Borrelia burgdorferi: Difference between revisions

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{{SI}}
{{Lyme disease}}
{{About0|Lyme disease}}
{{About0|Lyme disease}}
{{CMG}}; {{AE}} {{RT}}
{{CMG}}; {{AE}} {{RT}}, {{IMD}}
{{Seealso|Borrelia}}
{{Seealso|Borrelia}}
{{Seealso|Borrelia mayonii}} (a newly discovered ''Borrelia'' species that has been associated with Lyme disease)
{{Main|Lyme disease microbiology}}
{{Main|Lyme disease microbiology}}


==Overview==
==Overview==
'''''Borrelia burgdorferi''''' is species of [[bacteria]] of the [[Spirochaete|spirochete]] class of the [[genus]] ''[[Borrelia]]''. ''B. burgdorferi'' is predominant in North America, but also exists in Europe, and is the agent of [[Lyme disease]].
[[Borrelia burgdorferi]] is species of [[bacteria]] of the [[Spirochaete|spirochete]] class of the [[genus]] ''[[Borrelia]]''. ''[[B. burgdorferi]]'' is predominant in North America, but also exists in Europe, and is the causative agent of [[Lyme disease]].
It is a [[Zoonosis|zoonotic]], [[vector (biology)|vector-borne disease]] transmitted by [[ticks]] and is named after the researcher [[Willy Burgdorfer]] who first isolated the [[bacterium]] in 1982. ''[[B. burgdorferi]]'' is one of the few [[pathogenic]] [[bacteria]] that can survive without [[iron]], having replaced all of its iron-sulphur cluster [[enzymes]] with [[enzymes]] that use [[manganese]], thus avoiding the problem many [[pathogenic bacteria]] face in acquiring [[iron]].
[[B. burgdorferi]] infections have been linked to [[non-Hodgkin lymphoma]]s.<ref name="Guidoboni_2006">{{cite journal |author=Guidoboni M, Ferreri AJ, Ponzoni M, Doglioni C, Dolcetti R |title=Infectious agents in mucosa-associated lymphoid tissue-type lymphomas: pathogenic role and therapeutic perspectives |journal=Clinical lymphoma & myeloma |volume=6 |issue=4 |pages=289-300 |year=2006 |pmid=16507206}}</ref>


It is a [[Zoonosis|zoonotic]], [[vector (biology)|vector-borne disease]] transmitted by [[ticks]] and is named after the researcher [[Willy Burgdorfer]] who first isolated the bacterium in 1982. ''B. burgdorferi'' is one of the few pathogenic bacteria that can survive without iron, having replaced all of its iron-sulphur cluster enzymes with enzymes that use manganese, thus avoiding the problem many pathogenic bacteria face in acquiring iron.
==Organism==
[[Image:Borrelia image.jpg|thumb|left|''Borrelia burgdorferi'' the causative agent of Lyme disease (borreliosis). Magnified 400 times. - [https://phil.cdc.gov/phil/details.asp?pid=6631 Source: Public Health Image Library]]]
*'''[[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 disease|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 complex.  


''B. burgdorferi'' infections have been linked to [[non-Hodgkin lymphoma]]s.<ref name=Guidoboni_2006>{{cite journal |author=Guidoboni M, Ferreri AJ, Ponzoni M, Doglioni C, Dolcetti R |title=Infectious agents in mucosa-associated lymphoid tissue-type lymphomas: pathogenic role and therapeutic perspectives |journal=Clinical lymphoma & myeloma |volume=6 |issue=4 |pages=289-300 |year=2006 |pmid=16507206}}</ref>
*''Borrelia'' are [[Microaerophile|microaerophillic]] and slow-growing&mdash;the primary reason for the long delays when diagnosing Lyme disease&mdash;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 [[Strain (biology)|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>


==Gallery==
*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>
 
*On February 2016, a second, a new organism, ''[[B. mayonii]]'', has been reported for causing [[Lyme disease]] (''see B. mayonii [[Borrelia mayonii|here]]'').
:*''[[Borrelia mayonii]]'' causes similar symptoms to ''[[Borrelia burgdorferi]]''.
:*However, unlike ''[[B. burgdorferi]],'' ''[[B. mayonii]]'' may induce a quick onset of [[nausea and vomiting]].
:*The rash associated with this new organism is also different from the conventional, bulls-eye [[rash]]. The [[rash]] associated with ''[[Borrelia mayonii|B. mayonii]]'' has been reported as a diffuse [[rash]], covering the entire body in "red spots."<ref>CBS News Lyme Disease. http://www.cbsnews.com/news/lyme-disease-just-got-nastier/ Accessed February 9, 2016. </ref>
 
<br style="clear:left" />
 
==Structure and growth==
''[[B. burgdorferi]]'' is a highly specialized, motile, two-[[membrane]], spiral-shaped [[spirochete]] ranging from about 9 to 32 [[1 E-6 m|micrometers]] in length. It is often described as [[gram-negative]] and has an outer membrane with [[lipopolysaccharide]] (LPS), though it stains only weakly in the [[Gram stain]]. ''[[B. burgdorferi]]'' is a [[microaerophilic]] organism, requiring little [[oxygen]] to survive. It lives primarily as an [[extracellular]] [[pathogen]], although it can also hide [[intracellular]]ly (see [[Lyme disease pathophysiology|Mechanisms of persistence]] section).
 
Like other [[Spirochaete|spirochetes]] such as [[T. pallidum]] (the agent of [[syphilis]]), ''[[B. burgdorferi]]'' has an axial filament composed of [[flagella]] which run lengthways between its [[cell wall]] and [[outer membrane]]. This structure allows the [[Spirochaete|spirochete]] to move efficiently in corkscrew fashion through [[viscous]] media, such as [[connective tissue]]. As a result, ''[[B. burgdorferi]]'' can [[Disseminated disease|disseminate]] throughout the body within days to weeks of [[infection]], penetrating deeply into [[Tissue (biology)|tissue]] where the [[immune system]] and [[antibiotics]] may not be able to eradicate the [[infection]].
 
''[[B. burgdorferi]]'' is very slow growing, with a [[doubling time]] of 12-18 hours<ref>Kelly, R. T. (1984). Genus IV. Borrelia Swellengrebel 1907, 582AL. In Bergey's Manual of Systematic Bacteriology, vol. 1, pp. 57–62. Edited by N. R. Krieg & J. G. Holt. Baltimore: Williams & Wilkins.</ref> (in contrast to pathogens such as [[Streptococcus]] and [[Staphylococcus]], which have a doubling time of 20-30 minutes). Since most [[antibiotics]] kill [[bacteria]] only when they are dividing, this longer [[doubling time]] necessitates the use of relatively longer treatment courses for [[Lyme disease]]. [[Antibiotics]] are most effective during the [[bacterial growth|growth phase]], which for ''[[B. burgdorferi]]'' occurs in four-week cycles.
 
==Outer surface proteins==
The [[outer membrane]] of [[Borrelia burgdorferi]] is composed of various unique outer surface [[lipoproteins|proteins]] (Osp) that have been characterized (OspA through OspF). They are presumed to play a role in [[virulence]].
 
OspA and OspB are by far the most abundant outer surface [[Protein|proteins]].
 
The OspA and OspB [[Gene|genes]] encode the major [[outer membrane]] proteins of the [[B. burgdorferi]]. The two Osp [[Protein|proteins]] show a high degree of [[Sequence (biology)|sequence]] similarity, indicating a recent evolutionary event. [[Molecular]] [[analysis]] and [[Sequence (biology)|sequence]] comparison of OspA and OspB with other proteins has revealed similarity to the signal [[peptides]] of [[prokaryotic]] [[lipoproteins]].<ref>Bergstrom S. , Bundoc V.G. , Barbour A.G. Molecular analysis of linear plasmid-encoded major surface proteins, OspA and OspB, of the Lyme disease spirochaete Borrelia burgdorferi. Mol. Microbiol. 3 479-486 1989</ref>Virtually all [[spirochetes]] in the [[midgut]] of an unfed nymph [[tick]] express OspA.
 
OspC is an [[antigen]]-detection of its presence by the host organism and can stimulate an [[immune response]]. While each individual [[Bacteria|bacterial]] cell contains just one copy of the [[gene]] encoding OspC, populations of ''[[B. burgdorferi]]'' have shown high levels of variation among individuals in the [[gene]] [[Sequence (biology)|sequence]] for OspC.<ref>Girschick, J. and Singh, S.E. Molecular survival strategies of the lyme disease spirochete Borrelia burgdorferi. Sep, 2004. The Lancet Infectious Diseases: Volume 4, Issue 9, September 2004, Pages 575-583.</ref> OspC is likely to play a role in [[Transmission (medicine)|transmission]] from [[vector]] to [[Host (biology)|host]], since it has been observed that the [[protein]] is only expressed in the presence of [[mammalian]] [[blood]] or [[Tissue (biology)|tissue]].<ref name="Fikrig">Fikrig, E. and Pal, U. Adaptation of Borrelia burgdorferi in the vector and vertebrate host. Microbes and Infection Volume 5, Issue 7, June 2003, Pages 659-666. PMID 12787742</ref>
 
The functions of OspD are unknown.
 
OspE and OspF are structurally arranged in tandem as one [[Transcription|transcriptional]] unit under the control of a common [[Promoter region|promoter]].<ref>Lam TT, Nguyen TP, Montgomery RR, Kantor FS, Fikrig E, Flavell RA. Outer surface proteins E and F of Borrelia burgdorferi, the agent of Lyme disease. Infect Immun. 1994 Jan;62(1):290-8.</ref>
In [[Transmission (medicine)|transmission]] to the [[mammalian]] [[Host (biology)|host]], when the nymphal [[tick]] begins to feed, and the [[spirochetes]] in the [[midgut]] begin to multiply rapidly, most [[Spirochaete|spirochetes]] cease expressing OspA on their surface. Simultaneous with the disappearance of OspA, the [[Spirochetes|spirochete]] [[population]] in the [[midgut]] begins to express a OspC. [[Upregulation]] of OspC begins during the first day of feeding and peaks 48 hours after attachment.<ref>Schwan TG, Piesman J.  Temporal changes in outer surface proteins A and C of the Lyme disease-associated spirochete, Borrelia burgdorferi, during the chain of infection in ticks and mice. J Clin Microbiol 2000;38:382-8.</ref>
 
==General Tick Life Cycle==
[[Image:Lifecycle.jpg|left|thumb| This image displays an example of the tick lifecycle, based on stages and the months that they are most likely to occur during. - Source: https://www.nih.gov]]A [[Ticks|tick's]] life cycle is composed of four stages: hatching (egg), ''nymph'' (six legged), nymph (eight legged), and an adult.
 
[[Ticks]] require [[blood]] meal to survive through their [[life cycle]].
 
[[Host (biology)|Hosts]] for [[tick]] [[blood]] meals include [[mammals]], [[birds]], [[reptiles]], and amphibians. [[Ticks]] will most likely transfer between different [[Host (biology)|hosts]] during the different stages of their [[life cycle]].
 
Humans are most often targeted during the nymph and adult stages of the [[life cycle]].
 
[[Life cycle]] is also dependent on seasonal variation.
 
Ticks will go from eggs to larva during the summer months, infecting [[Birds|bird]] or [[rodent]] host during the larval stage.
 
Larva will [[Infection|infect]] the host from the summer until the following spring, at which point they will progress into the nymph stage.
 
During the nymph stage, a tick will most likely seek a [[Mammals|mammal]] [[Host (biology)|host]] (including humans).
 
A nymph will remain with the selected host until the following fall at which point it will progress into an adult.
 
As an adult, a [[tick]] will feed on a [[mammalian]] [[Host (biology)|host]]. However unlike previous stages, [[ticks]] will prefer larger [[mammals]] over [[Rodent|rodents]].
 
The average [[tick]] [[life cycle]] requires three years for completion.
 
Different species will undergo certain variations within their individual [[Life cycle|life cycles]]. <ref name="LCT CDC”">Life Cycle of Ticks that Bite Humans (2015).  http://www.cdc.gov/ticks/life_cycle_and_hosts.html Accessed on December 30, 2015</ref>
 
==''Borrelia burgdoferi'' lifecycle==
The [[life-cycle]] concept encompassing reservoirs and [[Infection|infections]] in multiple [[Host (biology)|hosts]] has recently been expanded to encompass forms of the [[Spirochaete|spirochete]] which differ from the motile corkscrew form, and these include cystic forms [[spheroplast|spheroplast-like]], straighted non-coiled bacillary forms which are immotile [[flagellin|due to flagellin mutations]] and granular forms [[Coccus|coccoid in profile]]. The model of [[Plasmodium]] species [[Malaria]] with multiple [[parasitic]] profiles demonstrable in various host insects and mammals is a hypothesized model for a similarly complex proposed [[Borrelia]] [[spirochete]] life cycle.
<ref>Macdonald AB. "A life cycle for Borrelia spirochetes?" Med Hypotheses. 2006;67(4):810-8. PMID 16716532</ref>
<ref>[http://www.lymeinfo.net/medical/LDAdverseConditions.pdf Lymeinfo.net - LDAdverseConditions]</ref>
 
Whereas [[B. burgdorferi]] is most associated with [[deer tick]] and the white footed mouse,<ref>Wallis RC, Brown SE, Kloter KO, Main AJ Jr.  Erythema chronicum migrans and lyme arthritis: field study of ticks. Am J Epidemiol. 1978 Oct;108(4):322-7.PMID 727201</ref> [[B. afzelii]] is most frequently detected in [[rodent]]-feeding [[vector]] [[Tick|ticks]], B. garinii and B. valaisiana appear to be associated with [[birds]]. Both [[Rodent|rodents]] and [[birds]] are competent reservoir hosts for [[Borrelia burgdorferi]] sensu stricto. The resistance of a genospecies of [[Lyme disease]] [[Spirochaete|spirochetes]] to the bacteriolytic activities of the alternative [[immune]] [[complement]] pathway of various host [[species]] may determine its reservoir [[Host (biology)|host]] association.
 
===Ecology===
Urbanization and other anthropogenic factors can be implicated in the spread of the [[Lyme disease]] into the human population. In many areas, expansion of suburban neighborhoods has led to the gradual deforestation of surrounding wooded areas and increasing "border" contact between humans and [[tick]]-dense areas. Human expansion has also resulted in a gradual reduction of the predators that normally hunt deer as well as mice, chipmunks and other small [[Rodent|rodents]] -- the primary reservoirs for [[Lyme disease]]. As a consequence of increased human contact with [[Host (biology)|host]] and [[vector]], the likelihood of [[Transmission (medicine)|transmission]] of [[Lyme disease|Lyme]] to residents of [[Endemic (epidemiology)|endemic]] area has greatly increased.<ref name="LoGiudice">{{cite journal | author = LoGiudice K, Ostfeld R, Schmidt K, Keesing F | title = The ecology of infectious disease: effects of host diversity and community composition on Lyme disease risk. | journal = Proc Natl Acad Sci U S A | volume = 100 | issue = 2 | pages = 567-71 | year = 2003 | pmid = 12525705}}</ref><ref name="Patz">{{cite journal | author = Patz J, Daszak P, Tabor G, ''et al'' | title = Unhealthy landscapes: Policy recommendations on land use change and infectious disease emergence. | journal = Environ Health Perspect | volume = 112 | issue = 10 | pages = 1092-8 | year = 2004 | pmid = 15238283}}</ref> Researchers are also investigating possible links between global warming and the spread of [[vector]]-borne diseases including [[Lyme disease]].<ref name="Khasnis">{{cite journal |author=Khasnis AA, Nettleman MD |title=Global warming and infectious disease |journal=Arch. Med. Res. |volume=36 |issue=6 |pages=689-96 |year=2005 |pmid=16216650 |doi=10.1016/j.arcmed.2005.03.041}}</ref>
 
The [[deer tick]] (''[[Ixodes scapularis]]'', the primary [[vector]] in the northeastern U.S.) has a two-year life cycle, first progressing from larva to nymph, and then from nymph to adult. The [[tick]] feeds only once at each stage. In the fall, large acorn forests attract deer as well as mice, chipmunks and other small [[Rodent|rodents]] infected with ''[[B. burgdorferi]]''. During the following spring, the [[Tick|ticks]] lay their eggs. The [[rodent]] population then "booms." [[Tick]] eggs hatch into larvae, which feed on the [[Rodent|rodents]]; thus the larvae acquire [[infection]] from the [[Rodent|rodents]]. (Note: At this stage, it is proposed that tick infestation may be controlled using acaricides ([[miticide]]).
 
Adult [[ticks]] may also transmit disease to humans. After feeding, female adult [[Tick|ticks]] lay their eggs on the ground, and the cycle is complete. On the west coast, [[Lyme disease]] is spread by the western black-legged tick (''[[Ixodes pacificus]]''), which has a different life cycle.
 
The risk of acquiring [[Lyme disease]] does not depend on the existence of a local deer population, as is commonly assumed. New research suggests that eliminating deer from smaller areas (less than 2.5 hectares or 6.2 acres) may in fact lead to an increase in [[tick]] density and the rise of "[[tick-borne disease]] hotspots".<ref name="Perkins">{{cite journal |author=Perkins SE, Cattadori IM, Tagliapietra V, Rizzoli AP, Hudson PJ |title=Localized deer absence leads to tick amplification |journal=Ecology |volume=87 |issue=8 |pages=1981-6 |year=2006 |pmid=16937637 }}</ref>
 
==Differentiating B. burgdorferi from B. mayonii==


<gallery>
The following table demonstrates key clinical and epidemiological features  that distinguish ''B. burgdorferi'' from ''B. mayonii'':<ref name="PrittMead2016">{{cite journal|last1=Pritt|first1=Bobbi S|last2=Mead|first2=Paul S|last3=Johnson|first3=Diep K Hoang|last4=Neitzel|first4=David F|last5=Respicio-Kingry|first5=Laurel B|last6=Davis|first6=Jeffrey P|last7=Schiffman|first7=Elizabeth|last8=Sloan|first8=Lynne M|last9=Schriefer|first9=Martin E|last10=Replogle|first10=Adam J|last11=Paskewitz|first11=Susan M|last12=Ray|first12=Julie A|last13=Bjork|first13=Jenna|last14=Steward|first14=Christopher R|last15=Deedon|first15=Alecia|last16=Lee|first16=Xia|last17=Kingry|first17=Luke C|last18=Miller|first18=Tracy K|last19=Feist|first19=Michelle A|last20=Theel|first20=Elitza S|last21=Patel|first21=Robin|last22=Irish|first22=Cole L|last23=Petersen|first23=Jeannine M|title=Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study|journal=The Lancet Infectious Diseases|volume=16|issue=5|year=2016|pages=556–564|issn=14733099|doi=10.1016/S1473-3099(15)00464-8}}</ref><ref name="urlNew Lyme-disease-causing bacteria species discovered| CDC Online Newsroom | CDC">{{cite web |url=https://www.cdc.gov/media/releases/2016/p0208-lyme-disease.html |title=New Lyme-disease-causing bacteria species discovered&#124; CDC Online Newsroom &#124; CDC |format= |work= |accessdate=}}</ref>


Image: Borrelia44.jpeg| Histopathology showing Borrelia burgdorferi spirochetes in Lyme disease. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
{| style="font-size: 85%;"
! style="width: 80px; background: #4479BA; text-align: center;" |{{fontcolor|#FFF| General information}}
! style="width: 300px; background: #4479BA; text-align: center;" | {{fontcolor|#FFF|'''''B. burgdorferi'''''}}
! style="width: 300px; background: #4479BA; text-align: center;" | {{fontcolor|#FFF|'''''B. mayonii'''''
}}
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;" | '''Transmission'''
| style="background: #DCDCDC; padding: 5px;" |[[Tick]] bite
| style="background: #DCDCDC; padding: 5px;" |[[Tick]] bite
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;" | '''Distribution in the USA'''
| style="background: #DCDCDC; padding: 5px;" |Northeast, Mid-Atlantic, and Midwest regions
| style="background: #DCDCDC; padding: 5px;" |Midwest region
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;" | '''Bacteria Concentration in Blood (Spirochetemia)'''
| style="background: #DCDCDC; padding: 5px;" |Lower
| style="background: #DCDCDC; padding: 5px;" |Higher
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;" | '''Early Symptoms'''
| style="background: #DCDCDC; padding: 5px;" |[[Fever]], [[headache]], [[rash]], [[neck pain]]
| style="background: #DCDCDC; padding: 5px;" |[[Fever]], [[headache]], [[rash]], [[neck pain]]
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;" | '''Late Symptoms and Complications'''
| style="background: #DCDCDC; padding: 5px;" |[[Joint pain]] and [[Arthritis]]
| style="background: #DCDCDC; padding: 5px;" |[[Joint pain]] and [[Arthritis]]
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;" | '''Nausea / Vomiting?'''
| style="background: #DCDCDC; padding: 5px;" |No
| style="background: #DCDCDC; padding: 5px;" |Yes
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;" | '''Rash Characteristics'''
| style="background: #DCDCDC; padding: 5px;" |Bull's-eye target lesion
| style="background: #DCDCDC; padding: 5px;" |Diffuse rash
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;" |'''Diagnosis'''
| style="background: #DCDCDC; padding: 5px;" |[[Serology]] or [[PCR]]
| style="background: #DCDCDC; padding: 5px;" |[[Serology]] or [[PCR]]
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;" | '''Treatment'''
| style="background: #DCDCDC; padding: 5px;" |[[Doxycycline]]
| style="background: #DCDCDC; padding: 5px;" |[[Doxycycline]]
|}


Image: Borrelia38.jpeg| White-footed mouse, Peromyscus leucopus, which is a host of ticks thatare known to carry the bacteria, Borrelia burgdorferi, responsible for Lyme disease. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


Image: Borrelia37.jpeg| “Corkscrew-shaped” bacteria known as Borrelia burgdorferi, which is the pathogen responsible for causing Lyme disease (400x mag). <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
==Gallery==


Image: Borrelia36.png| Facial palsy caused by an infection by the bacterial spirochete Borrelia burgdorferi, and was subsequently diagnosed with Lyme disease. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
<gallery>


Image: Borrelia25.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Borrelia44.jpeg| Histopathology showing Borrelia burgdorferi spirochetes in Lyme disease. -  <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


Image: Borrelia38.jpeg| White-footed mouse, Peromyscus leucopus, which is a host of ticks thatare known to carry the bacteria, Borrelia burgdorferi, responsible for Lyme disease. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


Image: Borrelia26.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Borrelia37.jpeg| “Corkscrew-shaped” bacteria known as Borrelia burgdorferi, which is the pathogen responsible for causing Lyme disease (400x mag). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>




Image: Borrelia25.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


Image: Borrelia20.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


Image: Borrelia26.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


Image: Borrelia21.jpeg| Borrelia burgdorferi bacteria derived from a pure culture.  <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>




Image: Borrelia22.jpeg|Borrelia burgdorferi bacteria derived from a pure culture.<SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Borrelia20.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>




Image: Borrelia23.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Borrelia21.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. -  <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>




Image: Borrelia24.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
Image: Borrelia22.jpeg|Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>




</gallery>
Image: Borrelia23.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


==Treatment==
===Antimicrobial regimen===
* Lyme disease <ref>{{cite journal |vauthors=Wormser GP, 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 |title=The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America |journal=Clin. Infect. Dis. |volume=43 |issue=9 |pages=1089–134 |year=2006 |pmid=17029130 |doi=10.1086/508667 |url=}}</ref>
:*1. '''Early Lyme Disease'''
::*1.1 '''Erythema migrans'''
:::*1.1.1 '''Adult'''
::::* Preferred regimen (1): [[Doxycycline]] 100 mg PO bid for 10-21 days 
::::* Preferred regimen (2): [[Amoxicillin]] 500 mg PO tid for 14-21 days
::::* Preferred regimen (3): [[Cefuroxime axetil]] 500 mg bid for 14-21 days
::::* Alternatie regimen (1): [[Azithromycin]] 500 mg PO qd for 7–10 days 
::::* Alternatie regimen (2): [[Clarithromycin]] 500 mg PO bid for 14–21 days (if the patient is not pregnant)


::::* Alternatie regimen (3): [[Erythromycin]] 500 mg PO qid for 14–21 days
Image: Borrelia24.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


:::*1.1.2 '''Pediatric'''
<gallery>


::::*1.1.2.1 '''children <8 years of age'''
Image: Anaplasma phagocytophilum05.jpeg| Dorsal view of an adult female western blacklegged tick, whichs transmit Borrelia burgdorferi (agent of Lyme disease). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>  
:::::* Preferred regimen (1): [[Amoxicillin]] 50 mg/kg PO per day in 3 divided doses (maximum of 500 mg per dose)   


:::::* Preferred regimen (2): [[Cefuroxime axetil]] 30 mg/kg PO per day in 2 divided doses（maximum, 500 mg per dose)
Image: Anaplasma phagocytophilum04.jpeg| Dorsal view of an adult female western blacklegged tick, whichs transmit Borrelia burgdorferi (agent of Lyme disease). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL> 
:::*1.1.2.2 '''children ≥8 years of age'''


:::::* Preferred regimen (1): [[Doxycycline]] 4 mg/kg PO per day in 2 divided doses（maximum, 100 mg per dose）
Image: Anaplasma phagocytophilum03.jpeg| Dorsal view of engorged female tick, extracted from the skin of a pet cat (26X mag). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL> 
:::::* Preferred regimen (2): [[Azithromycin]] 10 mg/kg PO qd (maximum, 500 mg qd)


:::::* Preferred regimen (3): [[Clarithromycin]] 7.5 mg/kg PO bid (maximum, 500 mg per dose)  
Image: Anaplasma phagocytophilum02.jpeg| Dorsal view of engorged female tick in the process of obtaining its blood meal (207X magnification). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>  


:::::* Preferred regimen (4): [[Erythromycin]] 12.5 mg/kg PO qid (maximum, 500 mg per dose)
Image: Anaplasma phagocytophilum01.jpeg| Scanning electron micrographic (SEM) image depicts dorsal view of engorged female tick (201X magnification). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL> 


::*1.2 '''When erythema migrans cannot be reliably distinguished from community-acquired bacterial cellulitis'''
<SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
:::* Preferred regimen: [[Amoxicillin-Clavulanate]] 500 mg PO tid
:::* Pediatric regimen: [[Amoxicillin-Clavulanate]] 50 mg/kg per day in 3 divided doses (maximum, 500 mg per dose)


::*1.3 '''Lyme carditis'''
Image: Borrelia02.jpeg| Photomicrographic montage using the immunofluorescent antibody technique (IFA) used to produce this B. burgdorferi multicolored image. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
:::* Preferred regimen: [[Ceftriaxone]] 2 g IV q24h for 10–28 days
:::* Note: patients with advanced heart block, a temporary pacemaker may be required; expert consultation with a cardiologist is recommended; Use of the pacemaker may be discontinued when the advanced heart block has resolved; An oral antibiotic treatment regimen should be used for completion of therapy and for outpatients, as is used for patients with erythema migrans without carditis (see above)


::*1.4 '''Borrelial lymphocytoma'''
Image: Borrelia04.jpeg| Lateral view of female deer tick, Ixodes scapularis, with its abdomen engorged with a host blood meal. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
:::* Preferred regimen: The same regimens used to treat patients with erythema migrans (see above)  


:*2. '''Late Lyme Disease'''
Image: Borrelia05.jpeg| Peripheral blood from a newborn child indicates the presence of numerous Borrelia hermsii spirochetes (arrows), consistent with a tickborne relapsing fever (TBRF) infection. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
::*2.1 '''Lyme arthritis'''
:::* Preferred regimen (1): [[Doxycycline]] 100 mg PO bid


:::* Preferred regimen (2): [[Amoxicillin]] 500 mg PO tid
:::* Alternative regimen: [[Cefuroxime axetil]] 500 mg PO bid for 28 days
:::* Pediatric regimen: [[Amoxicillin]] 50 mg/kg per day in 3 divided doses (maximum, 500 mg per dose); [[Cefuroxime axetil]] 30 mg/kg per day in 2 divided doses (maximum,500 mg per dose); (≥8 years of age) [[Doxycycline]] 4 mg/ kg per day in 2 divided doses (maximum, 100 mg per dose)
:::* Note: For patients who have persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy, we recommend re-treatment with another 4-week course of oral antibiotics or with a 2–4 weeks course of [[Ceftriaxone]] IV


::*2.2 '''patients with arthritis and objective evidence of neurologic disease'''
Image: Borrelia12.jpeg| Dorsal view of a soft tick, Ornithodoros hermsi, which is a known vector for the disease tick-borne relapsing fever (TBRF) (6.5x mag). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
:::* Preferred regimen: [[Ceftriaxone]] IV for 2–4 weeks
:::* Alternative regimen (1): [[Cefotaxime]] IV


:::* Alternative regimen (1): [[Penicillin G]] IV
Image: Borrelia16.jpeg| Deer tick, Ixodes scapularis. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
:::* Pediatric regime: [[Ceftriaxone]]; [[Cefotaxime]]; [[Penicillin G]] IV


::*2.3 '''Acrodermatitis chronica atrophicans'''
:::* Preferred regimen (1): [[Doxycycline]] 100 mg PO bid for 21 days
:::* Preferred regimen (2): [[Amoxicillin]] 500 mg PO tid for 21 days
:::* Preferred regimen (3): [[Cefuroxime axetil]] 500 mg PO bid for 21 days


:*3. '''Post–Lyme Disease Syndromes'''
Image: Borrelia20.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
:::* Preferred regimen: Further antibiotic therapy for Lyme disease should not be given unless there are objective findings of active disease (including physical findings, abnormalities on cerebrospinal or synovial fluid analysis, or changes on formal neuropsychologic testing)


====Lyme neuroborreliosis====


*1. '''Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines'''<ref>{{Cite journal| doi = 10.1086/508667| issn = 1537-6591| volume = 43| issue = 9| pages = 1089–1134| last1 = Wormser| first1 = Gary P.| last2 = Dattwyler| first2 = Raymond J.| last3 = Shapiro| first3 = Eugene D.| last4 = Halperin| first4 = John J.| last5 = Steere| first5 = Allen C.| last6 = Klempner| first6 = Mark S.| last7 = Krause| first7 = Peter J.| last8 = Bakken| first8 = Johan S.| last9 = Strle| first9 = Franc| last10 = Stanek| first10 = Gerold| last11 = Bockenstedt| first11 = Linda| last12 = Fish| first12 = Durland| last13 = Dumler| first13 = J. Stephen| last14 = Nadelman| first14 = Robert B.| title = The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America| journal = Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America| date = 2006-11-01| pmid = 17029130}}</ref>
Image: Borrelia21.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
:*1.1 '''Early neurologic disease'''
::*1.1.1 '''Cranial nerve palsy (adult)'''
:::* Preferred regimen (1): [[Amoxicillin]] 500 mg PO tid for 14 (14–21) days 


:::* Preferred regimen (2): [[Doxycycline]] 100 mg PO bid for 14 (14–21) days 


:::* Preferred regimen (3): [[Cefuroxime]] 500 mg PO bid for 14 (14–21) days
Image: Borrelia22.jpeg|Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
:::* Alternative regimen (1): [[Azithromycin]] 500 mg PO qd for 7–10 days


:::* Alternative regimen (2): [[Clarithromycin]] 500 mg PO bid for 14–21 days (not for pregnant)


:::* Alternative regimen (3): [[Erythromycin]] 500 mg PO qid for 14–21 days
Image: Borrelia23.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


::*1.1.2 '''Cranial nerve palsy (pediatric)'''
:::* Preferred regimen (1): [[Amoxicillin]] 50 mg/kg/day PO tid (Maxmum, 500 mg/dose) for 14 (14–21) days


:::* Preferred regimen (2): [[Doxycycline]] (for children aged ≥ 8 years) 4 mg/kg/day PO q12h (Maxmum, 100 mg/dose) for 14 (14–21) days 
Image: Borrelia24.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


:::* Preferred regimen (3): [[Cefuroxime]] 30 mg/kg/day PO q12h (Maxmum, 500 mg/dose) for 14 (14–21) days
:::* Alternative regimen (1): [[Azithromycin]] 10 mg/kg/day PO (Maxmum, 500 mg/dose) for 7–10 days


:::* Alternative regimen (2): [[Clarithromycin]] 7.5 mg/kg PO bid (Maxmum, 500 mg/dose) for 14–21 days
Image: Borrelia25.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


:::* Alternative regimen (3): [[Erythromycin]] 12.5 mg/kg PO bid (Maxmum, 500 mg/dose) for 14–21 days


::*1.1.3 '''Meningitis or radiculopathy (adult)'''
Image: Borrelia26.jpeg| Borrelia burgdorferi bacteria derived from a pure culture. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
:::* Preferred regimen: [[Ceftriaxone]] 2 g IV q24h for 14 (10–28) days
:::* Alternative regimen (1): [[Cefotaxime]] 2 g IV q8h for 14 (10–28) days 


:::* Alternative regimen (2): [[Penicillin G]] 18–24 MU/day IV q4h for 14 (10–28) days
:::* Note: for nonpregnant adult patients intolerant of β-lactam agents, [[Doxycycline]] 200–400 mg/day PO/IV q12h may be considered.


::*1.1.4 '''Meningitis or radiculopathy (pediatric)'''
Image: Borrelia27.jpeg|Dorsal view of engorged female tick in the process of obtaining its blood meal (201x mag). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
:::* Preferred regimen: [[Ceftriaxone]] 50–75 mg/kg IV q24h (Maxmum, 2 g/day) for 14 (10–28) days
:::* Alternative regimen (1): [[Cefotaxime]] 150–200 mg/kg/day IV q6-8h (Maxmum, 6 g/day) for 14 (10–28) days 


:::* Alternative regimen (2): [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h (Maxmum, 18–24 MU/day) for 14 (10–28) days
:::* Note: for children ≥ 8 years of age intolerant of β-lactam agents, [[Doxycycline]] 4–8 mg/kg/day PO/IV q12h, max 200–400 mg/day may be considered


:*1.2 '''Late neurologic disease'''
Image: Borrelia28.jpeg| Dorsal view of engorged female tick, extracted from the skin of a pet cat (26x mag). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
::*1.2.1 '''Central or peripheral nervous system disease (adult)'''
:::* Preferred regimen: [[Ceftriaxone]] 2 g IV q24h for 14 (10–28) days
:::* Alternative regimen (1): [[Cefotaxime]] 2 g IV q8h for 14 (10–28) days 


:::* Alternative regimen (2): [[Penicillin G]] 18–24 MU/day IV q4h for 14 (10–28) days


::*1.2.2 '''Central or peripheral nervous system disease (pediatric)'''
Image: Borrelia29.jpeg| Male Dermacentor sp. tick found upon a cat (95x mag). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
:::* Preferred regimen: [[Ceftriaxone]] 50–75 mg/kg IV q24h (Maxmum, 2 g/day) for 14 (10–28) days.
:::* Alternative regimen (1): [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h (Maxmum, 6 g/day) for 14 (10–28) days


:::* Alternative regimen (2): [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h (Maxmum, 18–24 MU/day) for 14 (10–28) days
Image: Borrelia30.jpeg| Dorsal view of male Dermacentor sp. tick found on a cat (3043x mag). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


*2. '''American Academy of Neurology (AAN) Practice Parameter'''<ref>{{Cite journal| doi = 10.1212/01.wnl.0000265517.66976.28| issn = 1526-632X| volume = 69| issue = 1| pages = 91–102| last1 = Halperin| first1 = J. J.| last2 = Shapiro| first2 = E. D.| last3 = Logigian| first3 = E.| last4 = Belman| first4 = A. L.| last5 = Dotevall| first5 = L.| last6 = Wormser| first6 = G. P.| last7 = Krupp| first7 = L.| last8 = Gronseth| first8 = G.| last9 = Bever| first9 = C. T.| last10 = Quality Standards Subcommittee of the American Academy of Neurology| title = Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology| journal = Neurology| date = 2007-07-03| pmid = 17522387}}</ref>
Image: Borrelia33.jpeg| Dorsal view of a female "lone star tick", Amblyomma americanum. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
:*2.1 '''Meningitis'''
::* Preferred regimen (1): [[Ceftriaxone]] 2 g IV q24h for 14 days


::* Preferred regimen (2):[[Cefotaxime]] 2 g IV q8h for 14 days 
Image: Borrelia34.jpeg| Anterior view of engorged female "lone star tick", Amblyomma americanum. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


::* Preferred regimen (3):[[Penicillin G]] 18–24 MU/day q4h for 14 days
Image: Borrelia35.jpeg| Ventral view of engorged female "lone star tick" Amblyomma americanum. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
::* Alternative regimen: [[Doxycycline]] 100–200 mg BID for 14 days
::* Pediatric regimen: [[Ceftriaxone]] 50–75 mg/kg/day IV q24h, max 2 g/day; [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h, max 6 g/day; [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h, max 18–24 MU/day; [[Doxycycline]] (≥ 8 y/o) 4–8 mg/kg/day q12h, max 200 mg/day


:*2.2 '''Any neurologic syndrome with CSF pleocytosis'''
Image: Borrelia37.jpeg| “Corkscrew-shaped” bacteria known as Borrelia burgdorferi, the pathogen responsible for causing Lyme disease (400x mag). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
::* Preferred regimen (1): [[Ceftriaxone]] 2 g IV q24h for 14 days


::* Preferred regimen (2): [[Cefotaxime]] 2 g IV q8h for 14 days 


::* Preferred regimen (3): [[Penicillin G]] 18–24 MU/day IV q4h for 14 days
Image: Borrelia38.jpeg| White-footed mouse, Peromyscus leucopus, which is a wild rodent reservoir host of ticks, which are known to carry the bacteria, Borrelia burgdorferi, responsible for Lyme disease. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
::* Alternative regimen: [[Doxycycline]] 100–200 mg BID for 14 days
::* Pediatric regimen: [[Ceftriaxone]] 50–75 mg/kg/day IV q24h, max 2 g; [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h, max 6 g/day; [[Penicillin G]] 200,000–400,000 U/kg/day q4h, max 18–24 MU/day; [[Doxycycline]] (≥ 8 y/o) 4–8 mg/kg/day q12h, max 200 mg/day


:*2.3 '''Peripheral nervous system disease (radiculopathy, diffuse neuropathy, mononeuropathy multiplex, cranial neuropathy; normal CSF)'''
Image: Borrelia39.jpeg| This photograph of a whitetail deer, Odocoileus virginianus, was taken during a Lyme disease field investigation in 1993. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
::* Preferred regimen: [[Doxycycline]] 100–200 mg BID for 14 days
::* Alternative regimen (1): [[Ceftriaxone]] 2 g IV q24h for 14 days 


::* Alternative regimen (2): [[Cefotaxime]] 2 g IV q8h for 14 days 


::* Alternative regimen (3): [[Penicillin G]] 18–24 MU/day IV q4h for 14 days
Image: Borrelia40.jpeg| This is a dorsal view of the “soft tick” Carios kelleyi, formerly Ornithodoros kelleyi, or the “Bat Tick”. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
::* Pediatric regimen: [[Doxycycline]] (≥ 8 y/o) 4–8 mg/kg/day q12h, max 200 mg/day; [[Ceftriaxone]] 50–75 mg/kg/day IV q24h, max 2 g/day; [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h, max 6 g/day; [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h, max 18–24 MU/day; [[Doxycycline]] (≥ 8 y/o) 4–8 mg/kg/day q12h, max 200 mg/day


:*2.4 '''Encephalomyelitis'''
::* Preferred regimen (1): [[Ceftriaxone]] 2 g IV q24h for 14 days


::* Preferred regimen (2): [[Cefotaxime]] 2 g IV q8h for 14 days 
Image: Borrelia41.jpeg| This is a dorsal view of the “soft tick” Carios kelleyi, formerly Ornithodoros kelleyi, or the “Bat Tick”. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


::* Preferred regimen (3): [[Penicillin G]] 18–24 MU/day q4h for 14 days
Image: Borrelia42.jpeg| This is a female “Lone star tick”, Amblyomma americanum, and is found in the southeastern and midatlantic United States. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
::* Pediatric regimen: [[Ceftriaxone]] 50–75 mg/kg/day IV q24h, max 2 g/day; [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h, max 6 g/day; [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h, max 18–24 MU/day


:*2.5 '''Encephalopathy'''
Image: Borrelia43.jpeg| These "black-legged ticks", Ixodes scapularis, also referred to as I. dammini, are found on a wide rage of hosts including mammals, birds and reptiles. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
::* Preferred regimen (1): [[Ceftriaxone]] 2 g IV q24h for 14 days


::* Preferred regimen (2): [[Cefotaxime]] 2 g IV q8h for 14 days 
Image: Borrelia44.jpeg| Histopathology showing Borrelia burgdorferi spirochetes in Lyme disease. Dieterle silver stain. - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>


::* Preferred regimen (3): [[Penicillin G]] 18–24 MU/day q4h for 14 days
Image: Borrelia37.jpeg| “Corkscrew-shaped” bacteria known as Borrelia burgdorferi, which is the pathogen responsible for causing Lyme disease (400x mag). - <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp Source: Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
::* Pediatric regimen: [[Ceftriaxone]] 50–75 mg/kg/day IV q24h, max 2 g/day; [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h, max 6 g/day; [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h, max 18–24 MU/day


:*2.6 '''Post-treatment Lyme syndrome'''
</gallery>
::* Preferred regimen: symptomatic management
::* Note: Antibiotic therapy is not indicated.


==References==
==References==
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discussion of different citation methods and how to generate
footnotes using the <ref> & </ref> tags and the {{Reflist}} template
-------------------------------------------------------------------- -->
{{Reflist|2}}
{{Reflist|2}}


==See Also==
==See Also==
*[[Allen Steere]]
*Allen Steere
*[[Jorge benach|Jorge Benach]]
*Jorge Benach


==External Links==
==External Links==
*[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=138 NCBI Borrelia Taxonomy Browser]
*[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=138 NCBI Borrelia Taxonomy Browser]
*[http://microbewiki.kenyon.edu/index.php/Borrelia Borrelia Microbe Wiki Page]
*[http://microbewiki.kenyon.edu/index.php/Borrelia Borrelia Microbe Wiki Page]
*[http://cmr.tigr.org/tigr-scripts/CMR/GenomePage.cgi?database=gbb Borrelia burgdoferi B31 Genome Page]==External links==
*[http://www.molecularalzheimer.org/Atlasof_borrelia.html Atlas of Borrelia (images of spirochetal, spheroplast and granular forms)]
*[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=138 NCBI Taxonomy Browser - Borrelia]
*[http://cmr.tigr.org/tigr-scripts/CMR/GenomePage.cgi?database=gbb Borrelia burgdoferi B31 Genome Page]
*[http://cmr.tigr.org/tigr-scripts/CMR/GenomePage.cgi?database=gbb Borrelia burgdoferi B31 Genome Page]
*[http://cmr.tigr.org/tigr-scripts/CMR/GenomePage.cgi?org=ntbg01 Borrelia Garinii PBi Genome Page]
*[http://cmr.tigr.org/tigr-scripts/CMR/GenomePage.cgi?org=ntba07 Borrelia Afzelli PKo Gemonme Page]
*[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]






[[de:Wanderröte]]
[[de:Wanderröte]]


[[Category:Insect-borne diseases]]
[[Category:Insect-borne diseases]]

Latest revision as of 19:38, 18 August 2017

Borrelia burgdorferi
Scientific classification
Kingdom: Bacteria
Phylum: Spirochaetes
Class: Spirochaetes
Order: Spirochaetales
Genus: Borrelia
Species: B. burgdorferi
Binomial name
Borrelia burgdorferi

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This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Lyme disease.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Raviteja Guddeti, M.B.B.S. [2], Ilan Dock, B.S. Template:Seealso Template:Seealso (a newly discovered Borrelia species that has been associated with Lyme disease)

Main article: Lyme disease microbiology

Overview

Borrelia burgdorferi is species of bacteria of the spirochete class of the genus Borrelia. B. burgdorferi is predominant in North America, but also exists in Europe, and is the causative agent of Lyme disease. It is a zoonotic, vector-borne disease transmitted by ticks and is named after the researcher Willy Burgdorfer who first isolated the bacterium in 1982. B. burgdorferi is one of the few pathogenic bacteria that can survive without iron, having replaced all of its iron-sulphur cluster enzymes with enzymes that use manganese, thus avoiding the problem many pathogenic bacteria face in acquiring iron. B. burgdorferi infections have been linked to non-Hodgkin lymphomas.[1]

Organism

Borrelia burgdorferi the causative agent of Lyme disease (borreliosis). Magnified 400 times. - Source: Public Health Image Library
  • Borrelia are microaerophillic and slow-growing—the primary reason for the long delays when diagnosing Lyme disease—and have been found to have greater strain diversity than previously estimated.[2] The strains differ in clinical symptoms and/or presentation as well as geographic distribution.[3]


Structure and growth

B. burgdorferi is a highly specialized, motile, two-membrane, spiral-shaped spirochete ranging from about 9 to 32 micrometers in length. It is often described as gram-negative and has an outer membrane with lipopolysaccharide (LPS), though it stains only weakly in the Gram stain. B. burgdorferi is a microaerophilic organism, requiring little oxygen to survive. It lives primarily as an extracellular pathogen, although it can also hide intracellularly (see Mechanisms of persistence section).

Like other spirochetes such as T. pallidum (the agent of syphilis), B. burgdorferi has an axial filament composed of flagella which run lengthways between its cell wall and outer membrane. This structure allows the spirochete to move efficiently in corkscrew fashion through viscous media, such as connective tissue. As a result, B. burgdorferi can disseminate throughout the body within days to weeks of infection, penetrating deeply into tissue where the immune system and antibiotics may not be able to eradicate the infection.

B. burgdorferi is very slow growing, with a doubling time of 12-18 hours[6] (in contrast to pathogens such as Streptococcus and Staphylococcus, which have a doubling time of 20-30 minutes). Since most antibiotics kill bacteria only when they are dividing, this longer doubling time necessitates the use of relatively longer treatment courses for Lyme disease. Antibiotics are most effective during the growth phase, which for B. burgdorferi occurs in four-week cycles.

Outer surface proteins

The outer membrane of Borrelia burgdorferi is composed of various unique outer surface proteins (Osp) that have been characterized (OspA through OspF). They are presumed to play a role in virulence.

OspA and OspB are by far the most abundant outer surface proteins.

The OspA and OspB genes encode the major outer membrane proteins of the B. burgdorferi. The two Osp proteins show a high degree of sequence similarity, indicating a recent evolutionary event. Molecular analysis and sequence comparison of OspA and OspB with other proteins has revealed similarity to the signal peptides of prokaryotic lipoproteins.[7]Virtually all spirochetes in the midgut of an unfed nymph tick express OspA.

OspC is an antigen-detection of its presence by the host organism and can stimulate an immune response. While each individual bacterial cell contains just one copy of the gene encoding OspC, populations of B. burgdorferi have shown high levels of variation among individuals in the gene sequence for OspC.[8] OspC is likely to play a role in transmission from vector to host, since it has been observed that the protein is only expressed in the presence of mammalian blood or tissue.[9]

The functions of OspD are unknown.

OspE and OspF are structurally arranged in tandem as one transcriptional unit under the control of a common promoter.[10]

In transmission to the mammalian host, when the nymphal tick begins to feed, and the spirochetes in the midgut begin to multiply rapidly, most spirochetes cease expressing OspA on their surface. Simultaneous with the disappearance of OspA, the spirochete population in the midgut begins to express a OspC. Upregulation of OspC begins during the first day of feeding and peaks 48 hours after attachment.[11]

General Tick Life Cycle

This image displays an example of the tick lifecycle, based on stages and the months that they are most likely to occur during. - Source: https://www.nih.gov

A tick's life cycle is composed of four stages: hatching (egg), nymph (six legged), nymph (eight legged), and an adult.

Ticks require blood meal to survive through their life cycle.

Hosts for tick blood meals include mammals, birds, reptiles, and amphibians. Ticks will most likely transfer between different hosts during the different stages of their life cycle.

Humans are most often targeted during the nymph and adult stages of the life cycle.

Life cycle is also dependent on seasonal variation.

Ticks will go from eggs to larva during the summer months, infecting bird or rodent host during the larval stage.

Larva will infect the host from the summer until the following spring, at which point they will progress into the nymph stage.

During the nymph stage, a tick will most likely seek a mammal host (including humans).

A nymph will remain with the selected host until the following fall at which point it will progress into an adult.

As an adult, a tick will feed on a mammalian host. However unlike previous stages, ticks will prefer larger mammals over rodents.

The average tick life cycle requires three years for completion.

Different species will undergo certain variations within their individual life cycles. [12]

Borrelia burgdoferi lifecycle

The life-cycle concept encompassing reservoirs and infections in multiple hosts has recently been expanded to encompass forms of the spirochete which differ from the motile corkscrew form, and these include cystic forms spheroplast-like, straighted non-coiled bacillary forms which are immotile due to flagellin mutations and granular forms coccoid in profile. The model of Plasmodium species Malaria with multiple parasitic profiles demonstrable in various host insects and mammals is a hypothesized model for a similarly complex proposed Borrelia spirochete life cycle. [13] [14]

Whereas B. burgdorferi is most associated with deer tick and the white footed mouse,[15] B. afzelii is most frequently detected in rodent-feeding vector ticks, B. garinii and B. valaisiana appear to be associated with birds. Both rodents and birds are competent reservoir hosts for Borrelia burgdorferi sensu stricto. The resistance of a genospecies of Lyme disease spirochetes to the bacteriolytic activities of the alternative immune complement pathway of various host species may determine its reservoir host association.

Ecology

Urbanization and other anthropogenic factors can be implicated in the spread of the Lyme disease into the human population. In many areas, expansion of suburban neighborhoods has led to the gradual deforestation of surrounding wooded areas and increasing "border" contact between humans and tick-dense areas. Human expansion has also resulted in a gradual reduction of the predators that normally hunt deer as well as mice, chipmunks and other small rodents -- the primary reservoirs for Lyme disease. As a consequence of increased human contact with host and vector, the likelihood of transmission of Lyme to residents of endemic area has greatly increased.[16][17] Researchers are also investigating possible links between global warming and the spread of vector-borne diseases including Lyme disease.[18]

The deer tick (Ixodes scapularis, the primary vector in the northeastern U.S.) has a two-year life cycle, first progressing from larva to nymph, and then from nymph to adult. The tick feeds only once at each stage. In the fall, large acorn forests attract deer as well as mice, chipmunks and other small rodents infected with B. burgdorferi. During the following spring, the ticks lay their eggs. The rodent population then "booms." Tick eggs hatch into larvae, which feed on the rodents; thus the larvae acquire infection from the rodents. (Note: At this stage, it is proposed that tick infestation may be controlled using acaricides (miticide).

Adult ticks may also transmit disease to humans. After feeding, female adult ticks lay their eggs on the ground, and the cycle is complete. On the west coast, Lyme disease is spread by the western black-legged tick (Ixodes pacificus), which has a different life cycle.

The risk of acquiring Lyme disease does not depend on the existence of a local deer population, as is commonly assumed. New research suggests that eliminating deer from smaller areas (less than 2.5 hectares or 6.2 acres) may in fact lead to an increase in tick density and the rise of "tick-borne disease hotspots".[19]

Differentiating B. burgdorferi from B. mayonii

The following table demonstrates key clinical and epidemiological features that distinguish B. burgdorferi from B. mayonii:[20][21]

General information B. burgdorferi B. mayonii

Transmission Tick bite Tick bite
Distribution in the USA Northeast, Mid-Atlantic, and Midwest regions Midwest region
Bacteria Concentration in Blood (Spirochetemia) Lower Higher
Early Symptoms Fever, headache, rash, neck pain Fever, headache, rash, neck pain
Late Symptoms and Complications Joint pain and Arthritis Joint pain and Arthritis
Nausea / Vomiting? No Yes
Rash Characteristics Bull's-eye target lesion Diffuse rash
Diagnosis Serology or PCR Serology or PCR
Treatment Doxycycline Doxycycline


Gallery

References

  1. ↑ Guidoboni M, Ferreri AJ, Ponzoni M, Doglioni C, Dolcetti R (2006). "Infectious agents in mucosa-associated lymphoid tissue-type lymphomas: pathogenic role and therapeutic perspectives". Clinical lymphoma & myeloma. 6 (4): 289–300. PMID 16507206.
  2. ↑ Bunikis J, Garpmo U, Tsao J, Berglund J, Fish D, Barbour AG (2004). "Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe" (PDF). Microbiology. 150 (Pt 6): 1741–55. PMID 15184561.
  3. ↑ Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed. ed.). McGraw Hill. ISBN 0-8385-8529-9.
  4. ↑ Felsenfeld O (1971). Borrelia: Strains, Vectors, Human and Animal Borreliosis. St. Louis: Warren H. Green, Inc.
  5. ↑ CBS News Lyme Disease. http://www.cbsnews.com/news/lyme-disease-just-got-nastier/ Accessed February 9, 2016.
  6. ↑ Kelly, R. T. (1984). Genus IV. Borrelia Swellengrebel 1907, 582AL. In Bergey's Manual of Systematic Bacteriology, vol. 1, pp. 57–62. Edited by N. R. Krieg & J. G. Holt. Baltimore: Williams & Wilkins.
  7. ↑ Bergstrom S. , Bundoc V.G. , Barbour A.G. Molecular analysis of linear plasmid-encoded major surface proteins, OspA and OspB, of the Lyme disease spirochaete Borrelia burgdorferi. Mol. Microbiol. 3 479-486 1989
  8. ↑ Girschick, J. and Singh, S.E. Molecular survival strategies of the lyme disease spirochete Borrelia burgdorferi. Sep, 2004. The Lancet Infectious Diseases: Volume 4, Issue 9, September 2004, Pages 575-583.
  9. ↑ Fikrig, E. and Pal, U. Adaptation of Borrelia burgdorferi in the vector and vertebrate host. Microbes and Infection Volume 5, Issue 7, June 2003, Pages 659-666. PMID 12787742
  10. ↑ Lam TT, Nguyen TP, Montgomery RR, Kantor FS, Fikrig E, Flavell RA. Outer surface proteins E and F of Borrelia burgdorferi, the agent of Lyme disease. Infect Immun. 1994 Jan;62(1):290-8.
  11. ↑ Schwan TG, Piesman J. Temporal changes in outer surface proteins A and C of the Lyme disease-associated spirochete, Borrelia burgdorferi, during the chain of infection in ticks and mice. J Clin Microbiol 2000;38:382-8.
  12. ↑ Life Cycle of Ticks that Bite Humans (2015). http://www.cdc.gov/ticks/life_cycle_and_hosts.html Accessed on December 30, 2015
  13. ↑ Macdonald AB. "A life cycle for Borrelia spirochetes?" Med Hypotheses. 2006;67(4):810-8. PMID 16716532
  14. ↑ Lymeinfo.net - LDAdverseConditions
  15. ↑ Wallis RC, Brown SE, Kloter KO, Main AJ Jr. Erythema chronicum migrans and lyme arthritis: field study of ticks. Am J Epidemiol. 1978 Oct;108(4):322-7.PMID 727201
  16. ↑ LoGiudice K, Ostfeld R, Schmidt K, Keesing F (2003). "The ecology of infectious disease: effects of host diversity and community composition on Lyme disease risk". Proc Natl Acad Sci U S A. 100 (2): 567–71. PMID 12525705.
  17. ↑ Patz J, Daszak P, Tabor G; et al. (2004). "Unhealthy landscapes: Policy recommendations on land use change and infectious disease emergence". Environ Health Perspect. 112 (10): 1092–8. PMID 15238283.
  18. ↑ Khasnis AA, Nettleman MD (2005). "Global warming and infectious disease". Arch. Med. Res. 36 (6): 689–96. doi:10.1016/j.arcmed.2005.03.041. PMID 16216650.
  19. ↑ Perkins SE, Cattadori IM, Tagliapietra V, Rizzoli AP, Hudson PJ (2006). "Localized deer absence leads to tick amplification". Ecology. 87 (8): 1981–6. PMID 16937637.
  20. ↑ Pritt, Bobbi S; Mead, Paul S; Johnson, Diep K Hoang; Neitzel, David F; Respicio-Kingry, Laurel B; Davis, Jeffrey P; Schiffman, Elizabeth; Sloan, Lynne M; Schriefer, Martin E; Replogle, Adam J; Paskewitz, Susan M; Ray, Julie A; Bjork, Jenna; Steward, Christopher R; Deedon, Alecia; Lee, Xia; Kingry, Luke C; Miller, Tracy K; Feist, Michelle A; Theel, Elitza S; Patel, Robin; Irish, Cole L; Petersen, Jeannine M (2016). "Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study". The Lancet Infectious Diseases. 16 (5): 556–564. doi:10.1016/S1473-3099(15)00464-8. ISSN 1473-3099.
  21. ↑ "New Lyme-disease-causing bacteria species discovered| CDC Online Newsroom | CDC".
  22. ↑ 22.00 22.01 22.02 22.03 22.04 22.05 22.06 22.07 22.08 22.09 22.10 22.11 22.12 22.13 22.14 22.15 22.16 22.17 22.18 22.19 22.20 22.21 22.22 22.23 22.24 22.25 22.26 22.27 22.28 22.29 22.30 22.31 22.32 22.33 22.34 22.35 22.36 22.37 22.38 22.39 22.40 22.41 22.42 "Public Health Image Library (PHIL)".

See Also

  • Allen Steere
  • Jorge Benach

External Links



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