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__NOTOC__
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{{Lyme disease}}
{{Lyme disease}}
{{CMG}}{{AE}}{{Anmol}}
{{CMG}} {{AE}} {{IMD}}
==Overview==
==Overview==
[[Lyme disease]] is caused by ''[[Borrelia burgdorferi]]'' and is [[Transmission|transmitted]] primarily by [[tick]] named [[Ixodes scapularis]]. [[Ticks]] can attach to any part of the human body but are often found in hard-to-see areas such as the [[groin]], [[armpits]], and [[scalp]]. In most cases, the [[tick]] must be attached for 36 to 48 hours or more before the [[spirochetes]] can be transmitted. Very few people affected with [[lyme disease]] recall a [[tick]] bite. ''[[B. burgdorferi]]'' is known to [[invasion|invade]] a variety of [[cells]] in humans. By 'hiding' inside these cells, ''[[B. burgdorferi]]'' is able to evade the [[immune system]] and is protected to varying degrees against [[antibiotics]]. ''[[B. burgdorferi]]'' altered [[morphology (biology)|morphological]] forms, i.e. [[spheroplast]]s ([[cysts]], [[granules]]). ''[[B. burgdorferi]]'' has the ability to vary its [[surface proteins]] in response to [[immune system|immune]] attack. Various survival strategies of ''[[B. burgdorferi]]'' includes physical sequestration in [[tissues]] and immune system suppression.
Lyme disease is the most common tick borne disease in North America and the the ratio of Lyme disease infection is 7.9 cases for every 100,000 persons. The number of people diagnosed with Lyme disease each year in the United States is around 300,000. This disease is concentrated heavily in the northeast and upper mid-west.  
==Epidemiology and Demographics==


==Pathophysiology==
==Prevalence==
===Transmission===
[[Image:Ixodes scapularis.png|left|150px|''[[Ixodes scapularis]]'', the primary vector of Lyme disease in eastern North America.]]


<br clear="left" />
===Incidence===
====Primary Vector====
*Lyme disease is the most common [[tick-borne disease]] in North America and Europe, and one of the fastest-growing [[infectious diseases]] in the United States.  
*Hard-bodied [[tick]]s of the genus ''[[Ixodes]]'' are the primary [[vector (biology)|vectors]] of Lyme disease.
*Of cases reported to the United States Center for Disease Control (CDC), the ratio of Lyme disease infection is 7.9 cases for every 100,000 persons.  
*Majority of Ixodes-vectored human disease are caused by ''I. scapularis'', ''I. pacificus'', ''I. ricinus'', and ''I. persulcatus''. So, they are also known as 'bridge' vectors.<ref name="pmid21890064">{{cite journal| author=Rudenko N, Golovchenko M, Grubhoffer L, Oliver JH| title=Updates on Borrelia burgdorferi sensu lato complex with respect to public health. | journal=Ticks Tick Borne Dis | year= 2011 | volume= 2 | issue= 3 | pages= 123-8 | pmid=21890064 | doi=10.1016/j.ttbdis.2011.04.002 | pmc=3167092 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21890064  }} </ref>
*In the ten states where Lyme disease is most common, the average was 31.6 cases for every 100,000 persons for the year 2005.<ref>{{cite web | url = http://www.cdc.gov/ncidod/dvbid/lyme/ld_UpClimbLymeDis.htm | author = CDC | title = Reported Cases of Lyme Disease by Year, United States, 1991-2005 | date = 2006-10-02 | accessdate = 2007-08-20}}</ref>
*Adult ticks are more infected then nymph stage by pathogens infectious to humans.<ref name="SchwartzFish1997">{{cite journal|last1=Schwartz|first1=Ira|last2=Fish|first2=Durland|last3=Daniels|first3=Thomas J.|title=Prevalence of the Rickettsial Agent of Human Granulocytic Ehrlichiosis in Ticks from a Hyperendemic Focus of Lyme Disease|journal=New England Journal of Medicine|volume=337|issue=1|year=1997|pages=49–50|issn=0028-4793|doi=10.1056/NEJM199707033370111}}</ref> But the majority of infections are caused by ticks in the nymph stage during late spring and summer.<ref name="pmid10206627">{{cite journal| author=Falco RC, McKenna DF, Daniels TJ, Nadelman RB, Nowakowski J, Fish D et al.| title=Temporal relation between Ixodes scapularis abundance and risk for Lyme disease associated with erythema migrans. | journal=Am J Epidemiol | year= 1999 | volume= 149 | issue= 8 | pages= 771-6 | pmid=10206627 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10206627  }} </ref>
*Although Lyme disease has now been reported in 49 of 50 states in the U.S, about 99% of all reported cases are confined to just five geographic areas including New England, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central.
*In most cases, the tick must be attached for 36 to 48 hours or more before the spirochetes can be transmitted.<ref name="pmid2010643">{{cite journal| author=Piesman J, Maupin GO, Campos EG, Happ CM| title=Duration of adult female Ixodes dammini attachment and transmission of Borrelia burgdorferi, with description of a needle aspiration isolation method. | journal=J Infect Dis | year= 1991 | volume= 163 | issue= 4 | pages= 895-7 | pmid=2010643 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2010643  }} </ref>. It takes atleast 36 hours for spirohetes to multiply and migrate to salivary glands from mid gut.<ref name="pmid11209063">{{cite journal| author=Ohnishi J, Piesman J, de Silva AM| title=Antigenic and genetic heterogeneity of Borrelia burgdorferi populations transmitted by ticks. | journal=Proc Natl Acad Sci U S A | year= 2001 | volume= 98 | issue= 2 | pages= 670-5 | pmid=11209063 | doi=10.1073/pnas.98.2.670 | pmc=14646 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11209063  }} </ref>
[[Image:Reported cases of lyme disease in usa from 2001-2015.gif|center|750px|frame|Reported cases of Lyme disease in the United Stated from 2001 to 2015]]
*In Europe and Pacific region of North America, the commonly known sheep tick, castor bean tick, or European castor bean tick (''[[Ixodes ricinus]]'') is the transmitter.<ref name="pmid21890064">{{cite journal| author=Rudenko N, Golovchenko M, Grubhoffer L, Oliver JH| title=Updates on Borrelia burgdorferi sensu lato complex with respect to public health. | journal=Ticks Tick Borne Dis | year= 2011 | volume= 2 | issue= 3 | pages= 123-8 | pmid=21890064 | doi=10.1016/j.ttbdis.2011.04.002 | pmc=3167092 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21890064  }} </ref>
*In North America, the black-legged tick or deer tick (''Ixodes scapularis'') has been identified as the key to the disease's spread on the east coast.  
*About 20% of individuals infected with Lyme disease by the deer tick are aware of having had any tick bite, making early detection difficult in the absence of a rash.<ref name="Wormser">{{cite journal | author=Wormser G, Masters E, Nowakowski J, ''et al'' | title=Prospective clinical evaluation of patients from missouri and New York with erythema migrans-like skin lesions. | journal=Clin Infect Dis | volume=41 | issue=7 | pages=958-65 | year=2005 | pmid= 16142659}}</ref>


====Other Potential Vectors====
===Widespread disease and endemic regions===
*The lone star tick (''Amblyomma americanum''), which is found throughout the southeastern U.S. as far west as Texas, and increasingly in northeastern states as well.<ref name="Clark">{{cite journal | author=Clark K | title=''Borrelia'' species in host-seeking ticks and small mammals in northern Florida. | journal=J Clin Microbiol | volume=42 | issue=11 | pages=5076-86 | year=2004 | pmid= 15528699 | url=http://jcm.asm.org/cgi/reprint/42/11/5076.pdf | format=PDF}}</ref>
*The number of reported cases of [[Disease|the disease]] have been increasing, as are endemic regions in North America.  
*These tick bites usually go unnoticed due to the small size of the tick in its nymphal stage, as well as tick secretions that prevent the host from feeling any itch or pain from the bite.
*''B. burgdorferi'' sensu lato has been maintained in enzootic cycles in California as well as other regions throughout North America, Europe and North Africa. Indeed, the [[DNA]] of ''[[Borrelia]]'' has been detected in lizards, indicating that they can be infected.<ref>{{cite journal |author=Swanson KI, Norris DE |title=Detection of Borrelia burgdorferi DNA in lizards from Southern Maryland |journal=Vector Borne Zoonotic Dis. |volume=7 |issue=1 |pages=42-9 |year=2007 |pmid=17417956 |doi=10.1089/vbz.2006.0548}}</ref>  
*It was once thought to be a vector, although recent studies demonstrate that this tick species is not a competent vector of ''Borrelia burgdorferi'' sensu lato.<ref name="Ledin-k">{{cite journal | author = Ledin K, Zeidner N, Ribeiro J, "et al" | title = Borreliacidal activity of saliva of the tick Amblyomma americanum. | journal = Med Vet Entomol | volume = 19 | issue = 1 | pages = 90-95 | year = 2005 | pmid = 15752182}}</ref>  


====Other Modes of Transmission====
*In Europe, cases of ''B. burgdorferi'' sensu lato [[infected]] [[Tick|ticks]] are found predominantly in Norway, Netherlands, Germany, France, Italy, Slovenia and Poland, but have been isolated in almost every country on the continent. Lyme disease statistics for Europe can be found at [http://www.eurosurveillance.org/ew/2006/060622.asp Eurosurveillance website].
*While Lyme spirochetes have been found in insects other than ticks, reports of actual infectious transmission appear to be rare.<ref name="Magnarelli">{{cite journal | author=Magnarelli L, Anderson J | title=Ticks and biting insects infected with the etiologic agent of Lyme disease, ''Borrelia burgdorferi''. | journal=J Clin Microbiol | volume=26 | issue=8 | pages=1482-6 | year=1988 | pmid= 3170711 | url=http://www.pubmedcentral.gov/picrender.fcgi?artid=266646&blobtype=pdf | format=PDF}}</ref><ref name="Luger">{{cite journal | author=Luger S | title=Lyme disease transmitted by a biting fly. | journal=N Engl J Med | volume=322 | issue=24 | pages=1752 | year=1990 | pmid = 2342543 | url=http://cassia.org/library/N_Engl_J_Med_1990_Jun_14,322(24),1752.htm}}</ref>  
*''B. burgdorferi'' sensu lato infested ticks are being found more frequently in Japan, as well as in northwest China and far eastern Russia.<ref>{{cite journal |author=Li M, Masuzawa T, Takada N, ''et al'' |title=Lyme disease Borrelia species in northeastern China resemble those isolated from far eastern Russia and Japan |journal=Appl. Environ. Microbiol. |volume=64 |issue=7 |pages=2705-9 |year=1998 |pmid=9647853 |url=http://aem.asm.org/cgi/content/full/64/7/2705?view=long&pmid=9647853}}</ref><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 |url = http://www.nih.go.jp/JJID/57/229.html}}</ref> ''[[Borrelia]]'' has been isolated in Mongolia as well.<ref>{{cite journal |author=Walder G, Lkhamsuren E, Shagdar A, ''et al'' |title=Serological evidence for tick-borne encephalitis, borreliosis, and human granulocytic anaplasmosis in Mongolia |journal=Int. J. Med. Microbiol. |volume=296 Suppl 40 |issue= |pages=69-75 |year=2006 |pmid=16524782 |doi=10.1016/j.ijmm.2006.01.031}}</ref>
*[[Sexually transmitted infection|Sexual transmission]] have been reported; Lyme spirochetes have been found in semen and breast milk, however transmission of the spirochete by these routes is not known to occur.<ref name="Bach">{{cite conference | author=Bach G | title=Recovery of Lyme spirochetes by PCR in semen samples of previously diagnosed Lyme disease patients. | booktitle=14th International Scientific Conference on Lyme Disease | year=2001 | url=http://www.anapsid.org/lyme/bach.html}}</ref><ref name="Schmidt">{{cite journal | author=Schmidt B, Aberer E, Stockenhuber C, ''et al'' | title=Detection of ''Borrelia burgdorferi'' DNA by polymerase chain reaction in the urine and breast milk of patients with Lyme borreliosis. | journal=Diagn Microbiol Infect Dis | volume=21 | issue=3 | pages=121-8 | year=1995 | pmid = 7648832}}</ref><ref name="Steere_2003">{{cite web | author = Steere AC | title = Lyme Disease: Questions and Answers |publisher = Massachusetts General Hospital / Harvard Medical School | url = http://www.mgh.harvard.edu/medicine/rheu/Q&ALYME.pdf | format = PDF | date = 2003-02-01 | accessdate = 2007-03-22}}</ref>
*In South America tick-borne disease recognition and occurrence is rising.
*Congenital transmission of Lyme disease can occur from an infected mother to [[fetus]] through the [[placenta]] during pregnancy. However, prompt antibiotic treatment appears to prevent fetal harm.<ref>{{cite journal |author=Walsh CA, Mayer EW, Baxi LV |title=Lyme disease in pregnancy: case report and review of the literature |journal=Obstetrical & gynecological survey |volume=62 |issue=1 |pages=41-50 |year=2007 |pmid=17176487 |doi=10.1097/01.ogx.0000251024.43400.9a}}</ref>
*Ticks carrying ''B. burgdorferi'' sensu lato, as well as canine and human [[tick-borne disease]], have been reported widely in Brazil, but the subspecies of ''Borrelia'' has not yet been defined.<ref>{{cite journal |author=Mantovani E, Costa IP, Gauditano G, Bonoldi VL, Higuchi ML, Yoshinari NH |title=Description of Lyme disease-like syndrome in Brazil. Is it a new tick borne disease or Lyme disease variation? |journal=Braz. J. Med. Biol. Res. |volume=40 |issue=4 |pages=443-56 |year=2007 |pmid=17401487 }}</ref> The first reported case of Lyme disease in Brazil was made in 1993 in Sao Paulo.<ref>{{cite journal |author=Yoshinari NH, Oyafuso LK, Monteiro FG, ''et al'' |title=Lyme disease. Report of a case observed in Brazil |language=Portuguese |journal=Revista do Hospital das Clínicas |volume=48 |issue=4 |pages=170-4 |year=1993 |pmid=8284588 }}</ref> *''B. burgdorferi'' sensu stricto antigens in patients have been identified in Colombia and in Bolivia.  
*In Northern Africa ''B. burgdorferi'' sensu lato has been identified in Morocco, Algeria, Egypt and Tunisia.<ref>{{cite journal |author=Bouattour A, Ghorbel A, Chabchoub A, Postic D |title=Lyme borreliosis situation in North Africa |language=French |journal=Archives de l'Institut Pasteur de Tunis |volume=81 |issue=1-4 |pages=13-20 |year=2004 |pmid=16929760 }}</ref><ref>{{cite journal |author=Dsouli N, Younsi-Kabachii H, Postic D, ''et al'' |title=Reservoir role of lizard Psammodromus algirus in transmission cycle of Borrelia burgdorferi sensu lato (Spirochaetaceae) in Tunisia |journal=J. Med. Entomol. |volume=43 |issue=4 |pages=737-42 |year=2006 |pmid=16892633 }}</ref><ref>{{cite journal |author=Helmy N |title=Seasonal abundance of Ornithodoros (O.) savignyi and prevalence of infection with Borrelia spirochetes in Egypt |journal=Journal of the Egyptian Society of Parasitology |volume=30 |issue=2 |pages=607-19 |year=2000 |pmid=10946521}}</ref> 
*In Western and sub-Saharan Africa, tick-borne [[relapsing fever]] was first identified by the British physicians Joseph Dutton and John Todd in 1905.
*''Borrelia'' in the manifestation of Lyme disease in this region is presently unknown but evidence indicates that Lyme disease may occur in humans in sub-Saharan Africa. The abundance of hosts and tick vectors would favor the establishment of Lyme infection in Africa.<ref>{{cite journal |author=Fivaz BH, Petney TN |title=Lyme disease--a new disease in southern Africa? |journal=Journal of the South African Veterinary Association |volume=60 |issue=3 |pages=155-8 |year=1989 |pmid=2699499}}</ref> In East Africa, two cases of Lyme disease have been reported in Kenya.<ref>{{cite journal |author=Jowi JO, Gathua SN |title=Lyme disease: report of two cases |journal=East African medical journal |volume=82 |issue=5 |pages=267-9 |year=2005 |pmid=16119758}}</ref>
*In Australia there is no definitive evidence for the existence of ''B. burgdorferi'' or for any other [[Tick-borne disease|tick-borne]] [[Spirochaete|spirochete]] that may be responsible for a local syndrome being reported as Lyme disease.<ref>{{cite journal |author=Piesman J, Stone BF |title=Vector competence of the Australian paralysis tick, Ixodes holocyclus, for the Lyme disease spirochete Borrelia burgdorferi |journal=Int. J. Parasitol. |volume=21 |issue=1 |pages=109-11 |year=1991 |pmid=2040556}}</ref> 
*Cases of neuroborreliosis have been documented in Australia but are often ascribed to travel to other continents. The existence of Lyme disease in Australia is controversial.
*Data shows that Northern hemisphere temperate regions are most endemic for Lyme disease.<ref>{{cite journal |author=Grubhoffer L, Golovchenko M, Vancová M, Zacharovová-Slavícková K, Rudenko N, Oliver JH |title=Lyme borreliosis: insights into tick-/host-borrelia relations |journal=Folia Parasitol. |volume=52 |issue=4 |pages=279-94 |year=2005 |pmid=16405291}}</ref><ref>{{cite journal |author=Higgins R |title=Emerging or re-emerging bacterial zoonotic diseases: bartonellosis, leptospirosis, Lyme borreliosis, plague |journal=Rev. - Off. Int. Epizoot. |volume=23 |issue=2 |pages=569-81 |year=2004 |pmid=15702720}}</ref>


===Pathogenesis===
[[Image:Geographical distribution of reported Lyme Disease cases.png|centre|650px|Geographical distribution of Lyme disease.]]
* ''B. burgdorferi'' has been shown to invade a variety of cells, including:
**[[Endothelium]]<ref name="Ma-b">{{cite journal | author=Ma Y, Sturrock A, Weis JJ | title=Intracellular localization of Borrelia burgdorferi within human endothelial cells | journal=Infect Immun | year=1991 | pages=671-8 | volume=59 | issue=2 | pmid= 1987083 | url=http://www.pubmedcentral.gov/picrender.fcgi?artid=257809&blobtype=pdf | format=PDF}}</ref
<nowiki>[[Fibroblasts]]</nowiki><nowiki><ref name="Klempner-b"></nowiki>{{cite journal | author=Klempner MS, Noring R, Rogers RA | title=Invasion of human skin fibroblasts by the Lyme disease spirochete, Borrelia burgdorferi | journal=J Infect Dis | year=1993 | pages=1074-81 | volume=167 | issue=5 | pmid= 8486939}}</ref>
**[[Lymphocytes]]<ref name="Dorward">{{cite journal | author=Dorward DW, Fischer ER, Brooks DM | title=Invasion and cytopathic killing of human lymphocytes by spirochetes causing Lyme disease | journal=Clin Infect Dis | year=1997 | pages=S2-8 | volume=25 Suppl 1 | pmid= 9233657}}</ref>
**[[Macrophages]]<ref name="Montgomery">{{cite journal | author=Montgomery RR, Nathanson MH, Malawista SE | title=The fate of Borrelia burgdorferi, the agent for Lyme disease, in mouse macrophages. Destruction, survival, recovery | journal=J Immunol | year=1993 | pages=909-15 | volume=150 | issue=3 | pmid= 8423346}}</ref>
**[[Keratinocytes]]<ref name="Aberer">{{cite journal | author=Aberer E, Kersten A, Klade H, Poitschek C, Jurecka W | title=Heterogeneity of Borrelia burgdorferi in the skin | journal=Am J Dermatopathol | year=1996 | pages=571-9 | volume=18 | issue=6 | pmid= 8989928}}</ref>
**[[Synovium]]<ref name="Girschick">{{cite journal | author=Girschick HJ, Huppertz HI, Russmann H, Krenn V, Karch H | title=Intracellular persistence of Borrelia burgdorferi in human synovial cells | journal=Rheumatol Int | year=1996 | pages=125-32 | volume=16 | issue=3 | pmid= 8893378}}</ref><ref name="Nanagara">{{cite journal | author=Nanagara R, Duray PH, Schumacher HR Jr | title=Ultrastructural demonstration of spirochetal antigens in synovial fluid and synovial membrane in chronic Lyme disease: possible factors contributing to persistence of organisms | journal=Hum Pathol | year=1996 | pages=1025-34 | volume=27 | issue=10 | pmid= 8892586}}</ref>
**[[Neuronal]] and [[glial cells]]<ref name="Livengood">{{cite journal | author=Livengood JA, Gilmore RD | title = Invasion of human neuronal and glial cells by an infectious strain of Borrelia burgdorferi. | journal = Microbes Infect | volume = [Epub ahead of print] | year=2006 | id = PMID 17045505}}</ref>
* By 'hiding' inside these cells, ''B. burgdorferi'' is able to evade the immune system and is protected to varying degrees against antibiotics, allowing the infection to persist.<ref name="Georgilis">{{cite journal | author=Georgilis K, Peacocke M, Klempner MS | title=Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone ''in vitro'' | journal=J Infect Dis | year=1992 | pages=440-4 | volume=166 | issue=2 | pmid= 1634816}}</ref><ref name="Brouqui">{{cite journal | author=Brouqui P, Badiaga S, Raoult D | title=Eucaryotic cells protect Borrelia burgdorferi from the action of penicillin and ceftriaxone but not from the action of doxycycline and erythromycin | journal=Antimicrob Agents Chemother | year=1996 | pages=1552-4 | volume=40 | issue=6 | pmid= 8726038 | url=http://aac.asm.org/cgi/reprint/40/6/1552.pdf | format=PDF}}</ref>
*''B. burgdorferi'' altered [[morphology (biology)|morphological]] forms, i.e. [[spheroplast]]s (cysts, granules). The existence of ''B. burgdorferi'' spheroplasts, which lack a [[cell wall]], has been documented in the following models:
**[[In vitro]] model<ref name="Alban">{{cite journal | author=Alban PS, Johnson PW, Nelson DR | title=Serum-starvation-induced changes in protein synthesis and morphology of Borrelia burgdorferi | journal=Microbiology | year=2000 | pages=119-27 | volume=146 ( Pt 1) | pmid= 10658658 | url =http://mic.sgmjournals.org/cgi/content/full/146/1/119}}</ref><ref name="Mursic">{{cite journal | author=Mursic VP, Wanner G, Reinhardt S, ''et al'' | title=Formation and cultivation of Borrelia burgdorferi spheroplast-L-form variants | journal=Infection | year=1996 | pages=218-26 | volume=24 | issue=3 | pmid= 8811359}}</ref><ref name="Kersten">{{cite journal | author=Kersten A, Poitschek C, Rauch S, Aberer E | title=Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi | journal=Antimicrob Agents Chemother | year=1995 | pages=1127-33 | volume=39 | issue=5 | pmid= 7625800 | url=http://aac.asm.org/cgi/reprint/39/5/1127.pdf | format=PDF}}</ref><ref name="Schaller">{{cite journal | author=Schaller M, Neubert U | title=Ultrastructure of Borrelia burgdorferi after exposure to benzylpenicillin | journal=Infection | year=1994 | pages=401-6 | volume=22 | issue=6 | pmid= 7698837}}</ref>
**[[In vivo]] model<ref name="Nanagara" /><ref name="Mursic" /><ref name="Phillips-c">{{cite journal | author=Phillips SE, Mattman LH, Hulinska D, Moayad H | title=A proposal for the reliable culture of Borrelia burgdorferi from patients with chronic Lyme disease, even from those previously aggressively treated | journal=Infection | year=1998 | pages=364-7 | volume=26 | issue=6 | pmid= 9861561 | url=http://www.cbc.ca/ideas/features/Aids/phillips.html}}</ref>
**[[Ex vivo]] model.<ref name="Duray">{{cite journal | author=Duray PH, Yin SR, Ito Y, ''et al'' | title=Invasion of human tissue ex vivo by Borrelia burgdorferi | journal=J Infect Dis | year=2005 | pages=1747-54 | volume=191 | issue=10 | pmid= 15838803}}</ref>
* The fact that energy is required for the spiral bacterium to convert to the cystic form suggests that these altered forms have a survival function, and are not merely end stage degeneration products.<ref name="Alban" />
* The spheroplasts are indeed [[virulent]] and [[infectious]], able to survive under adverse environmental conditions, and have been shown to revert back to the spiral form in vitro, once conditions are more favorable.<ref name="Gruntar">{{cite journal | author=Gruntar I, Malovrh T, Murgia R, Cinco M | title=Conversion of Borrelia garinii cystic forms to motile spirochetes ''in vivo'' | journal=APMIS | year=2001 | pages=383-8 | volume=109 | issue=5 | pmid= 11478686}}</ref><ref name="Murgia">{{cite journal | author=Murgia R, Cinco M | title=Induction of cystic forms by different stress conditions in Borrelia burgdorferi | journal=APMIS | year=2004 | pages=57-62 | volume=112 | issue=1 | pmid= 14961976}}</ref>


* A number of other factors make ''B. burgdorferi'' [[spheroplast]]s a key factor in the relapsing, persistant nature of Lyme disease. 
<br clear="left" />
* Compared to the spiral form, spheroplasts have dramatically reduced surface area for immune surveillance. 
* They also express different surface proteins; another reason for [[seronegative]] disease (i.e. [[Type I and type II errors|false-negative]] antibody tests), as current tests only look for antibodies to surface proteins of the ''spiral'' form. 
* In addition, ''B. burgdorferi'' spheroplasts are generally not susceptible to the [[antibiotics]] traditionally used for Lyme disease. They have instead shown sensitivity in vitro to [[Human parasitic diseases|antiparasitic]] drugs  to which the spiral form of ''B. burgdorferi'' is not sensitive. Drugs such as:
**[[Metronidazole]], <ref name="Brorson-c">{{cite journal | author=Brorson O, Brorson SH | title=An ''in vitro'' study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to metronidazole | journal=APMIS | year=1999 | pages=566-76 | volume=107 | issue=6 | pmid= 10379684}}</ref>
**[[tinidazole]]<ref name="Brorson-d">{{cite journal | author=Brorson O, Brorson SH | title=An ''in vitro'' study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to tinidazole | journal=Int Microbiol | year=2004 | pages=139-42 | volume=7 | issue=2 | pmid= 15248163 | url=http://www.im.microbios.org/26June04/09%20Brorson.pdf | format=PDF}}</ref>
**[[hydroxychloroquine]]<ref name="Brorson-e">{{cite journal | author=Brorson O, Brorson SH | title=An ''in vitro'' study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine | journal=Int Microbiol | year=2002 | pages=25-31 | volume=5 | issue=1 | pmid= 12102233}}</ref>  


====Mechanisms of persistence====
===Age and Gender===
*Like the Borrelia that cause [[relapsing fever]], ''B. burgdorferi'' has the ability to vary its surface proteins in response to [[immune system|immune]] attack.<ref name="pmid15065567">{{cite journal| author=Embers ME, Ramamoorthy R, Philipp MT| title=Survival strategies of Borrelia burgdorferi, the etiologic agent of Lyme disease. | journal=Microbes Infect | year= 2004 | volume= 6 | issue= 3 | pages= 312-8 | pmid=15065567 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15065567  }} </ref><ref name="Liang">{{cite journal | author=Liang FT, Yan J, Mbow ML, ''et al'' | title=Borrelia burgdorferi changes its surface antigenic expression in response to host immune responses | journal=Infect Immun | year=2004 | pages=5759-67 | volume=72 | issue=10 | pmid= 15385475 | url=http://iai.asm.org/cgi/content/full/72/10/5759 }}</ref>
*There's a higher incidence of [[infection]] among children and infants of less than a year to 15 years.  
* This ability is related to the genomic complexity of ''B. burgdorferi'', and is another way ''B. burgdorferi'' evades the immune system to establish a presistant infection.<ref>{{cite journal |author=Gilmore RD, Howison RR, Schmit VL, ''et al'' |title=Temporal expression analysis of the Borrelia burgdorferi paralogous gene family 54 genes BBA64, BBA65, and BBA66 during persistent infection in mice |journal=Infect. Immun. |volume=75 |issue=6 |pages=2753-64 |year=2007 |pmid=17371862 |doi=10.1128/IAI.00037-07}}</ref>
*Another peak occurs in individuals between the ages of 40 to 55 years.  
*While ''B. burgdorferi'' is susceptible to a number of [[antibiotics]] [[in vitro]], there are contradictory reports as to the efficacy of antibiotics [[in vivo]]. ''B. burgdorferi'' may persist in humans and animals for months or years despite a robust immune response and standard antibiotic treatment, particularly when treatment is delayed and dissemination widespread. Numerous studies have demonstrated persistence of infection despite antibiotic therapy.<ref name="Bayer">{{cite journal | author=Bayer ME, Zhang L, Bayer MH | title=Borrelia burgdorferi DNA in the urine of treated patients with chronic Lyme disease symptoms. A PCR study of 97 cases | journal=Infection | year=1996 | pages=347-53 | volume=24 | issue=5 | pmid= 8923044}}</ref><ref name="Preac-Mursic">{{cite journal | author=Preac-Mursic V, Weber K, Pfister HW, ''et al'' | title=Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis | journal=Infection | year=1989 | pages=355-9 | volume=17 | issue=6 | pmid= 2613324}}</ref><ref name="Oksi-c">{{cite journal | author=Oksi J, Marjamaki M, Nikoskelainen J, Viljanen MK | title=Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis | journal=Ann Med | year=1999 | pages=225-32 | volume=31 | issue=3 | pmid= 10442678}}</ref>
*On average, there is a higher incidence among males than females. However among ages 70 and higher, females tend to have a higher incidence of infection.  
*Various survival strategies of ''B. burgdorferi'' have been posted to explain this phenomenon, including the following:<ref name="pmid15065567" />
[[Image:Agesex lyme.gif|center|400px|thumb|Peaks occur in males between the ages of less than one year to 15 and 40 to 55 years. Female patients are at a slightly higher risk than male patients above the age of 70.]]
**Physical Sequestration
***Physical sequestration of ''B. burgdorferi'' in sites that are inaccessible to the immune system and antibiotics, such as the [[brain]] and [[central nervous system]].<ref name="Miklossy">{{cite journal | author=Miklossy J, Khalili K, Gern L, ''et al'' | title=Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease | journal=J Alzheimers Dis | year=2004 | pages=639-49; discussion 673-81 | volume=6 | issue=6 | pmid= 15665404}}</ref>
***New evidence suggests that ''B. burgdorferi'' may use the host's [[fibrinolytic]] system to penetrate the [[blood-brain barrier]].<ref name="Grab">{{cite journal | author=Grab DJ, Perides G, Dumler JS, Kim KJ, Park J, Kim YV, Nikolskaia O, Choi KS, Stins MF, Kim KS | title=Borrelia burgdorferi, host-derived proteases, and the blood-brain barrier | journal=Infect Immun | year=2005 | pages=1014-22 | volume=73 | issue=2 | pmid= 15664945 | url=http://iai.asm.org/cgi/content/full/73/2/1014}}</ref>
**[[Immune system]] suppression
***[[Complement system|Complement]] inhibition, induction of anti-inflammatory [[cytokines]] such as [[Interleukin 10|IL-10]], and the formation of [[immune complex]]es have all been documented in ''B. burgdorferi'' infection.<ref name="pmid15065567" />
***Furthermore, the existence of immune complexes provides another explanation for [[seronegative]] disease (i.e. [[Type I and type II errors|false-negative]] antibody tests of [[blood]] and [[cerebrospinal fluid]]), as studies have shown that substantial numbers of seronegative Lyme patients have antibodies bound up in these complexes.<ref name="Schutzer">{{cite journal | author=Schutzer SE, Coyle PK, Reid P, Holland B | title=Borrelia burgdorferi-specific immune complexes in acute Lyme disease | journal=JAMA | year=1999 | pages=1942-6 | volume=282 | issue=20 | pmid= 10580460}}</ref>


==References==
==References==
{{reflist|2}}
{{Reflist|2}}


[[Category:Bacterial diseases]]
[[Category:Bacterial diseases]]

Revision as of 14:40, 28 July 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Overview

Lyme disease is the most common tick borne disease in North America and the the ratio of Lyme disease infection is 7.9 cases for every 100,000 persons. The number of people diagnosed with Lyme disease each year in the United States is around 300,000. This disease is concentrated heavily in the northeast and upper mid-west.

Epidemiology and Demographics

Prevalence

Incidence

  • Lyme disease is the most common tick-borne disease in North America and Europe, and one of the fastest-growing infectious diseases in the United States.
  • Of cases reported to the United States Center for Disease Control (CDC), the ratio of Lyme disease infection is 7.9 cases for every 100,000 persons.
  • In the ten states where Lyme disease is most common, the average was 31.6 cases for every 100,000 persons for the year 2005.[1]
  • Although Lyme disease has now been reported in 49 of 50 states in the U.S, about 99% of all reported cases are confined to just five geographic areas including New England, Mid-Atlantic, East-North Central, South Atlantic, and West North-Central.
Reported cases of Lyme disease in the United Stated from 2001 to 2015

Widespread disease and endemic regions

  • The number of reported cases of the disease have been increasing, as are endemic regions in North America.
  • B. burgdorferi sensu lato has been maintained in enzootic cycles in California as well as other regions throughout North America, Europe and North Africa. Indeed, the DNA of Borrelia has been detected in lizards, indicating that they can be infected.[2]
  • In Europe, cases of B. burgdorferi sensu lato infected ticks are found predominantly in Norway, Netherlands, Germany, France, Italy, Slovenia and Poland, but have been isolated in almost every country on the continent. Lyme disease statistics for Europe can be found at Eurosurveillance website.
  • B. burgdorferi sensu lato infested ticks are being found more frequently in Japan, as well as in northwest China and far eastern Russia.[3][4] Borrelia has been isolated in Mongolia as well.[5]
  • In South America tick-borne disease recognition and occurrence is rising.
  • Ticks carrying B. burgdorferi sensu lato, as well as canine and human tick-borne disease, have been reported widely in Brazil, but the subspecies of Borrelia has not yet been defined.[6] The first reported case of Lyme disease in Brazil was made in 1993 in Sao Paulo.[7] *B. burgdorferi sensu stricto antigens in patients have been identified in Colombia and in Bolivia.
  • In Northern Africa B. burgdorferi sensu lato has been identified in Morocco, Algeria, Egypt and Tunisia.[8][9][10]
  • In Western and sub-Saharan Africa, tick-borne relapsing fever was first identified by the British physicians Joseph Dutton and John Todd in 1905.
  • Borrelia in the manifestation of Lyme disease in this region is presently unknown but evidence indicates that Lyme disease may occur in humans in sub-Saharan Africa. The abundance of hosts and tick vectors would favor the establishment of Lyme infection in Africa.[11] In East Africa, two cases of Lyme disease have been reported in Kenya.[12]
  • In Australia there is no definitive evidence for the existence of B. burgdorferi or for any other tick-borne spirochete that may be responsible for a local syndrome being reported as Lyme disease.[13]
  • Cases of neuroborreliosis have been documented in Australia but are often ascribed to travel to other continents. The existence of Lyme disease in Australia is controversial.
  • Data shows that Northern hemisphere temperate regions are most endemic for Lyme disease.[14][15]
Geographical distribution of Lyme disease.
Geographical distribution of Lyme disease.


Age and Gender

  • There's a higher incidence of infection among children and infants of less than a year to 15 years.
  • Another peak occurs in individuals between the ages of 40 to 55 years.
  • On average, there is a higher incidence among males than females. However among ages 70 and higher, females tend to have a higher incidence of infection.
Peaks occur in males between the ages of less than one year to 15 and 40 to 55 years. Female patients are at a slightly higher risk than male patients above the age of 70.

References

  1. CDC (2006-10-02). "Reported Cases of Lyme Disease by Year, United States, 1991-2005". Retrieved 2007-08-20.
  2. Swanson KI, Norris DE (2007). "Detection of Borrelia burgdorferi DNA in lizards from Southern Maryland". Vector Borne Zoonotic Dis. 7 (1): 42–9. doi:10.1089/vbz.2006.0548. PMID 17417956.
  3. Li M, Masuzawa T, Takada N; et al. (1998). "Lyme disease Borrelia species in northeastern China resemble those isolated from far eastern Russia and Japan". Appl. Environ. Microbiol. 64 (7): 2705–9. PMID 9647853.
  4. Masuzawa T (2004). "Terrestrial distribution of the Lyme borreliosis agent Borrelia burgdorferi sensu lato in East Asia". Jpn. J. Infect. Dis. 57 (6): 229–35. PMID 15623946.
  5. Walder G, Lkhamsuren E, Shagdar A; et al. (2006). "Serological evidence for tick-borne encephalitis, borreliosis, and human granulocytic anaplasmosis in Mongolia". Int. J. Med. Microbiol. 296 Suppl 40: 69–75. doi:10.1016/j.ijmm.2006.01.031. PMID 16524782.
  6. Mantovani E, Costa IP, Gauditano G, Bonoldi VL, Higuchi ML, Yoshinari NH (2007). "Description of Lyme disease-like syndrome in Brazil. Is it a new tick borne disease or Lyme disease variation?". Braz. J. Med. Biol. Res. 40 (4): 443–56. PMID 17401487.
  7. Yoshinari NH, Oyafuso LK, Monteiro FG; et al. (1993). "Lyme disease. Report of a case observed in Brazil". Revista do Hospital das Clínicas (in Portuguese). 48 (4): 170–4. PMID 8284588.
  8. Bouattour A, Ghorbel A, Chabchoub A, Postic D (2004). "Lyme borreliosis situation in North Africa". Archives de l'Institut Pasteur de Tunis (in French). 81 (1–4): 13–20. PMID 16929760.
  9. Dsouli N, Younsi-Kabachii H, Postic D; et al. (2006). "Reservoir role of lizard Psammodromus algirus in transmission cycle of Borrelia burgdorferi sensu lato (Spirochaetaceae) in Tunisia". J. Med. Entomol. 43 (4): 737–42. PMID 16892633.
  10. Helmy N (2000). "Seasonal abundance of Ornithodoros (O.) savignyi and prevalence of infection with Borrelia spirochetes in Egypt". Journal of the Egyptian Society of Parasitology. 30 (2): 607–19. PMID 10946521.
  11. Fivaz BH, Petney TN (1989). "Lyme disease--a new disease in southern Africa?". Journal of the South African Veterinary Association. 60 (3): 155–8. PMID 2699499.
  12. Jowi JO, Gathua SN (2005). "Lyme disease: report of two cases". East African medical journal. 82 (5): 267–9. PMID 16119758.
  13. Piesman J, Stone BF (1991). "Vector competence of the Australian paralysis tick, Ixodes holocyclus, for the Lyme disease spirochete Borrelia burgdorferi". Int. J. Parasitol. 21 (1): 109–11. PMID 2040556.
  14. Grubhoffer L, Golovchenko M, Vancová M, Zacharovová-Slavícková K, Rudenko N, Oliver JH (2005). "Lyme borreliosis: insights into tick-/host-borrelia relations". Folia Parasitol. 52 (4): 279–94. PMID 16405291.
  15. Higgins R (2004). "Emerging or re-emerging bacterial zoonotic diseases: bartonellosis, leptospirosis, Lyme borreliosis, plague". Rev. - Off. Int. Epizoot. 23 (2): 569–81. PMID 15702720.


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