EID/vol11no11/05-0542.htm}}</ref> in Europe.
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| Additional ''B. burgdorferi'' sensu lato genospecies suspected of causing illness, but not confirmed by culture, include B. japonica, B. tanukii and B. turdae (Japan); B. sinica (China); and ''B. andersonii'' (U.S.). Some of these species are carried by ticks not currently recognized as carriers of Lyme disease.
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| The ''B. miyamotoi'' spirochete, related to the [[relapsing fever]] group of spirochetes, is also suspected of causing illness in Japan. Spirochetes similar to B. miyamotoi have recently been found in both I. ricinus ticks in Sweden and I. scapularis ticks in the U.S.<!--
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| --><ref name="Scoles">{{cite journal | author=Scoles GA, Papero M, Beati L, Fish D | title=A relapsing fever group spirochete transmitted by Ixodes scapularis ticks | journal=Vector Borne Zoonotic Dis | year=2001 | pages=21-34 | volume=1 | issue=1 | id=PMID 12653133}}</ref><!--
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| --><ref name="Bunikis-b">{{cite journal | author=Bunikis J, Tsao J, Garpmo U, Berglund J, Fish D, Barbour AG | title=Typing of Borrelia relapsing fever group strains | journal=Emerg Infect Dis | year=2004 | pages=1661-4 | volume=10 | issue=9 | id=PMID 15498172}}</ref>
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| ===B. lonestari===
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| Apart from this group of closely related genospecies, additional Borrelia species of interest include B. lonestari, a spirochete recently detected in the Amblyomma americanum tick (Lone Star tick) in the U.S.<!--
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| --><ref name="Varela">{{cite journal | author=Varela AS, Luttrell MP, Howerth EW, Moore VA, Davidson WR, Stallknecht DE, Little SE | title=First culture isolation of Borrelia lonestari, putative agent of southern tick-associated rash illness | journal=J Clin Microbiol | year=2004 | pages=1163-9 | volume=42 | issue=3 | id=PMID 15004069 | url=http://jcm.asm.org/cgi/reprint/42/3/1163.pdf | format=PDF}}</ref><!--
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| --> ''B. lonestari'' is suspected of causing STARI (Southern Tick-Associated Rash Illness), also known as Masters disease in honor of its discoverer Ed Masters. The illness follows a Lone Star tick bite and clinically resembles Lyme disease, but sufferers usually test negative for Lyme.<!--
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| --><ref name="Masters">{{cite journal | author=Masters E, Granter S, Duray P, Cordes P | title=Physician-diagnosed erythema migrans and erythema migrans-like rashes following Lone Star tick bites | journal=Arch Dermatol | year=1998 | pages=955-60 | volume=134 | issue=8 | id=PMID 9722725}}</ref>There is currently no diagnostic test available for STARI/Masters, and no official treatment protocol, though antibiotics are generally prescribed.
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| ==Genomic characteristics==
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| One of the most striking features of ''B. burgdorferi'' as compared with other [[eubacteria]] is its unusual [[genome]], which is far more complex than that of its spirochetal cousin ''[[Treponema pallidum]]'', the agent of [[syphilis]].<!--
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| --><ref name="Porcella">{{cite journal | author=Porcella SF, Schwan TG | title=Borrelia burgdorferi and Treponema pallidum: a comparison of functional genomics, environmental adaptations, and pathogenic mechanisms | journal=J Clin Invest | year=2001 | pages=651-6 | volume=107 | issue=6 | id=PMID 11254661 | url=http://www.jci.org/cgi/content/full/107/6/651}}</ref>
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| The genome of ''B. burgdorferi'' includes a linear [[chromosome]] approximately one [[megabase]] in size, with 21 [[plasmids]] (12 linear and 9 circular) - by far the largest number of plasmids found in any known bacterium.<!--
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| --><ref name="Casjens">{{cite journal | author=Casjens S, Palmer N, van Vugt R, Huang WM, Stevenson B, Rosa P, Lathigra R, Sutton G, Peterson J, Dodson RJ, Haft D, Hickey E, Gwinn M, White O, Fraser CM | title=A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi | journal=Mol Microbiol | year=2000 | pages=490-516 | volume=35 | issue=3 | id=PMID 10672174 | url=http://www.blackwell-synergy.com/doi/full/10.1046/j.1365-2958.2000.01698.x}}</ref>
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| Genetic exchange, including plasmid transfers, contributes to the [[pathogenicity]] of the organism.<!--
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| --><ref name="Qiu">{{cite journal | author=Qiu WG, Schutzer SE, Bruno JF, Attie O, Xu Y, Dunn JJ, Fraser CM, Casjens SR, Luft BJ | title=Genetic exchange and plasmid transfers in Borrelia burgdorferi sensu stricto revealed by three-way genome comparisons and multilocus sequence typing | journal=Proc Natl Acad Sci U S A | year=2004 | pages=14150-5 | volume=101 | issue=39 | id=PMID 15375210 | url=http://www.pnas.org/cgi/reprint/101/39/14150.pdf | format=PDF}}</ref>
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| Long-term culture of ''B. burgdorferi'' results in a loss of some plasmids and changes in expressed protein profiles. Associated with the loss of plasmids is a loss in the ability of the organism to infect laboratory animals, suggesting that the plasmids encode key genes involved in [[virulence]].
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| Chemical analysis of the external membrane of ''B. burgdorferi'' revealed the presence of 46% proteins, 51% lipids and 3% carbohydrates.<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8348630&query_hl=5&itool=pubmed_docsumSchwarzova ]K. "Lyme borreliosis: review of present knowledge"
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| Cesk Epidemiol Mikrobiol Imunol. 1993 Jun;42(2):87-92.</ref>
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| ==Advancing Immunology Research==
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| {{See| Lyme Disease#Advancing Immunology Research}}
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| The role of [[T cells]] in borrelia was first made in 1984,<ref>Newman K Jr, Johnson RC."T-cell-independent elimination of Borrelia turicatae".Infect Immun. 1984 Sep;45(3):572-6.</ref> the role of cellular immunity in active Lyme disease was made in 1986,<ref>Dattwyler RJ, Thomas JA, Benach JL, Golightly MG."Cellular immune response in Lyme disease: the response to mitogens, live Borrelia burgdorferi, NK cell function and lymphocyte subsets". Zentralbl Bakteriol Mikrobiol Hyg [A]. 1986 Dec;263(1-2):151-9</ref> and long term persistence of T cell [[lymphocyte]] responses to ''B. burgdorferi'' as an "immunological scar syndrome" was hypothesized in 1990.<ref>Kruger H, Pulz M, Martin R, Sticht-Groh V. "Long-term persistence of specific T- and B-lymphocyte responses to Borrelia burgdorferi following untreated neuroborreliosis".
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| Infection. 1990 Sep-Oct;18(5):263-7.</ref> The role [[Th1]] and [[interferon-gamma]] (INF-gamma) in borrelia was first described in 1995.<ref>Forsberg P, Ernerudh J, Ekerfelt C, Roberg M, Vrethem M, Bergstrom S. "The outer surface proteins of Lyme disease borrelia spirochetes stimulate T cells to secrete interferon-gamma (IFN-gamma): diagnostic and pathogenic implications".
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| Clin Exp Immunol. 1995 Sep;101(3):453-60.</ref> The [[cytokine]] pattern of Lyme disease, and the role of Th1 with down regulation of [[interleukin-10]] (IL-10) was first proposed in 1997.<ref> Yin Z, Braun J, Neure L, Wu P, Eggens U, Krause A, Kamradt T, Sieper J. "T cell cytokine pattern in the joints of patients with Lyme arthritis and its regulation by cytokines and anticytokines". Arthritis Rheum. 1997 Jan;40(1):69-79.</ref>
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| Recent studies in both acute and antibiotic refractory, or chronic, Lyme disease have shown a distinct [[inflammation|pro-inflammatory]] immune process. This pro-inflammatory process is a [[cell-mediated immunity]] and results in Th1 upregulation. These studies have shown a significant decrease in [[cytokine]] output of (IL-10), an upregulation of [[Interleukin-6]] (IL-6) and [[Interleukin-12]] (Il-12) and [[Interferon-gamma]] (IFN-gamma) and disregulation in [[TNF-alpha]] predominantly.
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| New research has also found that chronic Lyme patients have higher amounts of Borrelia-specific [[FoxP3|forkhead box P3]] (FoxP3) than healthy controls, indicating that [[regulatory T cell]]s might also play a role, by [[immunosuppression]], in the development of chronic Lyme disease. FoxP3 are a specific marker of regulatory T cells.<ref>Jarefors S, Janefjord CK, Forsberg P, Jenmalm MC, Ekerfelt C. "Decreased up-regulation of the interleukin-12Rbeta2-chain and interferon-gamma secretion and increased number of forkhead box P3-expressing cells in patients with a history of chronic Lyme borreliosis compared with asymptomatic Borrelia-exposed individuals." Clin Exp Immunol. 2007 Jan;147(1):18-27</ref> The signaling pathway [[P38 mitogen-activated protein kinases]] (p38 MAP kinase) has also been identified as promoting expression of proinflammatory cytokines from borrelia.<ref>Olson CM, Hedrick MN, Izadi H, Bates TC, Olivera ER, Anguita J. "p38 mitogen-activated protein kinase controls NF-kappaB transcriptional activation and tumor necrosis factor alpha production through RelA phosphorylation mediated by mitogen- and stress-activated protein kinase 1 in response to Borrelia burgdorferi antigens." Infect Immun. 2007 Jan;75(1):270-7. Epub 2006 Oct 30.</ref><ref>Ramesh G, Philipp MT. "Pathogenesis of Lyme neuroborreliosis: mitogen-activated protein kinases Erk1, Erk2, and p38 in the response of astrocytes to Borrelia burgdorferi lipoproteins". Neurosci Lett. 2005 Aug 12-19;384(1-2):112-6</ref>
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| The culmination of these new and ongoing immunological studies suggest this cell-mediated immune disruption in the Lyme patient amplifies the inflammatory process, often rendering it chronic and self-perpetuating, regardless of whether the borrelia bacterium is still present in the host, or in the absence of the inciting pathogen in an [[autoimmune]] pattern.<ref>{{cite journal |author=Singh SK, Girschick HJ |title=Toll-like receptors in Borrelia burgdorferi-induced inflammation |journal=Clin. Microbiol. Infect. |volume=12 |issue=8 |pages=705-17 |year=2006 |pmid=16842565 |doi=10.1111/j.1469-0691.2006.01440.x}}</ref>
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| ==References==
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| {{Reflist|2}}
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| ==External links==
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| *[http://www.molecularalzheimer.org/Atlasof_borrelia.html Atlas of Borrelia (images of spirochetal, spheroplast and granular forms)]
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| *[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=138 NCBI Taxonomy Browser - Borrelia]
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| *[http://cmr.tigr.org/tigr-scripts/CMR/GenomePage.cgi?database=gbb Borrelia burgdoferi B31 Genome Page]
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| *[http://cmr.tigr.org/tigr-scripts/CMR/GenomePage.cgi?org=ntbg01 Borrelia Garinii PBi Genome Page]
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| *[http://cmr.tigr.org/tigr-scripts/CMR/GenomePage.cgi?org=ntba07 Borrelia Afzelli PKo Gemonme Page]
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| *[http://www.cdc.gov/ncidod/eid/vol8no2/01-0198.htm CDC - Vector Interactions and Molecular Adaptations of Lyme Disease and Relapsing Fever Spirochetes Associated with Transmission by Ticks]
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| [[de:Wanderröte]]
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| [[nl:Borrelia burgdorferi]]
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| [[no:Borrelia]]
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| [[pt:Borrelia burgdorferi]]
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| [[uk:Borrelia burgdorferi]]
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| [[zh:伯氏疏螺旋體]]
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| [[Category:Lyme disease]]
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| [[Category:Spirochaetes]]
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| [[Category:Insect-borne diseases]]
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| [[Category:Zoonoses]]
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| [[Category:Immunology]]
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| [[Category:Infectious disease|Infectious diseases]]
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| [[Category:Microbiology|*]]
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| [[pl:Borrelia burgdorferi]] | |
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| {{WH}}
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| {{WS}}
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| {{jb1}}
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