Lyme disease - Wikipedia
文章推薦指數: 80 %
Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the Borrelia bacterium which is spread by ticks in the genus Ixodes. Lymedisease FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch InfectiousdiseasecausedbyBorreliabacteria,spreadbyticks Nottobeconfusedwithphytophotodermatitis,alsoknownas"limedisease". MedicalconditionLymediseaseOthernamesLymeborreliosisAnadultdeertick(mostcasesofLymearecausedbynymphalratherthanadultticks)SpecialtyInfectiousdiseaseSymptomsExpandingareaofrednessatthesiteofatickbite,fever,headache,tiredness[1]ComplicationsFacialnerveparalysis,arthritis,meningitis[1]UsualonsetAweekafterabite[1]CausesBorreliaspreadbyticks[2]DiagnosticmethodBasedonsymptoms,tickexposure,bloodtests[3]PreventionPreventionoftickbites(clothingthelimbs,DEET),doxycycline[2]MedicationDoxycycline,amoxicillin,ceftriaxone,cefuroxime[2]Frequency~476,000peryearinU.S.(2010-2018)[4][5] Lymedisease,alsoknownasLymeborreliosis,isavector-bornediseasecausedbytheBorreliabacteriumwhichisspreadbyticksinthegenusIxodes.[2][6][7]Themostcommonsignofinfectionisanexpandingredrash,knownaserythemamigrans,thatappearsatthesiteofthetickbiteaboutaweekafteritoccurred.[1]Therashistypicallyneitheritchynorpainful.[1]Approximately70–80%ofinfectedpeopledeveloparash.[1]Earlydiagnosiscanbedifficult.[8]Otherearlysymptomsmayincludefever,headache,andtiredness.[1]Ifuntreated,symptomsmayincludelossoftheabilitytomoveoneorbothsidesoftheface,jointpains,severeheadacheswithneckstiffness,orheartpalpitations,amongothers.[1]Monthstoyearslater,repeatedepisodesofjointpainandswellingmayoccur.[1]Occasionally,peopledevelopshootingpainsortinglingintheirarmsandlegs.[1]Despiteappropriatetreatment,about10to20%ofpeopledevelopjointpains,memoryproblems,andtirednessforatleastsixmonths.[1][9] LymediseaseistransmittedtohumansbythebitesofinfectedticksofthegenusIxodes.[10]IntheUnitedStates,ticksofconcernareusuallyoftheIxodesscapularistypeandmustbeattachedforatleast36hoursbeforethebacteriacanspread.[11][12]InEurope,Ixodesricinusticksmayspreadthebacteriamorequickly.[12][13]InNorthAmerica,thebacteriaBorreliaburgdorferi,B.bissettiae,andB.mayoniicauseLymedisease.[2][14][7]InEuropeandAsia,Borreliaafzelii,Borreliagarinii,B.spielmanii,and4otherspeciesalsocausethedisease.[2]Thediseasedoesnotappeartobetransmissiblebetweenpeople,byotheranimals,orthroughfood.[11]Diagnosisisbaseduponacombinationofsymptoms,historyoftickexposure,andpossiblytestingforspecificantibodiesintheblood.[3][15]Bloodtestsareoftennegativeintheearlystagesofthedisease.[2]Testingofindividualticksisnottypicallyuseful.[16] Preventionincludeseffortstopreventtickbitesbywearingclothingtocoverthearmsandlegs,andusingDEETorpicaridin-basedinsectrepellents.[2][6]Usingpesticidestoreduceticknumbersmayalsobeeffective.[2]Tickscanberemovedusingtweezers.[17]Iftheremovedtickwasfullofblood,asingledoseofdoxycyclinemaybeusedtopreventthedevelopmentofinfection,butisnotgenerallyrecommendedsincethedevelopmentofinfectionisrare.[2]Ifaninfectiondevelops,anumberofantibioticsareeffective,includingdoxycycline,amoxicillin,andcefuroxime.[2]Standardtreatmentusuallylastsfortwoorthreeweeks.[2]Somepeopledevelopafeverandmuscleandjointpainsfromtreatmentwhichmaylastforoneortwodays.[2]Inthosewhodeveloppersistentsymptoms,long-termantibiotictherapyhasnotbeenfoundtobeuseful.[2][18] LymediseaseisthemostcommondiseasespreadbyticksintheNorthernHemisphere.[19]Itisestimatedtoaffect300,000peopleayearintheUnitedStatesand65,000peopleayearinEurope.[2][20]Infectionsaremostcommoninthespringandearlysummer.[2]Lymediseasewasdiagnosedasaseparateconditionforthefirsttimein1975inLyme,Connecticut.[21]Itwasoriginallymistakenforjuvenilerheumatoidarthritis.[22]Thebacteriuminvolvedwasfirstdescribedin1981byWillyBurgdorfer.[23]Chronicsymptomsfollowingtreatmentarewelldescribedandareknownas"post-treatmentLymediseasesyndrome"(PTLDS).[18]PTLDSisdifferentfromchronicLymedisease,atermnolongersupportedbythescientificcommunityandusedindifferentwaysbydifferentgroups.[18][24]SomehealthcareprovidersclaimthatPTLDSiscausedbypersistentinfection,butthisisnotbelievedtobetruebecausenoevidenceofpersistentinfectioncanbefoundafterstandardtreatment.[25]AvaccineforLymediseasewasmarketedintheUnitedStatesbetween1998and2002,butwaswithdrawnfromthemarketduetopoorsales.[2][26][27]Researchisongoingtodevelopnewvaccines.[2] Contents 1Signsandsymptoms 1.1Earlylocalizedinfection 1.2Earlydisseminatedinfection 1.3Latedisseminatedinfection 2Cause 2.1Ticklifecycle 2.2Transmission 2.3Tick-bornecoinfections 3Pathophysiology 3.1Immunologicalstudies 4Diagnosis 4.1Laboratorytesting 4.2Imaging 4.3Differentialdiagnosis 5Prevention 5.1Tickremoval 5.2Preventiveantibiotics 5.3Gardenlandscaping 5.4Occupationalexposure 5.5Hostanimals 5.6Vaccination 6Treatment 7Prognosis 8Epidemiology 8.1Africa 8.2Asia 8.3Europe 8.3.1UnitedKingdom 8.4NorthAmerica 8.4.1Canada 8.4.2Mexico 8.4.3UnitedStates 8.5SouthAmerica 9History 10Societyandculture 10.1Controversy 11Otheranimals 11.1Pets 12References 13Furtherreading 14Externallinks Signsandsymptoms[edit] Anexpandingrashisaninitialsignofabout80%ofLymeinfections.Therashmaylooklikea"bull'seye",aspictured,inabout80%ofcasesinEuropeand20%ofcasesintheUS.[28][29][30][31] Lymediseasecanaffectmultiplebodysystemsandproduceabroadrangeofsymptoms.NoteveryonewithLymediseasehasallofthesymptoms,andmanyofthesymptomsarenotspecifictoLymediseasebutcanoccurwithotherdiseasesaswell.[32] Theincubationperiodfrominfectiontotheonsetofsymptomsisusuallyonetotwoweeksbutcanbemuchshorter(days),ormuchlonger(monthstoyears).[33]LymesymptomsmostoftenoccurfromMaytoSeptemberinthenorthernhemisphere,becausethenymphalstageofthetickisresponsibleformostcases.[33]Asymptomaticinfectionexistsbutoccursinlessthan7%ofinfectedindividualsintheUnitedStates.[34]AsymptomaticinfectionmaybemuchmorecommonamongthoseinfectedinEurope.[35] Earlylocalizedinfection[edit] Earlylocalizedinfectioncanoccurwhentheinfectionhasnotyetspreadthroughoutthebody.Onlythesitewheretheinfectionhasfirstcomeintocontactwiththeskinisaffected.Theinitialsignofabout80%ofLymeinfectionsisanerythemamigrans(EM)rashatthesiteofatickbite,oftennearskinfolds,suchasthearmpit,groin,orbackoftheknee,onthetrunk,underclothingstraps,orinchildren'shair,ears,orneck.[28][2]Mostpeoplewhogetinfecteddonotrememberseeingatickorabite.Therashappearstypicallyoneortwoweeks(range3–32days)afterthebiteandexpands2–3 cmperdayuptoadiameterof5–70 cm(median16 cm).[28][2][29]Therashisusuallycircularoroval,redorbluish,andmayhaveanelevatedordarkercenter.[2][30][31]Inabout79%ofcasesinEuropebutonly19%ofcasesinendemicareasoftheU.S.,therashgraduallyclearfromthecentertowardtheedges,possiblyforminga"bull'seye"pattern.[29][30][31]Therashmayfeelwarmbutusuallyisnotitchy,israrelytenderorpainful,andtakesuptofourweekstoresolveifuntreated.[2] TheEMrashisoftenaccompaniedbysymptomsofaviral-likeillness,includingfatigue,headache,bodyaches,fever,andchills,butusuallynotnauseaorupper-respiratoryproblems.Thesesymptomsmayalsoappearwithoutarash,orlingeraftertherashdisappears.Lymecanprogresstolaterstageswithoutthesesymptomsorarash.[2] Peoplewithhighfeverformorethantwodaysorwhoseothersymptomsofviral-likeillnessdonotimprovedespiteantibiotictreatmentforLymedisease,orwhohaveabnormallylowlevelsofwhiteorredcellsorplateletsintheblood,shouldbeinvestigatedforpossiblecoinfectionwithothertick-bornediseases,suchasehrlichiosisandbabesiosis.[36] Earlydisseminatedinfection[edit] Withindaystoweeksaftertheonsetoflocalinfection,theBorreliabacteriamayspreadthroughthelymphaticsystemorbloodstream.In10–20%ofuntreatedcases,EMrashesdevelopatsitesacrossthebodythatbearnorelationtotheoriginaltickbite.[28]Transientmusclepainsandjointpainsarealsocommon.[28] Inabout10–15%ofuntreatedpeople,Lymecausesneurologicalproblemsknownasneuroborreliosis.[37]Earlyneuroborreliosistypicallyappears4–6weeks(range1–12weeks)afterthetickbiteandinvolvessomecombinationoflymphocyticmeningitis,cranialneuritis,radiculopathyand/ormononeuritismultiplex.[36][38]Lymphocyticmeningitiscausescharacteristicchangesinthecerebrospinalfluid(CSF)andmaybeaccompaniedforseveralweeksbyvariableheadacheand,lesscommonly,usuallymildmeningitissignssuchasinabilitytoflextheneckfullyandintolerancetobrightlights,buttypicallynooronlyverylowfever.[39]Afterseveralmonths,neuroborreliosiscanalsopresentotolaryngologicalsymptoms.Upto76.5%oftheseotolaryngologicalpresentsastinnitus,themostcommonsymptom.Vertigoanddizziness(53.7%)andhearingloss(16.7%)werethenextmostcommonsymptoms.[40]Inchildren,partiallossofvisionmayalsooccur.[36]Cranialneuritisisaninflammationofcranialnerves.WhenduetoLyme,itmosttypicallycausesfacialpalsyimpairingblinking,smiling,andchewinginoneorbothsidesoftheface.Itmayalsocauseintermittentdoublevision.[36][39]Lymeradiculopathyisaninflammationofspinalnerverootsthatoftencausespainandlessoftenweakness,numbness,oralteredsensationintheareasofthebodyservedbynervesconnectedtotheaffectedroots,e.g.limb(s)orpart(s)oftrunk.Thepainisoftendescribedasunlikeanyotherpreviouslyfelt,excruciating,migrating,worseatnight,rarelysymmetrical,andoftenaccompaniedbyextremesleepdisturbance.[38][41]Mononeuritismultiplexisaninflammationcausingsimilarsymptomsinoneormoreunrelatedperipheralnerves.[37][36]Rarely,earlyneuroborreliosismayinvolveinflammationofthebrainorspinalcord,withsymptomssuchasconfusion,abnormalgait,ocularmovements,orspeech,impairedmovement,impairedmotorplanning,orshaking.[36][38] InNorthAmerica,facialpalsyisthetypicalearlyneuroborreliosispresentation,occurringin5–10%ofuntreatedpeople,inabout75%ofcasesaccompaniedbylymphocyticmeningitis.[36][42]Lymeradiculopathyisreportedhalfasfrequently,butmanycasesmaybeunrecognized.[43]InEuropeanadults,themostcommonpresentationisacombinationoflymphocyticmeningitisandradiculopathyknownasBannwarthsyndrome,accompaniedin36-89%ofcasesbyfacialpalsy.[38][41]Inthissyndrome,radicularpaintendstostartinthesamebodyregionastheinitialerythemamigransrash,iftherewasone,andprecedespossiblefacialpalsyandotherimpairedmovement.[41]Inextremecases,permanentimpairmentofmotororsensoryfunctionofthelowerlimbsmayoccur.[35]InEuropeanchildren,themostcommonmanifestationsarefacialpalsy(in55%),othercranialneuritis,andlymphocyticmeningitis(in27%).[38] Inabout4–10%ofuntreatedcasesintheU.S.and0.3–4%ofuntreatedcasesinEurope,typicallybetweenJuneandDecember,aboutonemonth(range4days-7months)afterthetickbite,theinfectionmaycauseheartcomplicationsknownasLymecarditis.[44][45]Symptomsmayincludeheartpalpitations(in69%ofpeople),dizziness,fainting,shortnessofbreath,andchestpain.[44]OthersymptomsofLymediseasemayalsobepresent,suchasEMrash,jointaches,facialpalsy,headaches,orradicularpain.[44]Insomepeople,however,carditismaybethefirstmanifestationofLymedisease.[44]Lymecarditisin19–87%ofpeopleadverselyimpactstheheart'selectricalconductionsystem,causingatrioventricularblockthatoftenmanifestsasheartrhythmsthatalternatewithinminutesbetweenabnormallyslowandabnormallyfast.[44][45]In10–15%ofpeople,Lymecausesmyocardialcomplicationssuchascardiomegaly,leftventriculardysfunction,orcongestiveheartfailure.[44] Anotherskincondition,foundinEuropebutnotinNorthAmerica,isborreliallymphocytoma,apurplishlumpthatdevelopsontheearlobe,nipple,orscrotum.[46] Latedisseminatedinfection[edit] Afterseveralmonths,untreatedorinadequatelytreatedpeoplemaygoontodevelopchronicsymptomsthataffectmanypartsofthebody,includingthejoints,nerves,brain,eyes,andheart.[citationneeded] Lymearthritisoccursinupto60%ofuntreatedpeople,typicallystartingaboutsixmonthsafterinfection.[28]Itusuallyaffectsonlyoneorafewjoints,oftenakneeorpossiblythehip,otherlargejoints,orthetemporomandibularjoint.[36][47]Thereisusuallylargejointeffusionandswelling,butonlymildormoderatepain.[36]Withouttreatment,swellingandpaintypicallyresolveovertimebutperiodicallyreturn.[36]Baker'scystsmayformandrupture.Insomecases,jointerosionoccurs.[citationneeded] Chronicneurologicsymptomsoccurinupto5%ofuntreatedpeople.[48]Aperipheralneuropathyorpolyneuropathymaydevelop,causingabnormalsensationssuchasnumbness,tinglingorburningstartingatthefeetorhandsandovertimepossiblymovingupthelimbs.Atestmayshowreducedsensationofvibrationsinthefeet.Anaffectedpersonmayfeelasifwearingastockingorglovewithoutactuallydoingso.[36] AneurologicsyndromecalledLymeencephalopathyisassociatedwithsubtlememoryandcognitivedifficulties,insomnia,ageneralsenseoffeelingunwell,andchangesinpersonality.[49]However,problemssuchasdepressionandfibromyalgiaareascommoninpeoplewithLymediseaseasinthegeneralpopulation.[50][51] Lymecancauseachronicencephalomyelitisthatresemblesmultiplesclerosis.Itmaybeprogressiveandcaninvolvecognitiveimpairment,brainfog,migraines,balanceissues,weaknessinthelegs,awkwardgait,facialpalsy,bladderproblems,vertigo,andbackpain.Inrarecases,untreatedLymediseasemaycausefrankpsychosis,whichhasbeenmisdiagnosedasschizophreniaorbipolardisorder.Panicattacksandanxietycanoccur;also,delusionalbehaviormaybeseen,includingsomatoformdelusions,sometimesaccompaniedbyadepersonalizationorderealizationsyndrome,wherethepeoplebegintofeeldetachedfromthemselvesorfromreality.[52][53] Acrodermatitischronicaatrophicans(ACA)isachronicskindisorderobservedprimarilyinEuropeamongtheelderly.[46]ACAbeginsasareddish-bluepatchofdiscoloredskin,oftenonthebacksofthehandsorfeet.Thelesionslowlyatrophiesoverseveralweeksormonths,withtheskinbecomingfirstthinandwrinkledandthen,ifuntreated,completelydryandhairless.[54] Cause[edit] Mainarticle:Lymediseasemicrobiology Deerticklifecycle Borreliabacteria,thecausativeagentofLymedisease,magnified Ixodesscapularis,theprimaryvectorofLymediseaseineasternNorthAmerica TickIxodesricinus,developmentalstages Lymediseaseiscausedbyspirochetes,spiralbacteriafromthegenusBorrelia.Spirochetesaresurroundedbypeptidoglycanandflagella,alongwithanoutermembranesimilartoGram-negativebacteria.Becauseoftheirdouble-membraneenvelope,BorreliabacteriaareoftenmistakenlydescribedasGramnegativedespitetheconsiderabledifferencesintheirenvelopecomponentsfromGram-negativebacteria.[55]TheLyme-relatedBorreliaspeciesarecollectivelyknownasBorreliaburgdorferisensulato,andshowagreatdealofgeneticdiversity.[56] B.burgdorferisensulatoisaspeciescomplexmadeupof20acceptedandthreeproposedgenospecies.EightspeciesareknowntocauseLymedisease:B.mayonii(foundinNorthAmerica),B.burgdorferisensustricto,B.bissettiae(bothfoundinNorthAmericaandEurope),B.afzelii,B.garinii,B.spielmanii,andB.lusitaniae(allfoundinEurasia).[57][58][14][7]SomestudieshavealsoproposedthatB.valaisianamaysometimesinfecthumans,butthisspeciesdoesnotseemtobeimportantcausesofdisease.[59][60] Furtherinformation:WeatherandclimateeffectsonLymediseaseexposure Ticklifecycle[edit] Therearethreestagesinthelifecycleofatick.Larva,nymph,andadult.Duringthenymphstage,ticksmostfrequentlytransmitLymediseaseandareusuallymostactiveinlatespringandearlysummerinregionswheretheclimateismild.Duringtheadultstage,Lymediseasetransmissionislesscommonduetothefactthatitislesspossibleforadulttickstobitehumansandbecausetheytendtobelargerinsizeandthereforecanbeeasilyseenandremoved.[61] Transmission[edit] Lymediseaseisclassifiedasazoonosis,asitistransmittedtohumansfromanaturalreservoiramongsmallmammalsandbirdsbyticksthatfeedonbothsetsofhosts.[62]Hard-bodiedticksofthegenusIxodesarethevectorsofLymedisease(alsothevectorforBabesia).[63]Mostinfectionsarecausedbyticksinthenymphalstage,becausetheyareverysmallandthusmayfeedforlongperiodsoftimeundetected.[62]Nymphalticksaregenerallythesizeofapoppyseedandsometimeswithadarkheadandatranslucentbody.[64]Or,thenymphaltickscanbedarker.[65](Theyoungerlarvalticksareveryrarelyinfected.[66])Althoughdeerarethepreferredhostsofadultdeerticks,andtickpopulationsaremuchlowerintheabsenceofdeer,ticksgenerallydonotacquireBorreliafromdeer,insteadtheyobtainthemfrominfectedsmallmammalssuchasthewhite-footedmouse,andoccasionallybirds.[67]AreaswhereLymeiscommonareexpanding.[68] Withinthetickmidgut,theBorrelia'soutersurfaceproteinA(OspA)bindstothetickreceptorforOspA,knownasTROSPA.Whenthetickfeeds,theBorreliadownregulatesOspAandupregulatesOspC,anothersurfaceprotein.Afterthebacteriamigratefromthemidguttothesalivaryglands,OspCbindstoSalp15,aticksalivaryproteinthatappearstohaveimmunosuppressiveeffectsthatenhanceinfection.[69]SuccessfulinfectionofthemammalianhostdependsonbacterialexpressionofOspC.[70] Tickbitesoftengounnoticedbecauseofthesmallsizeofthetickinitsnymphalstage,aswellasticksecretionsthatpreventthehostfromfeelinganyitchorpainfromthebite.However,transmissionisquiterare,withonlyabout1.2to1.4percentofrecognizedtickbitesresultinginLymedisease.[71] InEurope,themainvectorisIxodesricinus,whichisalsocalledthesheeptickorcastorbeantick.[72]InChina,Ixodespersulcatus(thetaigatick)isprobablythemostimportantvector.[73]InNorthAmerica,theblack-leggedtickordeertick(Ixodesscapularis)isthemainvectorontheEastCoast.[66] Thelonestartick(Amblyommaamericanum),whichisfoundthroughouttheSoutheasternUnitedStatesasfarwestasTexas,isunlikelytotransmittheLymediseasespirochetes,[74]thoughitmaybeimplicatedinarelatedsyndromecalledsoutherntick-associatedrashillness,whichresemblesamildformofLymedisease.[75] OntheWestCoastoftheUnitedStates,themainvectoristhewesternblack-leggedtick(Ixodespacificus).[76]ThetendencyofthistickspeciestofeedpredominantlyonhostspeciessuchastheWesternFenceLizardthatareresistanttoBorreliainfectionappearstodiminishtransmissionofLymediseaseintheWest.[77][78] Transmissioncanoccuracrosstheplacentaduringpregnancyandaswithanumberofotherspirochetaldiseases,adversepregnancyoutcomesarepossiblewithuntreatedinfection;prompttreatmentwithantibioticsreducesoreliminatesthisrisk.[79][80][81][82][83] ThereisnoscientificevidencetosupportLymediseasetransmissionviabloodtransfusion,sexualcontact,orbreastmilk.[84] Tick-bornecoinfections[edit] Mainarticle:Tick-bornedisease TicksthattransmitB.burgdorferitohumanscanalsocarryandtransmitseveralotherparasites,suchasBabesiamicrotiandAnaplasmaphagocytophilum,whichcausethediseasesbabesiosisandhumangranulocyticanaplasmosis(HGA),respectively.[85]AmongpeoplewithearlyLymedisease,dependingontheirlocation,2–12%willalsohaveHGAand2–40%willhavebabesiosis.[86]Ticksincertainregions,includingthelandsalongtheeasternBalticSea,alsotransmitvirusesthatcausetick-borneencephalitis.[87] CoinfectionscomplicateLymesymptoms,especiallydiagnosisandtreatment.ItispossibleforaticktocarryandtransmitoneofthecoinfectionsandnotBorrelia,makingdiagnosisdifficultandoftenelusive.TheCentersforDiseaseControlandPreventionstudied100ticksinruralNewJersey,andfound55%ofthetickswereinfectedwithatleastoneofthepathogens.[88] Pathophysiology[edit] B.burgdorfericanspreadthroughoutthebodyduringthecourseofthedisease,andhasbeenfoundintheskin,heart,joints,peripheralnervoussystem,andcentralnervoussystem.[70][89]ManyofthesignsandsymptomsofLymediseaseareaconsequenceoftheimmuneresponsetospirocheteinthosetissues.[48] B.burgdorferiisinjectedintotheskinbythebiteofaninfectedIxodestick.Ticksaliva,whichaccompaniesthespirocheteintotheskinduringthefeedingprocess,containssubstancesthatdisrupttheimmuneresponseatthesiteofthebite.[90]Thisprovidesaprotectiveenvironmentwherethespirochetecanestablishinfection.Thespirochetesmultiplyandmigrateoutwardwithinthedermis.ThehostinflammatoryresponsetothebacteriaintheskincausesthecharacteristiccircularEMlesion.[70]Neutrophils,however,whicharenecessarytoeliminatethespirochetesfromtheskin,failtoappearinnecessarynumbersinthedevelopingEMlesionbecauseticksalivainhibitsneutrophilfunction.Thisallowsthebacteriatosurviveandeventuallyspreadthroughoutthebody.[91] Daystoweeksfollowingthetickbite,thespirochetesspreadviathebloodstreamtojoints,heart,nervoussystem,anddistantskinsites,wheretheirpresencegivesrisetothevarietyofsymptomsofthedisseminateddisease.ThespreadofB.burgdorferiisaidedbytheattachmentofthehostproteaseplasmintothesurfaceofthespirochete.[92] Ifuntreated,thebacteriamaypersistinthebodyformonthsorevenyears,despitetheproductionofB.burgdorferiantibodiesbytheimmunesystem.[93]Thespirochetesmayavoidtheimmuneresponsebydecreasingexpressionofsurfaceproteinsthataretargetedbyantibodies,antigenicvariationoftheVlsEsurfaceprotein,inactivatingkeyimmunecomponentssuchascomplement,andhidingintheextracellularmatrix,whichmayinterferewiththefunctionofimmunefactors.[94][95] Inthebrain,B.burgdorferimayinduceastrocytestoundergoastrogliosis(proliferationfollowedbyapoptosis),whichmaycontributetoneurodysfunction.[96]Thespirochetesmayalsoinducehostcellstosecretequinolinicacid,whichstimulatestheNMDAreceptoronnervecells,whichmayaccountforthefatigueandmalaiseobservedwithLymeencephalopathy.[97]Inaddition,diffusewhitematterpathologyduringLymeencephalopathymaydisruptgraymatterconnections,andcouldaccountfordeficitsinattention,memory,visuospatialability,complexcognition,andemotionalstatus.Whitematterdiseasemayhaveagreaterpotentialforrecoverythangraymatterdisease,perhapsbecauseneuronallossislesscommon.ResolutionofMRIwhitematterhyperintensitiesafterantibiotictreatmenthasbeenobserved.[98] Tryptophan,aprecursortoserotonin,appearstobereducedwithinthecentralnervoussysteminanumberofinfectiousdiseasesthataffectthebrain,includingLyme.[99]Researchersareinvestigatingifthisneurohormonesecretionisthecauseofneuropsychiatricdisordersdevelopinginsomepeoplewithborreliosis.[100] Immunologicalstudies[edit] ExposuretotheBorreliabacteriumduringLymediseasepossiblycausesalong-livedanddamaginginflammatoryresponse,[101]aformofpathogen-inducedautoimmunedisease.[102]Theproductionofthisreactionmightbeduetoaformofmolecularmimicry,whereBorreliaavoidsbeingkilledbytheimmunesystembyresemblingnormalpartsofthebody'stissues.[103][104] Chronicsymptomsfromanautoimmunereactioncouldexplainwhysomesymptomspersistevenafterthespirocheteshavebeeneliminatedfromthebody.Thishypothesismayexplainwhychronicarthritispersistsafterantibiotictherapy,similartorheumaticfever,butitswiderapplicationiscontroversial.[105][106] Diagnosis[edit] Lymediseaseisdiagnosedbasedonsymptoms,objectivephysicalfindings(suchaserythemamigrans(EM)rash,facialpalsy,orarthritis),historyofpossibleexposuretoinfectedticks,andpossiblylaboratorytests.[2][28]PeoplewithsymptomsofearlyLymediseaseshouldhaveatotalbodyskinexaminationforEMrashesandaskedwhetherEM-typerasheshadmanifestedwithinthelast1–2months.[36]PresenceofanEMrashandrecenttickexposure(i.e.,beingoutdoorsinalikelytickhabitatwhereLymeiscommon,within30daysoftheappearanceoftherash)aresufficientforLymediagnosis;nolaboratoryconfirmationisneededorrecommended.[2][28][107][108]Mostpeoplewhogetinfecteddonotrememberatickorabite,andtheEMrashneednotlooklikeabull'seye(mostEMrashesintheU.S.donot)orbeaccompaniedbyanyothersymptoms.[2][109]IntheU.S.,LymeismostcommonintheNewEnglandandMid-AtlanticstatesandpartsofWisconsinandMinnesota,butitisexpandingintootherareas.[68]SeveralborderingareasofCanadaalsohavehighLymerisk.[110] IntheabsenceofanEMrashorhistoryoftickexposure,Lymediagnosisdependsonlaboratoryconfirmation.[63][111]ThebacteriathatcauseLymediseasearedifficulttoobservedirectlyinbodytissuesandalsodifficultandtootime-consumingtogrowinthelaboratory.[2][63]Themostwidelyusedtestslookinsteadforpresenceofantibodiesagainstthosebacteriaintheblood.[112]Apositiveantibodytestresultdoesnotbyitselfproveactiveinfectionbutcanconfirmaninfectionthatissuspectedbecauseofsymptoms,objectivefindings,andhistoryoftickexposureinaperson.[63]Becauseasmanyas5–20%ofthenormalpopulationhaveantibodiesagainstLyme,peoplewithouthistoryandsymptomssuggestiveofLymediseaseshouldnotbetestedforLymeantibodies:apositiveresultwouldlikelybefalse,possiblycausingunnecessarytreatment.[36][38] Insomecases,whenhistory,signs,andsymptomsarestronglysuggestiveofearlydisseminatedLymedisease,empirictreatmentmaybestartedandreevaluatedaslaboratorytestresultsbecomeavailable.[42][113] Laboratorytesting[edit] TestsforantibodiesinthebloodbyELISAandWesternblotisthemostwidelyusedmethodforLymediagnosis.Atwo-tieredprotocolisrecommendedbytheCentersforDiseaseControlandPrevention(CDC):thesensitiveELISAtestisperformedfirst,andifitispositiveorequivocal,thenthemorespecificWesternblotisrun.[114]Theimmunesystemtakessometimetoproduceantibodiesinquantity.AfterLymeinfectiononset,antibodiesoftypesIgMandIgGusuallycanfirstbedetectedrespectivelyat2–4weeksand4–6weeks,andpeakat6–8weeks.[115]WhenanEMrashfirstappears,detectableantibodiesmaynotbepresent.Therefore,itisrecommendedthattestingnotbeperformedanddiagnosisbebasedonthepresenceoftheEMrash.[36]Upto30daysaftersuspectedLymeinfectiononset,infectioncanbeconfirmedbydetectionofIgMorIgGantibodies;afterthat,itisrecommendedthatonlyIgGantibodiesbeconsidered.[115]ApositiveIgMandnegativeIgGtestresultafterthefirstmonthofinfectionisgenerallyindicativeofafalse-positiveresult.[116]ThenumberofIgMantibodiesusuallycollapses4–6monthsafterinfection,whileIgGantibodiescanremaindetectableforyears.[115] Othertestsmaybeusedinneuroborreliosiscases.InEurope,neuroborreliosisisusuallycausedbyBorreliagariniiandalmostalwaysinvolveslymphocyticpleocytosis,i.e.thedensitiesoflymphocytes(infection-fightingcells)andproteininthecerebrospinalfluid(CSF)typicallyrisetocharacteristicallyabnormallevels,whileglucoselevelremainsnormal.[39][36][41]Additionally,theimmunesystemproducesantibodiesagainstLymeinsidetheintrathecalspace,whichcontainstheCSF.[36][41]DemonstrationbylumbarpunctureandCSFanalysisofpleocytosisandintrathecalantibodyproductionarerequiredfordefinitediagnosisofneuroborreliosisinEurope(exceptincasesofperipheralneuropathyassociatedwithacrodermatitischronicaatrophicans,whichusuallyiscausedbyBorreliaafzeliiandconfirmedbybloodantibodytests).[38]InNorthAmerica,neuroborreliosisiscausedbyBorreliaburgdorferiandmaynotbeaccompaniedbythesameCSFsigns;theyconfirmadiagnosisofcentralnervoussystem(CNS)neuroborreliosisifpositive,butdonotexcludeitifnegative.[117]AmericanguidelinesconsiderCSFanalysisoptionalwhensymptomsappeartobeconfinedtotheperipheralnervoussystem(PNS),e.g.facialpalsywithoutovertmeningitissymptoms.[36][118]Unlikebloodandintrathecalantibodytests,CSFpleocytosistestsreverttonormalafterinfectionendsandthereforecanbeusedasobjectivemarkersoftreatmentsuccessandinformdecisionsonwhethertoretreat.[41]IninfectioninvolvingthePNS,electromyographyandnerveconductionstudiescanbeusedtomonitorobjectivelytheresponsetotreatment.[39] InLymecarditis,electrocardiogramsareusedtoevidenceheartconductionabnormalities,whileechocardiographymayshowmyocardialdysfunction.[44]BiopsyandconfirmationofBorreliacellsinmyocardialtissuemaybeusedinspecificcasesbutareusuallynotdonebecauseofriskoftheprocedure.[44] Polymerasechainreaction(PCR)testsforLymediseasehavealsobeendevelopedtodetectthegeneticmaterial(DNA)oftheLymediseasespirochete.CultureorPCRarethecurrentmeansfordetectingthepresenceoftheorganism,asserologicstudiesonlytestforantibodiesofBorrelia.PCRhastheadvantageofbeingmuchfasterthanculture.However,PCRtestsaresusceptibletofalsepositiveresults,e.g.bydetectionofdebrisofdeadBorreliacellsorspecimencontamination.[119][38]Evenwhenproperlyperformed,PCRoftenshowsfalse-negativeresultsbecausefewBorreliacellscanbefoundinbloodandcerebrospinalfluid(CSF)duringinfection.[120][38]Hence,PCRtestsarerecommendedonlyinspecialcases,e.g.diagnosisofLymearthritis,becauseitisahighlysensitivewayofdetectingospADNAinsynovialfluid.[121]AlthoughsensitivityofPCRinCSFislow,itsusemaybeconsideredwhenintrathecalantibodyproductiontestresultsaresuspectedofbeingfalselynegative,e.g.inveryearly(<6weeks)neuroborreliosisorinimmunosuppressedpeople.[38] SeveralotherformsoflaboratorytestingforLymediseaseareavailable,someofwhichhavenotbeenadequatelyvalidated.OspAantigens,shedbyliveBorreliabacteriaintourine,areapromisingtechniquebeingstudied.[122]TheuseofnanotrapparticlesfortheirdetectionisbeinglookedatandtheOspAhasbeenlinkedtoactivesymptomsofLyme.[123][124]HightitersofeitherimmunoglobulinG(IgG)orimmunoglobulinM(IgM)antibodiestoBorreliaantigensindicatedisease,butlowertiterscanbemisleading,becausetheIgMantibodiesmayremainaftertheinitialinfection,andIgGantibodiesmayremainforyears.[125] TheCDCdoesnotrecommendurineantigentests,PCRtestsonurine,immunofluorescentstainingforcell-wall-deficientformsofB.burgdorferi,andlymphocytetransformationtests.[120] Imaging[edit] Neuroimagingiscontroversialinwhetheritprovidesspecificpatternsuniquetoneuroborreliosis,butmayaidindifferentialdiagnosisandinunderstandingthepathophysiologyofthedisease.[126]Thoughcontroversial,someevidenceshowscertainneuroimagingtestscanprovidedatathatarehelpfulinthediagnosisofaperson.Magneticresonanceimaging(MRI)andsingle-photonemissioncomputedtomography(SPECT)aretwooftheteststhatcanidentifyabnormalitiesinthebrainofapersonaffectedwiththisdisease.NeuroimagingfindingsinanMRIincludelesionsintheperiventricularwhitematter,aswellasenlargedventriclesandcorticalatrophy.Thefindingsareconsideredsomewhatunexceptionalbecausethelesionshavebeenfoundtobereversiblefollowingantibiotictreatment.ImagesproducedusingSPECTshownumerousareaswhereaninsufficientamountofbloodisbeingdeliveredtothecortexandsubcorticalwhitematter.However,SPECTimagesareknowntobenonspecificbecausetheyshowaheterogeneouspatternintheimaging.TheabnormalitiesseenintheSPECTimagesareverysimilartothoseseeninpeoplewithcerebralvacuitiesandCreutzfeldt–Jakobdisease,whichmakesthemquestionable.[127] Differentialdiagnosis[edit] Communityclinicshavebeenreportedtomisdiagnose23–28%ofErythemamigrans(EM)rashesand83%ofotherobjectivemanifestationsofearlyLymedisease.[111]EMrashesareoftenmisdiagnosedasspiderbites,cellulitis,orshingles.[111]ManymisdiagnosesarecreditedtothewidespreadmisconceptionthatEMrashesshouldlooklikeabull'seye.[2]Actually,thekeydistinguishingfeaturesoftheEMrasharethespeedandextenttowhichitexpands,respectivelyupto2–3 cm/dayandadiameterofatleast5 cm,andin50%ofcasesmorethan16 cm.Therashexpandsawayfromitscenter,whichmayormaynotlookdifferentorbeseparatedbyring-likeclearingfromtherestoftherash.[28][29]ComparedtoEMrashes,spiderbitesaremorecommoninthelimbs,tendtobemorepainfulanditchyorbecomeswollen,andsomemaycausenecrosis(sinkingdarkbluepatchofdeadskin).[28][2]Cellulitismostcommonlydevelopsaroundawoundorulcer,israrelycircular,andismorelikelytobecomeswollenandtender.[28][2]EMrashesoftenappearatsitesthatareunusualforcellulitis,suchasthearmpit,groin,abdomen,orbackofknee.[28]LikeLyme,shinglesoftenbeginswithheadache,fever,andfatigue,whicharefollowedbypainornumbness.However,unlikeLyme,inshinglesthesesymptomsareusuallyfollowedbyappearanceofrashescomposedofmultiplesmallblistersalongwithanerve'sdermatome,andshinglescanalsobeconfirmedbyquicklaboratorytests.[128] FacialpalsycausedbyLymedisease(LDFP)isoftenmisdiagnosedasBell'spalsy.[42]AlthoughBell'spalsyisthemostcommontypeofone-sidedfacialpalsy(about70%ofcases),LDFPcanaccountforabout25%ofcasesoffacialpalsyinareaswhereLymediseaseiscommon.[42]ComparedtoLDFP,Bell'spalsymuchlessfrequentlyaffectsbothsidesoftheface.[42]EventhoughLDFPandBell'spalsyhavesimilarsymptomsandevolvesimilarlyifuntreated,corticosteroidtreatmentisbeneficialforBell'sPalsy,whilebeingdetrimentalforLDFP.[42]Recenthistoryofexposuretoalikelytickhabitatduringwarmermonths,EMrash,viral-likesymptomssuchasheadacheandfever,and/orpalsyinbothsidesofthefaceshouldbeevaluatedforthelikelihoodofLDFP;ifitismorethanminimal,empirictherapywithantibioticsshouldbeinitiated,withoutcorticosteroids,andreevaluateduponcompletionoflaboratorytestsforLymedisease.[42] Unlikeviralmeningitis,Lymelymphocyticmeningitistendstonotcausefever,lastlonger,andrecur.[39][36]Lymphocyticmeningitisisalsocharacterizedbypossiblyco-occurringwithEMrash,facialpalsy,orpartialvisionobstructionandhavingmuchlowerpercentageofpolymorphonuclearleukocytesinCSF.[36] Lymeradiculopathyaffectingthelimbsisoftenmisdiagnosedasaradiculopathycausedbynerverootcompression,suchassciatica.[111][129]Althoughmostcasesofradiculopathyarecompressiveandresolvewithconservativetreatment(e.g.,rest)within4–6weeks,guidelinesformanagingradiculopathyrecommendfirstevaluatingrisksofotherpossiblecausesthat,althoughlessfrequent,requireimmediatediagnosisandtreatment,includinginfectionssuchasLymeandshingles.[130]Ahistoryofoutdooractivitiesinlikelytickhabitatsinthelast3monthspossiblyfollowedbyarashorviral-likesymptoms,andcurrentheadache,othersymptomsoflymphocyticmeningitis,orfacialpalsywouldleadtosuspicionofLymediseaseandrecommendationofserologicalandlumbarpuncturetestsforconfirmation.[130] Lymeradiculopathyaffectingthetrunkcanbemisdiagnosedasmyriadotherconditions,suchasdiverticulitisandacutecoronarysyndrome.[43][111]Diagnosisoflate-stageLymediseaseisoftencomplicatedbyamultifacetedappearanceandnonspecificsymptoms,promptingonereviewertocallLymethenew"greatimitator".[131]Lymediseasemaybemisdiagnosedasmultiplesclerosis,rheumatoidarthritis,fibromyalgia,chronicfatiguesyndrome,lupus,Crohn'sdisease,HIV,orotherautoimmuneandneurodegenerativediseases.Asallpeoplewithlater-stageinfectionwillhaveapositiveantibodytest,simplebloodtestscanexcludeLymediseaseasapossiblecauseofaperson'ssymptoms.[132] Prevention[edit] Tickbitesmaybepreventedbyavoidingorreducingtimeinlikelytickhabitatsandtakingprecautionswhileinandwhengettingoutofone.[133][6] MostLymehumaninfectionsarecausedbyIxodesnymphbitesbetweenAprilandSeptember.[28][133]Ticksprefermoist,shadedlocationsinwoodlands,shrubs,tallgrassesandleaflitterorwoodpiles.[28][134]Tickdensitiestendtobehighestinwoodlands,followedbyunmaintainededgesbetweenwoodsandlawns(abouthalfashigh),ornamentalplantsandperennialgroundcover(aboutaquarter),andlawns(about30timesless).[135]Ixodeslarvaeandnymphstendtobeabundantalsowheremicenest,suchasstonewallsandwoodlogs.[135]Ixodeslarvaeandnymphstypicallywaitforpotentialhosts("quest")onleavesorgrassesclosetothegroundwithforelegsoutstretched;whenahostbrushesagainstitslimbs,thetickrapidlyclingsandclimbsonthehostlookingforaskinlocationtobite.[136]InNortheasternUnitedStates,69%oftickbitesareestimatedtohappeninresidences,11%inschoolsorcamps,9%inparksorrecreationalareas,4%atwork,3%whilehunting,and4%inotherareas.[135]Activitiesassociatedwithtickbitesaroundresidencesincludeyardwork,brushclearing,gardening,playingintheyard,andlettingintothehousedogsorcatsthatroamoutsideinwoodyorgrassyareas.[135][133]Inparks,tickbitesoftenhappenwhilehikingorcamping.[135]Walkingonamowedlawnorcenterofatrailwithouttouchingadjacentvegetationislessriskythancrawlingorsittingonalogorstonewall.[135][137]Petsshouldnotbeallowedtoroamfreelyinlikelytickhabitats.[134] Asaprecaution,CDCrecommendssoakingorsprayingclothes,shoes,andcampinggearsuchastents,backpacksandsleepingbagswith0.5%permethrinsolutionandhangingthemtodrybeforeuse.[133][138]Permethrinisodorlessandsafeforhumansbuthighlytoxictoticks.[139]Aftercrawlingonpermethrin-treatedfabricforasfewas10–20seconds,ticknymphsbecomeirritatedandfalloffordie.[139][140]Permethrin-treatedclosed-toedshoesandsocksreduceby74timesthenumberofbitesfromnymphsthatmakefirstcontactwithashoeofapersonalsowearingtreatedshorts(becausenymphsusuallyquestneartheground,thisisatypicalcontactscenario).[139]Betterprotectioncanbeachievedbytuckingpermethrin-treatedtrousers(pants)intotreatedsocksandatreatedlong-sleeveshirtintothetrouserssoastominimizegapsthroughwhichatickmightreachthewearer'sskin.[137]Light-coloredclothingmaymakeiteasiertoseeticksandremovethembeforetheybite.[137]Militaryandoutdoorworkers'uniformstreatedwithpermethrinhavebeenfoundtoreducethenumberofbitecasesby80–95%.[140]Permethrinprotectionlastsseveralweeksofwearandwashingsincustomer-treateditemsandupto70washingsforfactory-treateditems.[138]Permethrinshouldnotbeusedonhumanskin,underwearorcats.[138][141] TheEPArecommendsseveraltickrepellentsforuseonexposedskin,includingDEET,picaridin,IR3535(aderivativeofaminoacidbeta-alanine),oiloflemoneucalyptus(OLE,anaturalcompound)andOLE'sactiveingredientpara-menthane-diol(PMD).[133][142][143]Unlikepermethrin,repellentsrepelbutdonotkillticks,protectforonlyseveralhoursafterapplication,andmaybewashedoffbysweatorwater.[138]ThemostpopularrepellentisDEETintheU.S.andpicaridininEurope.[143]UnlikeDEET,picaridinisodorlessandislesslikelytoirritatetheskinorharmfabricorplastics.[143]Repellentswithhigherconcentrationmaylastlongerbutarenotmoreeffective;againstticks,20%picaridinmayworkfor8hoursvs.55–98.11%DEETfor5–6hoursor30–40%OLEfor6hours.[138][142]Repellentsshouldnotbeusedunderclothes,oneyes,mouth,woundsorcuts,oronbabiesyoungerthan2months(3yearsforOLEorPMD).[138][133]Ifsunscreenisused,repellentshouldbeappliedontopofit.[138]Repellentsshouldnotbesprayeddirectlyonaface,butshouldinsteadbesprayedonahandandthenrubbedontheface.[138] Aftercomingindoors,clothes,gearandpetsshouldbecheckedforticks.[133]Clothescanbeputintoahotdryerfor10minutestokillticks(justwashingorwarmdryerarenotenough).[133]Showeringassoonaspossible,lookingforticksovertheentirebody,andremovingthemreduceriskofinfection.[133]Unfedticknymphsarethesizeofapoppyseed,butadayortwoafterbitingandattachingthemselvestoaperson,theylooklikeasmallbloodblister.[144]Thefollowingareasshouldbecheckedespeciallycarefully:armpits,betweenlegs,backofknee,bellybutton,trunk,andinchildrenears,neckandhair.[133] Tickremoval[edit] Removalofatickusingtweezers Attachedticksshouldberemovedpromptly.Riskofinfectionincreaseswithtimeofattachment,butinNorthAmericariskofLymediseaseissmallifthetickisremovedwithin36hours.[145]CDCrecommendsinsertingafine-tippedtweezerbetweentheskinandthetick,graspingveryfirmly,andpullingtheclosedtweezerstraightawayfromtheskinwithouttwisting,jerking,squeezingorcrushingthetick.[146]Aftertickremoval,anytickpartsremainingintheskinshouldberemovedwithacleantweezer,ifpossible.[146]Thewoundandhandsshouldthenbecleanedwithalcoholorsoapandwater.[146]Thetickmaybedisposedbyplacingitinacontainerwithalcohol,sealedbag,tapeorflusheddownthetoilet.[146]Thebittenpersonshouldwritedownwhereandwhenthebitehappenedsothatthiscanbeinformedtoadoctorifthepersongetsarashorflu-likesymptomsinthefollowingseveralweeks.[146]CDCrecommendsnotusingfingers,nailpolish,petroleumjellyorheatontheticktotrytoremoveit.[146] InAustralia,wheretheAustralianparalysistickisprevalent,theAustralasianSocietyofClinicalImmunologyandAllergyrecommendsnotusingtweezerstoremoveticks,becauseifthepersonisallergic,anaphylaxiscouldresult.[147]Instead,aproductshouldbesprayedontheticktocauseittofreezeandthendropoff.[147]Adoctorwoulduseliquidnitrogen,butproductsavailablefromchemistsforfreezingwartscanbeusedinstead.[148]AnothermethodoriginatingfromAustraliaconsistsinusingabout20 cmofdentalflossorfishinglineforslowlytyinganoverhandknotbetweentheskinandthetickandthenpullingitawayfromtheskin.[149][150] Preventiveantibiotics[edit] Theriskofinfectioustransmissionincreaseswiththedurationoftickattachment.[28]Itrequiresbetween36and48hoursofattachmentforthebacteriathatcausesLymetotravelfromwithinthetickintoitssaliva.[28]IfadeertickthatissufficientlylikelytobecarryingBorreliaisfoundattachedtoapersonandremoved,andifthetickhasbeenattachedfor36hoursorisengorged,asingledoseofdoxycyclineadministeredwithinthe72hoursafterremovalmayreducetheriskofLymedisease.Itisnotgenerallyrecommendedforallpeoplebitten,asdevelopmentofinfectionisrare:about50bittenpeoplewouldhavetobetreatedthiswaytopreventonecaseoferythemamigrans(i.e.thetypicalrashfoundinabout70–80%ofpeopleinfected).[2][28] Gardenlandscaping[edit] Severallandscapingpracticesmayreduceriskoftickbitesinresidentialyards.[144][151]Thelawnshouldbekeptmowed,leaflitterandweedsremovedandgroundcoveruseavoided.[144]Woodlands,shrubs,stonewallsandwoodpilesshouldbeseparatedfromthelawnbya3-ft-widerockorwoodchipbarrier.[151]Withoutvegetationonthebarrier,tickswilltendnottocrossit;acaricidesmayalsobesprayedonittokillticks.[151]Asun-exposedtick-safezoneatleast9 ftfromthebarriershouldconcentratehumanactivityontheyard,includinganypatios,playgroundsandgardening.[151]Materialssuchaswooddecking,concrete,bricks,gravelorwoodchipsmaybeusedonthegroundunderpatiosandplaygroundssoastodiscourageticksthere.[144]An8-ft-highfencemaybeaddedtokeepdeerawayfromthetick-safezone.[151][144] Occupationalexposure[edit] OutdoorworkersareatriskofLymediseaseiftheyworkatsiteswithinfectedticks.Thisincludesconstruction,landscaping,forestry,brushclearing,landsurveying,farming,railroadwork,oilfieldwork,utilitylinework,parkorwildlifemanagement.[152][153]U.S.workersinthenortheasternandnorth-centralstatesareathighestriskofexposuretoinfectedticks.Ticksmayalsotransmitothertick-bornediseasestoworkersintheseandotherregionsofthecountry.Worksiteswithwoods,bushes,highgrassorleaflitterarelikelytohavemoreticks.Outdoorworkersshouldbemostcarefultoprotectthemselvesinthelatespringandsummerwhenyoungticksaremostactive.[154] Hostanimals[edit] Lymeandotherdeertick-bornediseasescansometimesbereducedbygreatlyreducingthedeerpopulationonwhichtheadultticksdependforfeedingandreproduction.Lymediseasecasesfellfollowingdeereradicationonanisland,Monhegan,Maine,[155]andfollowingdeercontrolinMumfordCove,Connecticut.[156]Itisworthnotingthateliminatingdeermayleadtoatemporaryincreaseintickdensity.[157] Forexample,intheU.S.,reducingthedeerpopulationtolevelsof8to10persquaremile(fromthecurrentlevelsof60ormoredeerpersquaremileintheareasofthecountrywiththehighestLymediseaserates)mayreduceticknumbersandreducethespreadofLymeandothertick-bornediseases.[158]However,suchadrasticreductionmaybeverydifficulttoimplementinmanyareas,andlowtomoderatedensitiesofdeerorotherlargemammalhostsmaycontinuetofeedsufficientadulttickstomaintainlarvaldensitiesathighlevels.Routineveterinarycontrolofticksofdomesticanimals,includinglivestock,byuseofacaricidescancontributetoreducingexposureofhumanstoticks.[citationneeded] InEurope,knownreservoirsofBorreliaburgdorferiwere9smallmammals,7medium-sizedmammalsand16speciesofbirds(includingpasserines,sea-birdsandpheasants).[159]TheseanimalsseemtotransmitspirochetestoticksandthusparticipateinthenaturalcirculationofB.burgdorferiinEurope.Thehousemouseisalsosuspectedaswellasotherspeciesofsmallrodents,particularlyinEasternEuropeandRussia.[159]"ThereservoirspeciesthatcontainthemostpathogensaretheEuropeanroedeerCapreoluscapreolus;[160]"itdoesnotappeartoserveasamajorreservoirofB.burgdorferi"thoughtJaenson&al.(1992)[161](incompetenthostforB.burgdorferiandTBEvirus)butitisimportantforfeedingtheticks,[162]asreddeerandwildboars(Susscrofa),[163]inwhichoneRickettsiaandthreeBorreliaspecieswereidentified",[160]withhighrisksofcoinfectioninroedeer.[164]Nevertheless,inthe2000s,inroedeerinEurope"twospeciesofRickettsiaandtwospeciesofBorreliawereidentified".[163] Vaccination[edit] ArecombinantvaccineagainstLymedisease,basedontheoutersurfaceproteinA(ospA)ofB.burgdorferi,wasdevelopedbySmithKlineBeecham.Inclinicaltrialsinvolvingmorethan10,000people,thevaccine,calledLYMErix,wasfoundtoconferprotectiveimmunitytoBorreliain76%ofadultsand100%ofchildrenwithonlymildormoderateandtransientadverseeffects.[165]LYMErixwasapprovedonthebasisofthesetrialsbytheFoodandDrugAdministration(FDA)on21December1998.[166] Followingapprovalofthevaccine,itsentryintoclinicalpracticewasslowforavarietyofreasons,includingitscost,whichwasoftennotreimbursedbyinsurancecompanies.[167]Subsequently,hundredsofvaccinerecipientsreportedtheyhaddevelopedautoimmuneandothersideeffects.Supportedbysomeadvocacygroups,anumberofclass-actionlawsuitswerefiledagainstGlaxoSmithKline,allegingthevaccinehadcausedthesehealthproblems.TheseclaimswereinvestigatedbytheFDAandtheCentersforDiseaseControl,whichfoundnoconnectionbetweenthevaccineandtheautoimmunecomplaints.[168] Despitethelackofevidencethatthecomplaintswerecausedbythevaccine,salesplummetedandLYMErixwaswithdrawnfromtheU.S.marketbyGlaxoSmithKlineinFebruary2002,[169]inthesettingofnegativemediacoverageandfearsofvaccinesideeffects.[168][170]ThefateofLYMErixwasdescribedinthemedicalliteratureasa"cautionarytale";[170]aneditorialinNaturecitedthewithdrawalofLYMErixasaninstanceinwhich"unfoundedpublicfearsplacepressuresonvaccinedevelopersthatgobeyondreasonablesafetyconsiderations."[26]TheoriginaldeveloperoftheOspAvaccineattheMaxPlanckInstitutetoldNature:"Thisjustshowshowirrationaltheworldcanbe ...TherewasnoscientificjustificationforthefirstOspAvaccineLYMErixbeingpulled."[168] VaccineshavebeenformulatedandapprovedforthepreventionofLymediseaseindogs.Currently,threeLymediseasevaccinesareavailable.LymeVax,formulatedbyFortDodgeLaboratories,containsintactdeadspirocheteswhichexposethehosttotheorganism.GalaxyLyme,Intervet-Schering-Plough'svaccine,targetsproteinsOspCandOspA.TheOspCantibodieskillanyofthebacteriathathavenotbeenkilledbytheOspAantibodies.CanineRecombinantLyme,formulatedbyMerial,generatesantibodiesagainsttheOspAproteinsoatickfeedingonavaccinateddogdrawsinbloodfullofanti-OspAantibodies,whichkillthespirochetesinthetick'sgutbeforetheyaretransmittedtothedog.[171] Ahexavalent(OspA)proteinsubunit-basedvaccinecandidateVLA15developedbyValnevawasgrantedfasttrackdesignationbytheU.S.FoodandDrugAdministrationin2017whichwillallowfurtherstudy.[172][173] AmRNAvaccinedesignedtocauseastrongfastimmuneresponsetoticksalivaallowedtodetectandremovetheticksfromtestanimalsbeforetheywereabletotransmittheinfectiousbacteria.[174]ThevaccinecontainsmRNAsforthebodytobuild19proteinsinticksalivawhich,byenablingquickdevelopmentoferythema(itchyredness)atthebitesite,protectsguineapigsagainstLymedisease.Italsoprotectedthetestanimalsifthetickisnotremovedifonlyonetick,butnotthree,remainattached.[175][176] Treatment[edit] Antibioticsaretheprimarytreatment.[2][28]Thespecificapproachtotheiruseisdependentontheindividualaffectedandthestageofthedisease.[28]Formostpeoplewithearlylocalizedinfection,oraladministrationofdoxycyclineiswidelyrecommendedasthefirstchoice,asitiseffectiveagainstnotonlyBorreliabacteriabutalsoavarietyofotherillnessescarriedbyticks.[28]Peopletakingdoxycyclineshouldavoidsunexposurebecauseofhigherriskofsunburns.[36]Doxycyclineiscontraindicatedinchildrenyoungerthaneightyearsofageandwomenwhoarepregnantorbreastfeeding;[28]alternativestodoxycyclineareamoxicillin,cefuroximeaxetil,andazithromycin.[28]Azithromycinisrecommendedonlyincaseofintolerancetotheotherantibiotics.[36]Thestandardtreatmentforcellulitis,cephalexin,isnotusefulforLymedisease.[36]WhenitisunclearifarashiscausedbyLymeorcellulitis,theIDSArecommendstreatmentwithcefuroximeoramoxicillin/clavulanicacid,astheseareeffectiveagainstbothinfections.[36]IndividualswithearlydisseminatedorlateLymeinfectionmayhavesymptomaticcardiacdisease,Lymearthritis,orneurologicsymptomslikefacialpalsy,radiculopathy,meningitis,orperipheralneuropathy.[28]Intravenousadministrationofceftriaxoneisrecommendedasthefirstchoiceinthesecases;[28]cefotaximeanddoxycyclineareavailableasalternatives.[28] TreatmentregimensforLymediseaserangefrom14daysinearlylocalizeddisease,to14–21daysinearlydisseminateddiseaseto14–28daysinlatedisseminateddisease.[177]NeurologiccomplicationsofLymediseasemaybetreatedwithdoxycyclineasitcanbetakenbymouthandhasalowercost,althoughinNorthAmericaevidenceofefficacyisonlyindirect.[118]Incaseoffailure,guidelinesrecommendretreatmentwithinjectableceftriaxone.[118]SeveralmonthsaftertreatmentforLymearthritis,ifjointswellingpersistsorreturns,asecondroundofantibioticsmaybeconsidered;intravenousantibioticsarepreferredforretreatmentincaseofpoorresponsetooralantibiotics.[28][36]Outsideofthat,aprolongedantibioticregimenlastingmorethan28daysisnotrecommendedasnoevidenceshowsittobeeffective.[28][178]IgMandIgGantibodylevelsmaybeelevatedforyearsevenaftersuccessfultreatmentwithantibiotics.[28]Asantibodylevelsarenotindicativeoftreatmentsuccess,testingforthemisnotrecommended.[28] Facialpalsymayresolvewithouttreatment;however,antibiotictreatmentisrecommendedtostopotherLymecomplications.[36]CorticosteroidsarenotrecommendedwhenfacialpalsyiscausedbyLymedisease.[42]Inthosewithfacialpalsy,frequentuseofartificialtearswhileawakeisrecommended,alongwithointmentandapatchortapingtheeyeclosedwhensleeping.[42][179] AboutathirdofpeoplewithLymecarditisneedatemporarypacemakeruntiltheirheartconductionabnormalityresolves,and21%needtobehospitalized.[44]Lymecarditisshouldnotbetreatedwithcorticosteroids.[44] PeoplewithLymearthritisshouldlimittheirlevelofphysicalactivitytoavoiddamagingaffectedjoints,andincaseoflimpingshouldusecrutches.[180]PainassociatedwithLymediseasemaybetreatedwithnonsteroidalanti-inflammatorydrugs(NSAIDs).[36]CorticosteroidjointinjectionsarenotrecommendedforLymearthritisthatisbeingtreatedwithantibiotics.[36][180]PeoplewithLymearthritistreatedwithintravenousantibioticsortwomonthsoforalantibioticswhocontinuetohavejointswellingtwomonthsaftertreatmentandhavenegativePCRtestforBorreliaDNAinthesynovialfluidaresaidtohaveantibiotic-refractoryLymearthritis;thisismorecommonafterinfectionbycertainBorreliastrainsinpeoplewithcertaingeneticandimmunologiccharacteristics.[36][180]Antibiotic-refractoryLymearthritismaybesymptomaticallytreatedwithNSAIDs,disease-modifyingantirheumaticdrugs(DMARDs),orarthroscopicsynovectomy.[36]PhysicaltherapyisrecommendedforadultsafterresolutionofLymearthritis.[180] Peoplereceivingtreatmentshouldbeadvisedthatreinfectionispossibleandhowtopreventit.[113] Prognosis[edit] Lymedisease'stypicalfirstsign,theerythemamigrans(EM)rash,resolveswithinseveralweeksevenwithouttreatment.[2]However,inuntreatedpeople,theinfectionoftendisseminatestothenervoussystem,heart,orjoints,possiblycausingpermanentdamagetobodytissues.[36] PeoplewhoreceiverecommendedantibiotictreatmentwithinseveraldaysofappearanceofaninitialEMrashhavethebestprospects.[111]Recoverymaynotbetotalorimmediate.ThepercentageofpeopleachievingfullrecoveryintheUnitedStatesincreasesfromabout64–71%atendoftreatmentforEMrashtoabout84–90%after30months;higherpercentagesarereportedinEurope.[181][182]Treatmentfailure,i.e.persistenceoforiginalorappearanceofnewsignsofthedisease,occursonlyinafewpeople.[181]Remainingpeopleareconsideredcuredbutcontinuetoexperiencesubjectivesymptoms,e.g.jointormusclepainsorfatigue.[183]Thesesymptomsusuallyaremildandnondisabling.[183] Peopletreatedonlyafternervoussystemmanifestationsofthediseasemayendupwithobjectiveneurologicaldeficits,inadditiontosubjectivesymptoms.[36]InEurope,anaverageof32–33monthsafterinitialLymesymptomsinpeopletreatedmostlywithdoxycycline200 mgfor14–21days,thepercentageofpeoplewithlingeringsymptomswasmuchhigheramongthosediagnosedwithneuroborreliosis(50%)thanamongthosewithonlyanEMrash(16%).[184]InanotherEuropeanstudy,5yearsaftertreatmentforneuroborreliosis,lingeringsymptomswerelesscommonamongchildren(15%)thanadults(30%),andinthelatterwaslesscommonamongthosetreatedwithin30daysofthefirstsymptom(16%)thanamongthosetreatedlater(39%);amongthosewithlingeringsymptoms,54%haddailyactivitiesrestrictedand19%wereonsickleaveorincapacitated.[185] Somedatasuggestthatabout90%ofLymefacialpalsiestreatedwithantibioticsrecoverfullyamedianof24daysafterappearingandmostoftherestrecoverwithonlymildabnormality.[186][187]However,inEurope41%ofpeopletreatedforfacialpalsyhadotherlingeringsymptomsatfollowupupto6monthslater,including28%withnumbnessoralteredsensationand14%withfatigueorconcentrationproblems.[187]Palsiesinbothsidesofthefaceareassociatedwithworseandlongertimetorecovery.[186][187]Historicaldatasuggeststhatuntreatedpeoplewithfacialpalsiesrecoveratnearlythesamerate,but88%subsequentlyhaveLymearthritis.[186][188]Otherresearchshowsthatsynkinesis(involuntarymovementofafacialmusclewhenanotheroneisvoluntarilymoved)canbecomeevidentonly6–12monthsafterfacialpalsyappearstoberesolved,asdamagednervesregrowandsometimesconnecttoincorrectmuscles.[189]Synkinesisisassociatedwithcorticosteroiduse.[189]Inlonger-termfollow-up,16–23%ofLymefacialpalsiesdonotfullyrecover.[189] InEurope,aboutaquarterofpeoplewithBannwarthsyndrome(Lymeradiculopathyandlymphocyticmeningitis)treatedwithintravenousceftriaxonefor14daysanaverageof30daysafterfirstsymptomshadtoberetreated3–6monthslaterbecauseofunsatisfactoryclinicalresponseorcontinuedobjectivemarkersofinfectionincerebrospinalfluid;after12months,64%recoveredfully,31%hadnondisablingmildorinfrequentsymptomsthatdidnotrequireregularuseofanalgesics,and5%hadsymptomsthatweredisablingorrequiredsubstantialuseofanalgesics.[41]Themostcommonlingeringnondisablingsymptomswereheadache,fatigue,alteredsensation,jointpains,memorydisturbances,malaise,radicularpain,sleepdisturbances,musclepains,andconcentrationdisturbances.Lingeringdisablingsymptomsincludedfacialpalsyandotherimpairedmovement.[41] Recoveryfromlateneuroborreliosistendstotakelongerandbelesscompletethanfromearlyneuroborreliosis,probablybecauseofirreversibleneurologicdamage.[36] AbouthalfthepeoplewithLymecarditisprogresstocompleteheartblock,butitusuallyresolvesinaweek.[44]OtherLymeheartconductionabnormalitiesresolvetypicallywithin6weeks.[44]About94%ofpeoplehavefullrecovery,but5%needapermanentpacemakerand1%endupwithpersistentheartblock(theactualpercentagemaybehigherbecauseofunrecognizedcases).[44]Lymemyocardialcomplicationsusuallyaremildandself-limiting.[44]However,insomecasesLymecarditiscanbefatal.[44] Recommendedantibiotictreatmentsareeffectiveinabout90%ofLymearthritiscases,althoughitcantakeseveralmonthsforinflammationtoresolveandasecondroundofantibioticsisoftennecessary.[36]Antibiotic-refractoryLymearthritisalsoeventuallyresolves,typicallywithin9–14months(range4months–4years);DMARDsorsynovectomycanacceleraterecovery.[180] Reinfectionisnotuncommon.InaU.S.study,6–11%ofpeopletreatedforanEMrashhadanotherEMrashwithin30months.[181]ThesecondrashtypicallyisduetoinfectionbyadifferentBorreliastrain.[190] Peoplewhohavenonspecific,subjectivesymptomssuchasfatigue,jointandmuscleaches,orcognitivedifficultiesformorethansixmonthsafterrecommendedtreatmentforLymediseasearesaidtohavepost-treatmentLymediseasesyndrome(PTLDS).Asof2016thereasonforthelingeringsymptomswasnotknown;theconditionisgenerallymanagedsimilarlytofibromyalgiaorchronicfatiguesyndrome.[191] Epidemiology[edit] CountrieswithreportedLymediseasecases. LymediseaseoccursregularlyinNorthernHemispheretemperateregions.[192] Africa[edit] InnorthernAfrica,B.burgdorferisensulatohasbeenidentifiedinMorocco,Algeria,EgyptandTunisia.[193][194][195] Lymediseaseinsub-SaharanAfricaispresentlyunknown,butevidenceindicatesitmayoccurinhumansinthisregion.TheabundanceofhostsandtickvectorswouldfavortheestablishmentofLymeinfectioninAfrica.[196]InEastAfrica,twocasesofLymediseasehavebeenreportedinKenya.[197] Asia[edit] B.burgdorferisensulato-infestedticksarebeingfoundmorefrequentlyinJapan,aswellasinnorthwestChina,Nepal,ThailandandfareasternRussia.[198][199]BorreliahasalsobeenisolatedinMongolia.[200] Europe[edit] InEurope,LymediseaseiscausedbyinfectionwithoneormorepathogenicEuropeangenospeciesofthespirochaeteB.burgdorferisensulato,mainlytransmittedbythetickIxodesricinus.[201]CasesofB.burgdorferisensulato-infectedticksarefoundpredominantlyincentralEurope,particularlyinSloveniaandAustria,buthavebeenisolatedinalmosteverycountryonthecontinent.[202]NumberofcasesinsouthernEurope,suchasItalyandPortugal,ismuchlower.[203]DiagnosedcasesinsomeWesternCountries,suchasIceland,arerising.[204] UnitedKingdom[edit] IntheUnitedKingdomthenumberoflaboratoryconfirmedcasesofLymediseasehasbeenrisingsteadilysincevoluntaryreportingwasintroducedin1986[205]when68caseswererecordedintheUKandIrelandcombined.[206]IntheUKtherewere23confirmedcasesin1988and19in1990,[207]but973in2009[205]and953in2010.[208]Provisionalfiguresforthefirst3quartersof2011showa26%increaseonthesameperiodin2010.[209] Itisthought,however,thattheactualnumberofcasesissignificantlyhigherthansuggestedbytheabovefigures,withtheUK'sHealthProtectionAgencyestimatingthattherearebetween2,000and3,000casesperyear,[208](withanaverageofaround15%oftheinfectionsacquiredoverseas[205]),whileDrDarrelHo-Yen,DirectoroftheScottishToxoplasmaReferenceLaboratoryandNationalLymeDiseaseTestingService,believesthatthenumberofconfirmedcasesshouldbemultipliedby10"totakeaccountofwronglydiagnosedcases,testsgivingfalseresults,suffererswhoweren'ttested,peoplewhoareinfectedbutnotshowingsymptoms,failurestonotifyandinfectedindividualswhodon'tconsultadoctor."[210][211] DespiteLymedisease(Borreliaburgdorferiinfection)beinganotifiablediseaseinScotland[212]sinceJanuary1990[213]whichshouldthereforebereportedonthebasisofclinicalsuspicion,itisbelievedthatmanyGPsareunawareoftherequirement.[214]Mandatoryreporting,limitedtolaboratorytestresultsonly,wasintroducedthroughouttheUKinOctober2010,undertheHealthProtection(Notification)Regulations2010.[205] AlthoughthereisagreaternumberofcasesofLymediseaseintheNewForest,SalisburyPlain,Exmoor,theSouthDowns,partsofWiltshireandBerkshire,ThetfordForest[215]andtheWestcoastandislandsofScotland,[216]infectedticksarewidespread,andcanevenbefoundintheparksofLondon.[207][217]A1989reportfoundthat25%offorestryworkersintheNewForestwereseropositive,aswerebetween2%and4–5%ofthegenerallocalpopulationofthearea.[218][219] Testsonpetdogscarriedoutthroughoutthecountryin2009indicatedthataround2.5%ofticksintheUKmaybeinfected,considerablyhigherthanpreviouslythought.[220][221]Itisthoughtthatglobalwarmingmayleadtoanincreaseintickactivityinthefuture,aswellasanincreaseintheamountoftimethatpeoplespendinpublicparks,thusincreasingtheriskofinfection.[222] NorthAmerica[edit] ManystudiesinNorthAmericahaveexaminedecologicalandenvironmentalcorrelatesofthenumberofpeopleaffectedbyLymedisease.A2005studyusingclimatesuitabilitymodellingofI.scapularisprojectedthatclimatechangewouldcauseanoverall213%increaseinsuitablevectorhabitatbytheyear2080,withnorthwardexpansionsinCanada,increasedsuitabilityinthecentralU.S.,anddecreasedsuitablehabitatandvectorretractioninthesouthernU.S.[223]A2008reviewofpublishedstudiesconcludedthatthepresenceofforestsorforestedareaswastheonlyvariablethatconsistentlyelevatedtheriskofLymediseasewhereasotherenvironmentalvariablesshowedlittleornoconcordancebetweenstudies.[224]Theauthorsarguedthatthefactorsinfluencingtickdensityandhumanriskbetweensitesarestillpoorlyunderstood,andthatfuturestudiesshouldbeconductedoverlongertimeperiods,becomemorestandardizedacrossregions,andincorporateexistingknowledgeofregionalLymediseaseecology.[224] Canada[edit] Owingtochangingclimate,therangeofticksabletocarryLymediseasehasexpandedfromalimitedareaofOntariotoincludeareasofsouthernQuebec,Manitoba,northernOntario,southernNewBrunswick,southwestNovaScotiaandlimitedpartsofSaskatchewanandAlberta,aswellasBritishColumbia.CaseshavebeenreportedasfareastastheislandofNewfoundland.[110][225][226][227]Amodel-basedpredictionbyLeightonetal.(2012)suggeststhattherangeoftheI.scapularistickwillexpandintoCanadaby46 km/yearoverthenextdecade,withwarmingclimatictemperaturesasthemaindriverofincreasedspeedofspread.[228] Mexico[edit] A2007studysuggestsBorreliaburgdorferiinfectionsareendemictoMexico,fromfourcasesreportedbetween1999and2000.[229] UnitedStates[edit] CDCmapshowingtheriskofLymediseaseintheUnitedStates,particularlyitsconcentrationintheNortheastMegalopolisandwesternWisconsin. Eachyear,approximately30,000newcasesarereportedtotheCDC;however,thisnumberislikelyunderestimated.TheCDCiscurrentlyconductingresearchonevaluationanddiagnosticsofthediseaseandpreliminaryresultssuggestthenumberofnewcasestobearound300,000.[230][231] Lymediseaseisthemostcommontick-bornediseaseinNorthAmericaandEurope,andoneofthefastest-growinginfectiousdiseasesintheUnitedStates.OfcasesreportedtotheUnitedStatesCDC,theratioofLymediseaseinfectionis7.9casesforevery100,000persons.InthetenstateswhereLymediseaseismostcommon,theaveragewas31.6casesforevery100,000personsfortheyear2005.[232][233][234] AlthoughLymediseasehasbeenreportedinallstates[230][235]about99%ofallreportedcasesareconfinedtojustfivegeographicareas(NewEngland,Mid-Atlantic,East-NorthCentral,SouthAtlantic,andWestNorth-Central).[236]New2011CDCLymecasedefinitionguidelinesareusedtodetermineconfirmedCDCsurveillancecases.[237] EffectiveJanuary2008,theCDCgivesequalweighttolaboratoryevidencefrom1apositivecultureforB.burgdorferi;2)two-tiertesting(ELISAscreeningandWesternblotconfirming);or3)single-tierIgG(oldinfection)Westernblot.[238]Previously,theCDConlyincludedlaboratoryevidencebasedon(1)and(2)intheirsurveillancecasedefinition.ThecasedefinitionnowincludestheuseofWesternblotwithoutpriorELISAscreen.[238] Thenumberofreportedcasesofthediseasehasbeenincreasing,asareendemicregionsinNorthAmerica.Forexample,B.burgdorferisensulatowaspreviouslythoughttobehinderedinitsabilitytobemaintainedinanenzooticcycleinCalifornia,becauseitwasassumedthelargelizardpopulationwoulddilutethenumberofpeopleaffectedbyB.burgdorferiinlocaltickpopulations;thishassincebeenbroughtintoquestion,assomeevidencehassuggestedlizardscanbecomeinfected.[239] ExceptforonestudyinEurope,[240]muchofthedataimplicatinglizardsisbasedonDNAdetectionofthespirocheteandhasnotdemonstratedthatlizardsareabletoinfectticksfeedinguponthem.[239][241][242][243]AssomeexperimentssuggestlizardsarerefractorytoinfectionwithBorrelia,itappearslikelytheirinvolvementintheenzooticcycleismorecomplexandspecies-specific.[78] WhileB.burgdorferiismostassociatedwithtickshostedbywhite-taileddeerandwhite-footedmice,Borreliaafzeliiismostfrequentlydetectedinrodent-feedingvectorticks,andBorreliagariniiandBorreliavalaisianaappeartobeassociatedwithbirds.BothrodentsandbirdsarecompetentreservoirhostsforB.burgdorferisensustricto.TheresistanceofagenospeciesofLymediseasespirochetestothebacteriolyticactivitiesofthealternativecomplementpathwayofvarioushostspeciesmaydetermineitsreservoirhostassociation.[citationneeded] Severalsimilarbutapparentlydistinctconditionsmayexist,causedbyvariousspeciesorsubspeciesofBorreliainNorthAmerica.AregionallyrestrictedconditionthatmayberelatedtoBorreliainfectionissoutherntick-associatedrashillness(STARI),alsoknownasMastersdisease.Amblyommaamericanum,knowncommonlyasthelone-startick,isrecognizedastheprimaryvectorforSTARI.InsomepartsofthegeographicaldistributionofSTARI,Lymediseaseisquiterare(e.g.,Arkansas),sopeopleintheseregionsexperiencingLyme-likesymptoms—especiallyiftheyfollowabitefromalone-startick—shouldconsiderSTARIasapossibility.ItisgenerallyamilderconditionthanLymeandtypicallyrespondswelltoantibiotictreatment.[244] Inrecentyearstherehavebeen5to10casesayearofadiseasesimilartoLymeoccurringinMontana.ItoccursprimarilyinpocketsalongtheYellowstoneRiverincentralMontana.Peoplehavedevelopedaredbull's-eyerasharoundatickbitefollowedbyweeksoffatigueandafever.[235] Lymediseaseeffectsarecomparableamongmalesandfemales.Awiderangeofagegroupsisaffected,thoughthenumberofcasesishighestamong10-to19-year-olds.Forunknownreasons,LymediseaseisseventimesmorecommonamongAsians.[245] SouthAmerica[edit] InSouthAmerica,tick-bornediseaserecognitionandoccurrenceisrising.InBrazil,aLyme-likediseaseknownasBaggio–Yoshinarisyndromewasidentified,causedbymicroorganismsthatdonotbelongtotheB.burgdorferisensulatocomplexandtransmittedbyticksoftheAmblyommaandRhipicephalusgenera.[246]ThefirstreportedcaseofBYSinBrazilwasmadein1992inCotia,SãoPaulo.[247] History[edit] TheevolutionaryhistoryofBorreliaburgdorferigeneticshasbeenthesubjectofrecentstudies.Onestudyhasfoundthatpriortothereforestationthataccompaniedpost-colonialfarmabandonmentinNewEnglandandthewholesalemigrationintothemid-westthatoccurredduringtheearly19thcentury,LymediseasewaspresentforthousandsofyearsinAmericaandhadspreadalongwithitstickhostsfromtheNortheasttotheMidwest.[248] JohnJosselyn,whovisitedNewEnglandin1638andagainfrom1663to1670,wrote"therebeinfinitenumbersoftickshanginguponthebushesinsummertimethatwillcleavetoman'sgarmentsandcreepintohisbreeches,eatingthemselvesinashorttimeintotheveryfleshofaman.Ihaveseenthestockingsofthosethathavegonethroughthewoodscoveredwiththem."[249] ThisisalsoconfirmedbythewritingsofPeterKalm,aSwedishbotanistwhowassenttoAmericabyLinnaeus,andwhofoundtheforestsofNewYork"abound"withtickswhenhevisitedin1749.WhenKalm'sjourneywasretraced100yearslater,theforestsweregoneandtheLymebacteriumhadprobablybecomeisolatedtoafewpocketsalongthenortheastcoast,Wisconsin,andMinnesota.[250] PerhapsthefirstdetaileddescriptionofwhatisnowknownasLymediseaseappearedinthewritingsofJohnWalkerafteravisittotheislandofJura(DeerIsland)offthewestcoastofScotlandin1764.[251]HegivesagooddescriptionbothofthesymptomsofLymedisease(with"exquisitepain[in]theinteriorpartsofthelimbs")andofthetickvectoritself,whichhedescribesasa"worm"withabodywhichis"ofareddishcolorandofacompressedshapewitharowoffeetoneachside"that"penetratestheskin".ManypeoplefromthisareaofGreatBritainemigratedtoNorthAmericabetween1717andtheendofthe18thcentury.[citationneeded] TheexaminationofpreservedmuseumspecimenshasfoundBorreliaDNAinaninfectedIxodesricinustickfromGermanythatdatesbackto1884,andfromaninfectedmousefromCapeCodthatdiedin1894.[250]The2010autopsyofÖtzitheIceman,a5,300-year-oldmummy,revealedthepresenceoftheDNAsequenceofBorreliaburgdorferimakinghimtheearliestknownhumanwithLymedisease.[252] TheearlyEuropeanstudiesofwhatisnowknownasLymediseasedescribeditsskinmanifestations.Thefirststudydatesto1883inBreslau,Germany(nowWrocław,Poland),wherephysicianAlfredBuchwalddescribedamanwhohadsufferedfor16yearswithadegenerativeskindisordernowknownasacrodermatitischronicaatrophicans.[253] Ata1909researchconference,SwedishdermatologistArvidAfzeliuspresentedastudyaboutanexpanding,ring-likelesionhehadobservedinanolderwomanfollowingthebiteofasheeptick.Henamedthelesionerythemamigrans.[253]Theskinconditionnowknownasborreliallymphocytomawasfirstdescribedin1911.[254] Themodernhistoryofmedicalunderstandingofthedisease,includingitscause,diagnosis,andtreatment,hasbeendifficult.[255] Neurologicalproblemsfollowingtickbiteswererecognizedstartinginthe1920s.FrenchphysiciansGarinandBujadouxdescribedafarmerwithapainfulsensoryradiculitisaccompaniedbymildmeningitisfollowingatickbite.Alarge,ring-shapedrashwasalsonoted,althoughthedoctorsdidnotrelateittothemeningoradiculitis.In1930,theSwedishdermatologistSvenHellerströmwasthefirsttoproposeEMandneurologicalsymptomsfollowingatickbitewererelated.[256]Inthe1940s,GermanneurologistAlfredBannwarthdescribedseveralcasesofchroniclymphocyticmeningitisandpolyradiculoneuritis,someofwhichwereaccompaniedbyerythematousskinlesions. CarlLennhoff,whoworkedattheKarolinskaInstituteinSweden,believedmanyskinconditionswerecausedbyspirochetes.In1948,heusedaspecialstaintomicroscopicallyobservewhathebelievedwerespirochetesinvarioustypesofskinlesions,includingEM.[257]Althoughhisconclusionswerelatershowntobeerroneous,interestinthestudyofspirocheteswassparked.In1949,NilsThyresson,whoalsoworkedattheKarolinskaInstitute,wasthefirsttotreatACAwithpenicillin.[258]Inthe1950s,therelationshipamongtickbite,lymphocytoma,EMandBannwarth'ssyndromewasrecognizedthroughoutEuropeleadingtothewidespreaduseofpenicillinfortreatmentinEurope.[259][260] In1970,adermatologistinWisconsinnamedRudolphScrimentirecognizedanEMlesioninapersonafterrecallingapaperbyHellerströmthathadbeenreprintedinanAmericansciencejournalin1950.ThiswasthefirstdocumentedcaseofEMintheUnitedStates.BasedontheEuropeanliterature,hetreatedthepersonwithpenicillin.[261] ThefullsyndromenowknownasLymediseasewasnotrecognizeduntilaclusterofcasesoriginallythoughttobejuvenilerheumatoidarthritiswasidentifiedinthreetownsinsoutheasternConnecticutin1975,includingthetownsLymeandOldLyme,whichgavethediseaseitspopularname.[262]ThiswasinvestigatedbyphysiciansDavidSnydmanandAllenSteereoftheEpidemicIntelligenceService,andbyothersfromYaleUniversity,includingStephenMalawista,whoiscreditedasaco-discoverofthedisease.[263]TherecognitionthatthepeopleintheUnitedStateshadEMledtotherecognitionthat"Lymearthritis"wasonemanifestationofthesametick-borneconditionknowninEurope.[264] Before1976,theelementsofB.burgdorferisensulatoinfectionwerecalledorknownastick-bornemeningopolyneuritis,Garin-Bujadouxsyndrome,Bannwarthsyndrome,Afzelius'sdisease,[265]MontaukKneeorsheeptickfever.Since1976thediseaseismostoftenreferredtoasLymedisease,[266][267]Lymeborreliosisorsimplyborreliosis.[268][269] In1980,Steere,etal.,begantotestantibioticregimensinadultswithLymedisease.[270]Inthesameyear,NewYorkStateHealthDept.epidemiologistJorgeBenachprovidedWillyBurgdorfer,aresearcherattheRockyMountainBiologicalLaboratory,withcollectionsofI.dammini[scapularis]fromShelterIsland,NewYork,aknownLyme-endemicareaaspartofanongoinginvestigationofRockyMountainspottedfever.Inexaminingtheticksforrickettsiae,Burgdorfernoticed"poorlystained,ratherlong,irregularlycoiledspirochetes."Furtherexaminationrevealedspirochetesin60%oftheticks.BurgdorfercreditedhisfamiliaritywiththeEuropeanliteratureforhisrealizationthatthespirochetesmightbethe"long-soughtcauseofECMandLymedisease."BenachsuppliedhimwithmoreticksfromShelterIslandandserafrompeoplediagnosedwithLymedisease.UniversityofTexasHealthScienceCenterresearcherAlanBarbour"offeredhisexpertisetocultureandimmunochemicallycharacterizetheorganism."Burgdorfersubsequentlyconfirmedhisdiscoverybyisolating,frompeoplewithLymedisease,spirochetesidenticaltothosefoundinticks.[271]InJune1982,hepublishedhisfindingsinScience,andthespirochetewasnamedBorreliaburgdorferiinhishonor.[272] AftertheidentificationofB.burgdorferiasthecausativeagentofLymedisease,antibioticswereselectedfortesting,guidedbyinvitroantibioticsensitivities,includingtetracyclineantibiotics,amoxicillin,cefuroximeaxetil,intravenousandintramuscularpenicillinandintravenousceftriaxone.[273][274]Themechanismofticktransmissionwasalsothesubjectofmuchdiscussion.B.burgdorferispirocheteswereidentifiedinticksalivain1987,confirmingthehypothesisthattransmissionoccurredviaticksalivaryglands.[275] Societyandculture[edit] UrbanizationandotheranthropogenicfactorscanbeimplicatedinthespreadofLymediseasetohumans.Inmanyareas,expansionofsuburbanneighborhoodshasledtogradualdeforestationofsurroundingwoodedareasandincreasedbordercontactbetweenhumansandtick-denseareas.Humanexpansionhasalsoresultedinareductionofpredatorsthathuntdeeraswellasmice,chipmunksandothersmallrodents—theprimaryreservoirsforLymedisease.Asaconsequenceofincreasedhumancontactwithhostandvector,thelikelihoodoftransmissionofthediseasehasgreatlyincreased.[276][277]Researchersareinvestigatingpossiblelinksbetweenglobalwarmingandthespreadofvector-bornediseases,includingLymedisease.[278] Controversy[edit] Mainarticle:ChronicLymedisease Theterm"chronicLymedisease"iscontroversialandnotrecognizedinthemedicalliterature,[279]andmostmedicalauthoritiesadviseagainstlong-termantibiotictreatmentforLymedisease.[36][118][280]Studieshaveshownthatmostpeoplediagnosedwith"chronicLymedisease"eitherhavenoobjectiveevidenceofpreviousorcurrentinfectionwithB.burgdorferiorarepeoplewhoshouldbeclassifiedashavingpost-treatmentLymediseasesyndrome(PTLDS),whichisdefinedascontinuingorrelapsingnon-specificsymptoms(suchasfatigue,musculoskeletalpain,andcognitivecomplaints)inapersonpreviouslytreatedforLymedisease.[281] The2008documentaryUnderOurSkinisknownforpromotingconspiracytheoriesabout"chronicLymedisease".[282] Otheranimals[edit] Pets[edit] PreventionofLymediseaseisanimportantstepinkeepingdogssafeinendemicareas.Preventioneducationandanumberofpreventivemeasuresareavailable.First,fordogownerswholivenearorwhooftenfrequenttick-infestedareas,routinevaccinationsoftheirdogsisanimportantstep.[283] Anothercrucialpreventivemeasureistheuseofpersistentacaricides,suchastopicalrepellentsorpesticidesthatcontaintriazapentadienes(Amitraz),phenylpyrazoles(Fipronil),orpermethrin(pyrethroids).[284]TheseacaricidestargetprimarilytheadultstagesofLyme-carryingticksandreducethenumberofreproductivelyactiveticksintheenvironment.[283]Formulationsoftheseingredientsareavailableinavarietyoftopicalforms,includingspot-ons,sprays,powders,impregnatedcollars,solutions,andshampoos.[284] Examinationofadogforticksafterbeinginatick-infestedareaisanimportantprecautionarymeasuretotakeinthepreventionofLymedisease.Keyspotstoexamineincludethehead,neck,andears.[285] Indogs,aseriouslong-termprognosismayresultinglomerulardisease,[286]whichisacategoryofkidneydamagethatmaycausechronickidneydisease.[171]Dogsmayalsoexperiencechronicjointdiseaseifthediseaseisleftuntreated.However,themajorityofcasesofLymediseaseindogsresultincompleterecoverywith,andsometimeswithout,treatmentwithantibiotics.[287][verificationneeded]Inrarecases,Lymediseasecanbefataltobothhumansanddogs.[288] References[edit] ^abcdefghijk"SignsandSymptomsofLymeDisease".cdc.gov.11January2013.Archivedfromtheoriginalon16January2013.Retrieved2March2015. ^abcdefghijklmnopqrstuvwxyzaaabacadaeafagShapiroED(May2014)."Clinicalpractice.Lymedisease"(PDF).TheNewEnglandJournalofMedicine.370(18):1724–1731.doi:10.1056/NEJMcp1314325.PMC 4487875.PMID 24785207.Archivedfromtheoriginal(PDF)on21August2016.Retrieved5July2016. ^ab"LymeDiseaseDiagnosisandTesting".cdc.gov.10January2013.Archivedfromtheoriginalon2March2015.Retrieved2March2015. ^"ConcernaboutLymedisease|CDC".13January2021. ^Kugeler,KierstenJ.;Schwartz,AmyM.;Delorey,MarkJ.;Mead,PaulS.;Hinckley,AlisonF.(2021)."EstimatingtheFrequencyofLymeDiseaseDiagnoses,UnitedStates,2010–2018".EmergingInfectiousDiseases.27(2):616–619.doi:10.3201/eid2702.202731.PMC 7853543.PMID 33496229. ^abcWenner,Melinda(11June2021)."Let'sDoaTickCheck-ThesepervasivebloodsuckerscangiveyoumorethanjustLymedisease.Here'showtoprotectyourself.(Interactive)".TheNewYorkTimes.Retrieved19June2021. ^abcWolcott,KatherineA.;Margos,Gabriele;Fingerle,Volker;Becker,NoémieS.(1September2021)."HostassociationofBorreliaburgdorferisensulato:Areview".TicksandTick-borneDiseases.12(5):101766.doi:10.1016/j.ttbdis.2021.101766.ISSN 1877-959X.PMID 34161868. ^Aucott,J.;Morrison,C.;Munoz,B.;Rowe,P.C.;Schwarzwalder,A.;West,S.K.(2009)."DiagnosticchallengesofearlyLymedisease:Lessonsfromacommunitycaseseries".BMCInfectiousDiseases.NationalLibraryofMedicine.9:79.doi:10.1186/1471-2334-9-79.PMC 2698836.PMID 19486523. ^AucottJN(June2015)."PosttreatmentLymediseasesyndrome".InfectiousDiseaseClinicsofNorthAmerica.29(2):309–323.doi:10.1016/j.idc.2015.02.012.PMID 25999226. ^JohnsonRC(1996)."Borrelia".InBaronS,et al.(eds.).Baron'sMedicalMicrobiology(4th ed.).UnivofTexasMedicalBranch.ISBN 978-0-9631172-1-2.PMID 21413339.Archivedfromtheoriginalon7February2009. ^ab"Lymediseasetransmission".cdc.gov.11January2013.Archivedfromtheoriginalon3March2015.Retrieved2March2015. ^abSteere,AC;Strle,F;Wormser,GP;Hu,LT;Branda,JA;Hovius,JW;Li,X;Mead,PS(15December2016)."Lymeborreliosis".NatureReviews.DiseasePrimers.2:16090.doi:10.1038/nrdp.2016.90.PMC 5539539.PMID 27976670. ^"Lymeborreliosis"(PDF).ECDC.Archived(PDF)fromtheoriginalon29September2018.Retrieved29September2018. ^abPrittBS,MeadPS,JohnsonDK,NeitzelDF,Respicio-KingryLB,DavisJP,SchiffmanE,SloanLM,SchrieferME,ReplogleAJ,PaskewitzSM,RayJA,BjorkJ,StewardCR,DeedonA,LeeX,KingryLC,MillerTK,FeistMA,TheelES,PatelR,IrishCL,PetersenJM(May2016)."IdentificationofanovelpathogenicBorreliaspeciescausingLymeborreliosiswithunusuallyhighspirochaetaemia:adescriptivestudy".TheLancet.InfectiousDiseases.16(5):556–564.doi:10.1016/S1473-3099(15)00464-8.PMC 4975683.PMID 26856777. ^"Two-stepLaboratoryTestingProcess".cdc.gov.15November2011.Archivedfromtheoriginalon12March2015.Retrieved2March2015. ^"TestingofTicks".cdc.gov.4June2013.Archivedfromtheoriginalon19February2015.Retrieved2March2015.Althoughsomecommercialgroupsoffertesting,ingeneralthisisnotrecommended ^"TickRemoval".cdc.gov.23June2014.Archivedfromtheoriginalon10March2015.Retrieved2March2015. ^abc"Post-TreatmentLymeDiseaseSyndrome".cdc.gov.1December2017.Archivedfromtheoriginalon27February2015.Retrieved20June2018. ^RegionalDiseaseVectorEcologyProfile:CentralEurope.DIANEPublishing.April2001.p. 136.ISBN 9781428911437.Archivedfromtheoriginalon8September2017. ^Berger,Stephen(2014).Lymedisease:GlobalStatus2014Edition.GIDEONInformaticsInc.p. 7.ISBN 9781498803434.Archivedfromtheoriginalon8September2017. ^Murray,Polly(1006).TheWideningCircle :ALymeDiseasePioneerTellsHerStory.NewYork:St.Martin'sPress.ISBN 9780312140687. ^Williams,Carolyn(2007).Infectiousdiseaseepidemiology :theoryandpractice(2nd ed.).Sudbury,Mass.:JonesandBartlettPublishers.p. 447.ISBN 9780763728793.Archivedfromtheoriginalon8September2017. ^"WillyBurgdorfer–obituary".DailyTelegraph.1December2014.Archivedfromtheoriginalon1December2014.Retrieved1December2014. ^Baker,PJ(November2010)."ChronicLymedisease:indefenseofthescientificenterprise".FASEBJournal.24(11):4175–7.doi:10.1096/fj.10-167247.PMID 20631327.S2CID 36141950. ^LantosPM(June2015)."ChronicLymedisease".InfectiousDiseaseClinicsofNorthAmerica.29(2):325–40.doi:10.1016/j.idc.2015.02.006.PMC 4477530.PMID 25999227. ^ab"Whenavaccineissafe".Nature.439(7076):509.February2006.Bibcode:2006Natur.439Q.509..doi:10.1038/439509a.PMID 16452935. ^Aronowitz,RobertA(June2016)."TheRiseandFalloftheLymeDiseaseVaccines:ACautionaryTaleforRiskInterventionsinAmericanMedicineandPublicHealth".TheMilbankQuarterly.90(2):250–277.doi:10.1111/j.1468-0009.2012.00663.x.ISSN 0887-378X.PMC 3460208.PMID 22709388. ^abcdefghijklmnopqrstuvwxyzaaabacWrightWF,RiedelDJ,TalwaniR,GilliamBL(June2012)."DiagnosisandmanagementofLymedisease".AmericanFamilyPhysician.85(11):1086–93.PMID 22962880.Archivedfromtheoriginalon27September2013. ^abcdTibblesCD,EdlowJA(20June2007)."DoesThisPatientHaveErithemaMigrans?".JAMA.297(23):2617–27.doi:10.1001/jama.297.23.2617.PMID 17579230. ^abc"Lymediseaserashesandlook-alikes".LymeDisease.CentersforDiseaseControlandPrevention.21December2018.Archivedfromtheoriginalon2April2019.Retrieved18April2019. ^abc"Lymedisease:erythemamigrans".LymediseaseNICEguideline[NG95].NationalInstituteforHealthandCareExcellence.Archivedfromtheoriginalon9May2019.Retrieved8May2019. ^"LymeDisease".TheLecturioMedicalConceptLibrary.Retrieved9July2021. ^abLymediseaseateMedicine ^SteereAC,SikandVK,SchoenRT,NowakowskiJ(August2003)."AsymptomaticinfectionwithBorreliaburgdorferi".ClinicalInfectiousDiseases.37(4):528–32.doi:10.1086/376914.PMID 12905137.(primarysource) ^abBiesiadaG,CzepielJ,LeśniakMR,GarlickiA,MachT(December2012)."Lymedisease:review".ArchivesofMedicalScience.8(6):978–82.doi:10.5114/aoms.2012.30948.PMC 3542482.PMID 23319969. ^abcdefghijklmnopqrstuvwxyzaaabacadaeafagahWormserGP,DattwylerRJ,ShapiroED,HalperinJJ,SteereAC,KlempnerMS,KrausePJ,BakkenJS,StrleF,StanekG,BockenstedtL,FishD,DumlerJS,NadelmanRB(November2006)."Theclinicalassessment,treatment,andpreventionoflymedisease,humangranulocyticanaplasmosis,andbabesiosis:clinicalpracticeguidelinesbytheInfectiousDiseasesSocietyofAmerica".ClinicalInfectiousDiseases.43(9):1089–134.doi:10.1086/508667.PMID 17029130. ^abHalperinJJ(June2008)."NervoussystemLymedisease".InfectiousDiseaseClinicsofNorthAmerica.22(2):261–74,vi.doi:10.1016/j.idc.2007.12.009.PMID 18452800. ^abcdefghijMyglandA,LjøstadU,FingerleV,RupprechtT,SchmutzhardE,SteinerI(January2010)."EFNSguidelinesonthediagnosisandmanagementofEuropeanLymeneuroborreliosis"(PDF).EuropeanJournalofNeurology.17(1):8–16.doi:10.1111/j.1468-1331.2009.02862.x.PMID 19930447.S2CID 14166137.Archived(PDF)fromtheoriginalon8August2017.Retrieved30April2019. ^abcdePachnerAR,SteereAC(July1984)."NeurologicalfindingsofLymedisease".YaleJournalofBiologyandMedicine.57(4):481–3.PMC 2590042.PMID 6516450. ^Moscatello,AugustineL.;Worden,DouglasL.;Nadelman,RobertB.;Wormser,Gary;Lucente,Frank(June1991)."OtolaryngologicAspectsofLymeDisease".TheLaryngoscope.101(6):592–595.doi:10.1288/00005537-199106000-00004.PMID 2041438.S2CID 35345898. ^abcdefghOgrincK,LusaL,Lotrič-FurlanS,BogovičP,StupicaD,CerarT,Ružić-SabljićE,StrleF(August2016)."CourseandoutcomeofearlyEuropeanLymeneuroborreliosis(Bannwarthsyndrome):clinicalandlaboratoryfindings".ClinicalInfectiousDiseases.63(3):346–53.doi:10.1093/cid/ciw299.PMID 27161773. ^abcdefghiGarroA,NigrovicLE(May2018)."ManagingPeripheralFacialPalsy".AnnalsofEmergencyMedicine.71(5):618–623.doi:10.1016/j.annemergmed.2017.08.039.PMID 29110887. ^abHalperinJJ(September2010)."NervoussystemLymedisease".JRCollPhysiciansEdinb.40(3):248–55.doi:10.4997/JRCPE.2010.314.PMID 21127770. ^abcdefghijklmnoFishAE,PrideYB,PintoDS(June2008)."Lymecarditis"(PDF).InfectDisClinNorthAm.22(2):275–88.doi:10.1016/j.idc.2007.12.008.PMID 18452801.Archived(PDF)fromtheoriginalon29August2017.Retrieved9May2019. ^abStanekG,WormserGP,GrayJ,StrleF(February2012)."Lymeborreliosis".Lancet.379(9814):461–73.doi:10.1016/S0140-6736(11)60103-7.PMID 21903253.S2CID 31461047. ^abStanekG,StrleF(June2008)."Lymedisease:Europeanperspective".InfectiousDiseaseClinicsofNorthAmerica.22(2):327–39,vii.doi:10.1016/j.idc.2008.01.001.PMID 18452805. ^PuiusYA,KalishRA(June2008)."Lymearthritis:pathogenesis,clinicalpresentation,andmanagement".InfectiousDiseaseClinicsofNorthAmerica.22(2):289–300,vi–vii.doi:10.1016/j.idc.2007.12.014.PMID 18452802. ^abAuwaerterPG,AucottJ,DumlerJS(January2004)."Lymeborreliosis(Lymedisease):molecularandcellularpathobiologyandprospectsforprevention,diagnosisandtreatment".ExpertReviewsinMolecularMedicine.6(2):1–22.doi:10.1017/S1462399404007276.PMID 14987414. ^BrattonRL,WhitesideJW,HovanMJ,EngleRL,EdwardsFD(May2008)."DiagnosisandtreatmentofLymedisease".MayoClinicProceedings.83(5):566–571.doi:10.4065/83.5.566.PMID 18452688. ^ShadickNA,PhillipsCB,SanghaO,LogigianEL,KaplanRF,WrightEA,FosselAH,FosselK,BerardiV,LewRA,LiangMH(December1999)."MusculoskeletalandneurologicoutcomesinpatientswithpreviouslytreatedLymedisease".AnnalsofInternalMedicine.131(12):919–26.doi:10.7326/0003-4819-131-12-199912210-00003.PMID 10610642.S2CID 20746489. ^SeltzerEG,GerberMA,CartterML,FreudigmanK,ShapiroED(February2000)."Long-termoutcomesofpersonswithLymedisease".JAMA.283(5):609–16.doi:10.1001/jama.283.5.609.PMID 10665700. ^FallonBA,NieldsJA(November1994)."Lymedisease:aneuropsychiatricillness".TheAmericanJournalofPsychiatry.151(11):1571–83.doi:10.1176/ajp.151.11.1571.PMID 7943444.S2CID 22568915. ^HessA,BuchmannJ,ZettlUK,HenschelS,SchlaefkeD,GrauG,BeneckeR(March1999)."Borreliaburgdorfericentralnervoussysteminfectionpresentingasanorganicschizophrenialikedisorder".BiologicalPsychiatry.45(6):795.doi:10.1016/S0006-3223(98)00277-7.PMID 10188012.S2CID 44486654. ^MulleggerRR(2004)."DermatologicalmanifestationsofLymeborreliosis".EuropeanJournalofDermatology.14(5):296–309.PMID 15358567. ^SamuelsDS,RadolfJD,eds.(2010)."Chapter6,Structure,FunctionandBiogenesisoftheBorreliaCellEnvelope".Borrelia:MolecularBiology,HostInteractionandPathogenesis.CaisterAcademicPress.ISBN 978-1-904455-58-5. ^RadolfJD,SamuelsDS,eds.(2021).LymeDiseaseandRelapsingFeverSpirochetes:Genomics,MolecularBiology,HostInteractions,andDiseasePathogenesis.CaisterAcademicPress.ISBN 978-1-913652-61-6. ^CutlerSJ,Ruzic-SabljicE,PotkonjakA(February2017).borreliosisforsubmissionmodHPFAug10_correctedwithouttrackchangeSJC.pdf"Emergingborreliae–ExpandingbeyondLymeborreliosis"Check|url=value(help)(PDF).MolecularandCellularProbes.31:22–27.doi:10.1016/j.mcp.2016.08.003.PMID 27523487.borreliosisforsubmissionmodHPFAug10_correctedwithouttrackchangeSJC.pdfArchivedCheck|archive-url=value(help)(PDF)fromtheoriginalon20July2018.Retrieved5July2019. ^StanekG,ReiterM(April2011)."TheexpandingLymeBorreliacomplex--clinicalsignificanceofgenomicspecies?".ClinicalMicrobiologyandInfection.17(4):487–93.doi:10.1111/j.1469-0691.2011.03492.x.PMID 21414082. ^SchneiderBS,SchrieferME,DietrichG,DolanMC,MorshedMG,ZeidnerNS(October2008)."Borreliabissettiiisolatesinducepathologyinamurinemodelofdisease".VectorBorneandZoonoticDiseases.8(5):623–33.doi:10.1089/vbz.2007.0251.PMID 18454594.Archivedfromtheoriginalon29January2020.Retrieved29January2020. ^RudenkoN,GolovchenkoM,MokrácekA,PiskunováN,RuzekD,MallatováN,GrubhofferL(October2008)."DetectionofBorreliabissettiiincardiacvalvetissueofapatientwithendocarditisandaorticvalvestenosisintheCzechRepublic".JournalofClinicalMicrobiology.46(10):3540–3.doi:10.1128/JCM.01032-08.PMC 2566110.PMID 18650352. ^"UpToDate".www.uptodate.com.Retrieved10July2021. ^abTillyK,RosaPA,StewartPE(June2008)."BiologyofinfectionwithBorreliaburgdorferi".InfectiousDiseaseClinicsofNorthAmerica.22(2):217–34,v.doi:10.1016/j.idc.2007.12.013.PMC 2440571.PMID 18452798. ^abcdRyanKJ,RayCG,eds.(2004).SherrisMedicalMicrobiology(4th ed.).McGrawHill.pp. 434–37.ISBN 978-0-8385-8529-0. ^2005FactSheet,PreventTickBites:PreventLymeDiseaseArchived26June2013attheWaybackMachine,RutgersUniversity,RutgersCooperativeResearch&Extension,NewJerseyAgriculturalExperimentStation,DeborahSmith-Fiola,FormerOceanCountyAgriculturalAgentandGeorgeC.Hamilton,PhD,ExtensionSpecialistinPestManagement,March2005. ^PeoplearefreakingoutovertheCDC'sphotoofamuffinwithticksinitArchived25January2020attheWaybackMachine,DeseretNews(Utah),HerbScribner,31May2019.TheU.S.CDCpublishedapictureofapoppyseedmuffininwhichsomeofthe"poppyseeds"wereactuallyticks. ^abLoReV,OcciJL,MacGregorRR(April2004)."IdentifyingthevectorofLymedisease".AmericanFamilyPhysician.69(8):1935–7.PMID 15117014. ^"WestportWestonHealthDistrict".2004.Archivedfromtheoriginalon29September2013.Retrieved26September2013. ^ab"LymeDiseaseDataandsurveillance".LymeDisease.CentersforDiseaseControlandPrevention.5February2019.Archivedfromtheoriginalon13April2019.Retrieved12April2019. ^HoviusJW,vanDamAP,FikrigE(September2007)."Tick-host-pathogeninteractionsinLymeborreliosis"(PDF).TrendsinParasitology.23(9):434–8.doi:10.1016/j.pt.2007.07.001.PMID 17656156.Archived(PDF)fromtheoriginalon16February2019.Retrieved9September2019. ^abcSteereAC,CoburnJ,GlicksteinL(April2004)."TheemergenceofLymedisease".TheJournalofClinicalInvestigation.113(8):1093–101.doi:10.1172/JCI21681.PMC 385417.PMID 15085185. ^Hu,Linden(13May2019)."Patienteducation:WhattodoafteratickbitetopreventLymedisease(BeyondtheBasics)".www.uptodate.com.UpToDate.Archivedfromtheoriginalon1January2020.Retrieved30January2020. ^deMikEL,vanPeltW,Docters-vanLeeuwenBD,vanderVeenA,SchellekensJF,BorgdorffMW(April1997)."ThegeographicaldistributionoftickbitesanderythemamigransingeneralpracticeinTheNetherlands".InternationalJournalofEpidemiology.26(2):451–7.doi:10.1093/ije/26.2.451.PMID 9169184. ^SunY,XuR(2003)."AbilityofIxodespersulcatus,HaemaphysalisconcinnaandDermacentorsilvarumtickstoacquireandtransstadiallytransmitBorreliagarinii".Experimental&AppliedAcarology.31(1–2):151–60.doi:10.1023/B:APPA.0000005119.30172.43.PMID 14756409.S2CID 19214181. ^LedinKE,ZeidnerNS,RibeiroJM,BiggerstaffBJ,DolanMC,DietrichG,VredevoeL,PiesmanJ(March2005)."BorreliacidalactivityofsalivaofthetickAmblyommaamericanum".MedicalandVeterinaryEntomology.19(1):90–5.doi:10.1111/j.0269-283X.2005.00546.x.PMID 15752182.S2CID 270178. ^MastersEJ,GrigeryCN,MastersRW(June2008)."STARI,orMastersdisease:LoneStartick-vectoredLyme-likeillness".InfectiousDiseaseClinicsofNorthAmerica.22(2):361–76,viii.doi:10.1016/j.idc.2007.12.010.PMID 18452807. ^ClarkK(November2004)."Borreliaspeciesinhost-seekingticksandsmallmammalsinnorthernFlorida".JournalofClinicalMicrobiology.42(11):5076–86.doi:10.1128/JCM.42.11.5076-5086.2004.PMC 525154.PMID 15528699. ^EisenL,EisenRJ,LaneRS(December2004)."Therolesofbirds,lizards,androdentsashostsforthewesternblack-leggedtickIxodespacificus".JournalofVectorEcology.29(2):295–308.PMID 15709249. ^abLaneRS,MunJ,EisenL,EisenRJ(August2006)."Refractorinessofthewesternfencelizard(Sceloporusoccidentalis)totheLymediseasegroupspirocheteBorreliabissettii".TheJournalofParasitology.92(4):691–6.doi:10.1645/GE-738R1.1.PMID 16995383.S2CID 24200639. ^WalshCA,MayerEW,BaxiLV(January2007)."Lymediseaseinpregnancy:casereportandreviewoftheliterature".Obstetrical&GynecologicalSurvey.62(1):41–50.doi:10.1097/01.ogx.0000251024.43400.9a.PMID 17176487.S2CID 31929160. ^Dotters-Katz,S;Kuller,J;Heine,P(September2013)."Arthropod-BorneBacterialDiseasesinPregnancy".Obstetrical&GynecologicalSurvey.68(9):41–50.doi:10.1097/OGX.0b013e3182a5ed46.PMID 25102120.S2CID 26801402. ^LakosA,SolymosiN(June2010)."MaternalLymeborreliosisandpregnancyoutcome".InternationalJournalofInfectiousDiseases.14(6):e494–8.doi:10.1016/j.ijid.2009.07.019.PMID 19926325. ^SteereA(31August1989)."MedicalProgress,LymeDisease".TheNewEnglandJournalofMedicine.321(9):586–596.doi:10.1056/NEJM198908313210906.PMID 2668764. ^"TickAttachmentandTickborneDiseases".www.maine.gov.Archivedfromtheoriginalon1October2018.Retrieved1October2018. ^"CDCLymediseaseFAQ".CentersforDiseaseControlandPrevention.8January2021.Retrieved10September2021. ^SwansonSJ,NeitzelD,ReedKD,BelongiaEA(October2006)."Coinfectionsacquiredfromixodesticks".ClinicalMicrobiologyReviews.19(4):708–27.doi:10.1128/CMR.00011-06.PMC 1592693.PMID 17041141. ^WormserGP(June2006)."Clinicalpractice.EarlyLymedisease".TheNewEnglandJournalofMedicine.354(26):2794–801.doi:10.1056/NEJMcp061181.PMID 16807416. ^LindgrenE,GustafsonR(July2001)."Tick-borneencephalitisinSwedenandclimatechange".Lancet.358(9275):16–8.doi:10.1016/S0140-6736(00)05250-8.PMID 11454371.S2CID 336323. ^VardeS,BeckleyJ,SchwartzI(1998)."Prevalenceoftick-bornepathogensinIxodesscapularisinaruralNewJerseyCounty".EmergingInfectiousDiseases.4(1):97–9.doi:10.3201/eid0401.980113.PMC 2627663.PMID 9452402. ^PachnerAR,SteinerI(June2007)."Lymeneuroborreliosis:infection,immunity,andinflammation".TheLancet.Neurology.6(6):544–52.doi:10.1016/S1474-4422(07)70128-X.PMID 17509489.S2CID 11600373. ^FikrigE,NarasimhanS(April2006)."Borreliaburgdorferi--travelingincognito?".MicrobesandInfection.8(5):1390–9.doi:10.1016/j.micinf.2005.12.022.PMID 16698304. ^XuQ,SeemanapalliSV,ReifKE,BrownCR,LiangFT(April2007)."IncreasingtherecruitmentofneutrophilstothesiteofinfectiondramaticallyattenuatesBorreliaburgdorferiinfectivity".JournalofImmunology.178(8):5109–15.doi:10.4049/jimmunol.178.8.5109.PMID 17404293. ^ColemanJL,GebbiaJA,PiesmanJ,DegenJL,BuggeTH,BenachJL(June1997)."PlasminogenisrequiredforefficientdisseminationofB.burgdorferiinticksandforenhancementofspirochetemiainmice".Cell.89(7):1111–9.doi:10.1016/S0092-8674(00)80298-6.PMID 9215633.S2CID 18750257. ^SteereAC(July2001)."Lymedisease".TheNewEnglandJournalofMedicine.345(2):115–25.doi:10.1056/NEJM200107123450207.PMID 11450660. ^RupprechtTA,KoedelU,FingerleV,PfisterHW(2008)."Thepathogenesisoflymeneuroborreliosis:frominfectiontoinflammation".MolecularMedicine.14(3–4):205–12.doi:10.2119/2007-00091.Rupprecht.PMC 2148032.PMID 18097481.Archivedfromtheoriginalon3April2015. ^CabelloFC,GodfreyHP,NewmanSA(August2007)."Hiddeninplainsight:Borreliaburgdorferiandtheextracellularmatrix".TrendsinMicrobiology.15(8):350–4.doi:10.1016/j.tim.2007.06.003.PMID 17600717.Archivedfromtheoriginalon7July2019.Retrieved5July2019. ^RameshG,AlvarezAL,RobertsED,DennisVA,LasaterBL,AlvarezX,PhilippMT(September2003)."PathogenesisofLymeneuroborreliosis:Borreliaburgdorferilipoproteinsinducebothproliferationandapoptosisinrhesusmonkeyastrocytes".EuropeanJournalofImmunology.33(9):2539–50.doi:10.1002/eji.200323872.PMID 12938230.S2CID 25448372. ^HalperinJJ,HeyesMP(January1992)."NeuroactivekynureninesinLymeborreliosis".Neurology.42(1):43–50.doi:10.1212/WNL.42.1.43.PMID 1531156.S2CID 37495839. ^FallonBA,KeilpJ,ProhovnikI,HeertumRV,MannJJ(2003)."Regionalcerebralbloodflowandcognitivedeficitsinchroniclymedisease".TheJournalofNeuropsychiatryandClinicalNeurosciences.15(3):326–32.doi:10.1176/appi.neuropsych.15.3.326.PMID 12928508. ^GasseT,MurrC,MeyersbachP,SchmutzhardE,WachterH,FuchsD(September1994)."NeopterinproductionandtryptophandegradationinacuteLymeneuroborreliosisversuslateLymeencephalopathy".EuropeanJournalofClinicalChemistryandClinicalBiochemistry(Submittedmanuscript).32(9):685–9.doi:10.1515/cclm.1994.32.9.685.PMID 7865624.S2CID 22214184. ^ZajkowskaJ,GrygorczukS,KondrusikM,PancewiczS,Hermanowska-SzpakowiczT(2006)."[NewaspectsofpathogenesisofLymeborreliosis]".PrzegladEpidemiologiczny(inPolish).60Suppl1(Suppl1):167–70.PMID 16909797. ^ErcoliniAM,MillerSD(January2009)."Theroleofinfectionsinautoimmunedisease".ClinicalandExperimentalImmunology.155(1):1–15.doi:10.1111/j.1365-2249.2008.03834.x.PMC 2665673.PMID 19076824. ^SinghSK,GirschickHJ(July2004)."Lymeborreliosis:frominfectiontoautoimmunity".ClinicalMicrobiologyandInfection.10(7):598–614.doi:10.1111/j.1469-0691.2004.00895.x.PMID 15214872. ^OldstoneMB(October1998)."Molecularmimicryandimmune-mediateddiseases".FASEBJournal.12(13):1255–65.doi:10.1096/fasebj.12.13.1255.PMC 7164021.PMID 9761770.S2CID 16089636. ^RavecheES,SchutzerSE,FernandesH,BatemanH,McCarthyBA,NickellSP,CunninghamMW(February2005)."EvidenceofBorreliaautoimmunity-inducedcomponentofLymecarditisandarthritis".JournalofClinicalMicrobiology.43(2):850–6.doi:10.1128/JCM.43.2.850-856.2005.PMC 548028.PMID 15695691. ^WeinsteinA,BritchkovM(July2002)."Lymearthritisandpost-Lymediseasesyndrome".CurrentOpinioninRheumatology.14(4):383–7.doi:10.1097/00002281-200207000-00008.PMID 12118171. ^BolzDD,WeisJJ(August2004)."MolecularmimicrytoBorreliaburgdorferi:pathwaytoautoimmunity?".Autoimmunity.37(5):387–92.doi:10.1080/08916930410001713098.PMID 15621562.S2CID 43045224. ^BrownSL,HansenSL,LangoneJJ(July1999)."RoleofserologyinthediagnosisofLymedisease".JAMA.282(1):62–6.doi:10.1001/jama.282.1.62.PMID 10404913. ^HofmannH(1996)."Lymeborreliosis—problemsofserologicaldiagnosis".Infection.24(6):470–2.doi:10.1007/BF01713052.PMID 9007597.S2CID 19701481. ^WormserGP,MastersE,NowakowskiJ,McKennaD,HolmgrenD,MaK,IhdeL,CavaliereLF,NadelmanRB(October2005)."ProspectiveclinicalevaluationofpatientsfromMissouriandNewYorkwitherythemamigrans-likeskinlesions".ClinicalInfectiousDiseases.41(7):958–65.doi:10.1086/432935.PMID 16142659. ^ab"LymeDiseaseriskareasmap".RiskofLymediseasetoCanadians.GovernmentofCanada.27January2015.Archivedfromtheoriginalon10May2019.Retrieved8May2019. ^abcdefAucottJ,MorrisonC,MunozB,RowePC,SchwarzwalderA,WestSK(1June2009)."DiagnosticchallengesofearlyLymedisease:Lessonsfromacommunitycaseseries".BMCInfectiousDiseases.9(79):79.doi:10.1186/1471-2334-9-79.PMC 2698836.PMID 19486523. ^"Lymediseasediagnosis".CentersforDiseaseControlandPrevention(CDC).7October2008.Archivedfromtheoriginalon28August2009.Retrieved6July2009. ^ab"Lymedisease".NICEguideline[NG95].NationalInstituteforHealthandCareExcellence.Archivedfromtheoriginalon11May2019.Retrieved24May2019. ^WilskeB(2005)."EpidemiologyanddiagnosisofLymeborreliosis".AnnalsofMedicine.37(8):568–79.doi:10.1080/07853890500431934.PMID 16338759.S2CID 30818459. ^abcDepietropaoloDL,Powers,JH,GillJM,FoyAJ(15July2005)."DiagnosisofLymedisease".AmericanFamilyPhysician.72(2):297–305.doi:10.1093/cid/cir464.PMID 16050454. ^"AreserologicaltestsofanyvalueinthediagnosisofLymedisease?".AmericanLymeDiseaseFoundation.Archivedfromtheoriginalon19December2019.Retrieved2December2019. ^CoylePK,SchutzerSE,DengZ,KruppLB,BelmanAL,BenachJL,LuftBJ(November1995)."DetectionofBorreliaburgdorferi-specificantigeninantibody-negativecerebrospinalfluidinneurologicLymedisease".Neurology.45(11):2010–5.doi:10.1212/WNL.45.11.2010.PMID 7501150.S2CID 23797801. ^abcdHalperinJJ,ShapiroED,LogigianE,BelmanAL,DotevallL,WormserGP,KruppL,GronsethG,BeverCT(July2007)."Practiceparameter:treatmentofnervoussystemLymedisease(anevidence-basedreview):reportoftheQualityStandardsSubcommitteeoftheAmericanAcademyofNeurology".Neurology.69(1):91–102.doi:10.1212/01.wnl.0000265517.66976.28.PMID 17522387. ^MolloyPJ,PersingDH,BerardiVP(August2001)."False-positiveresultsofPCRtestingforLymedisease".ClinicalInfectiousDiseases.33(3):412–3.doi:10.1086/321911.PMID 11438915. ^abAguero-RosenfeldME,WangG,SchwartzI,WormserGP(July2005)."Diagnosisoflymeborreliosis".ClinicalMicrobiologyReviews.18(3):484–509.doi:10.1128/CMR.18.3.484-509.2005.PMC 1195970.PMID 16020686. ^NoctonJJ,DresslerF,RutledgeBJ,RysPN,PersingDH,SteereAC(January1994)."DetectionofBorreliaburgdorferiDNAbypolymerasechainreactioninsynovialfluidfrompatientswithLymearthritis".TheNewEnglandJournalofMedicine.330(4):229–34.doi:10.1056/NEJM199401273300401.PMID 8272083. ^HydeFW,JohnsonRC,WhiteTJ,ShelburneCE(January1989)."DetectionofantigensinurineofmiceandhumansinfectedwithBorreliaburgdorferi,etiologicagentofLymedisease".JournalofClinicalMicrobiology.27(1):58–61.doi:10.1128/JCM.27.1.58-61.1989.PMC 267232.PMID 2913036. ^ShafagatiN,PatanarutA,LuchiniA,LundbergL,BaileyC,PetricoinE,LiottaL,NarayananA,LepeneB,Kehn-HallK(July2014)."TheuseofNanotrapparticlesforbiodefenseandemerginginfectiousdiseasediagnostics".PathogensandDisease.71(2):164–76.doi:10.1111/2049-632X.12136.PMC 7108521.PMID 24449537. ^ShafagatiN,PatanarutA,LuchiniA,LundbergL,BaileyC,PetricoinE,LiottaL,NarayananA,LepeneB,Kehn-HallK(July2014)."TheuseofNanotrapparticlesforbiodefenseandemerginginfectiousdiseasediagnostics".PathogensandDisease.71(2):164–76.doi:10.1111/2049-632x.12136.PMC 7108521.PMID 24449537. ^BurdashN,FernandesJ(June1991)."Lymeborreliosis:detectingthegreatimitator".TheJournaloftheAmericanOsteopathicAssociation.91(6):573–4,577–8.doi:10.1515/jom-1991-910610.PMID 1874654.S2CID 245118295. ^HildenbrandP,CravenDE,JonesR,NemeskalP(June2009)."Lymeneuroborreliosis:manifestationsofarapidlyemergingzoonosis".AJNR.AmericanJournalofNeuroradiology.30(6):1079–87.doi:10.3174/ajnr.A1579.PMC 7051319.PMID 19346313. ^WesterveltHJ,McCaffreyRJ(September2002)."NeuropsychologicalfunctioninginchronicLymedisease".NeuropsychologyReview.12(3):153–77.doi:10.1023/A:1020381913563.PMID 12428915.S2CID 2807397. ^DworkinRH,JohnsonRW,BreuerJ,et al.(2007)."Recommendationsforthemanagementofherpeszoster".Clin.Infect.Dis.44Suppl1:S1–26.doi:10.1086/510206.PMID 17143845.S2CID 10894629. ^HalperinJJ(May2015)."ChronicLymedisease:misconceptionsandchallengesforpatientmanagement".InfectionandDrugResistance.8:119–128.doi:10.2147/IDR.S66739.PMC 4440423.PMID 26028977. ^abTarulliAW,RaynorEM(May2007)."Lumbosacralradiculopathy"(PDF).NeurologicClinics.25(2):387–405.doi:10.1016/j.ncl.2007.01.008.PMID 17445735.S2CID 15518713.Archivedfromtheoriginal(PDF)on20February2019. ^PachnerAR(1989)."NeurologicmanifestationsofLymedisease,thenew"greatimitator"".ReviewsofInfectiousDiseases.11Suppl6:S1482–6.doi:10.1093/clinids/11.Supplement_6.S1482.PMID 2682960.S2CID 3862308. ^BrandaJA,LinskeyK,KimYA,SteereAC,FerraroMJ(September2011)."Two-tieredantibodytestingforLymediseasewithuseof2enzymeimmunoassays,awhole-cellsonicateenzymeimmunoassayfollowedbyaVlsEC6peptideenzymeimmunoassay".ClinicalInfectiousDiseases.53(6):541–7.doi:10.1093/cid/cir464.PMID 21865190. ^abcdefghij"Preventingtickbitesonpeople".LymeDisease.CentersforDiseaseControlandPrevention.8March2019.Archivedfromtheoriginalon15June2019.Retrieved21May2019. ^ab"Aboutticks–preventativemeasures".Tick-bornediseases.CompanionVector-BorneDiseases.Archivedfromtheoriginalon7June2019.Retrieved21May2019. ^abcdefEisenL,EisenRJ(September2016)."Criticalevaluationofthelinkagebetweentick-basedriskmeasuresandtheoccurrenceofLymediseasecases".JMedEntomol.53(5):1050–1062.doi:10.1093/jme/tjw092.PMC 5777907.PMID 27330093. ^"Hostseeking".CVBD:CompanionVector-BorneDiseases.Archivedfromtheoriginalon16October2016.Retrieved8December2016. ^abc"Tipstopreventtickbytes".Insectrepellents.EnvironmentalProtectionAgency.15July2013.Archivedfromtheoriginalon15April2019.Retrieved21May2019. ^abcdefgh"ProtectionagainstMosquitoes,Ticks,&OtherArthropods".Travelers'Health.CentersforDiseaseControlandPrevention.Archivedfromtheoriginalon9May2019.Retrieved21May2019. ^abcMillerNJ,RainoneEE,DyerMC,GonzálezML,MatherTN(March2011)."Tickbiteprotectionwithpermethrin-treatedsummer-weightclothing".JMedEntomol.48(2):327–33.doi:10.1603/me10158.PMID 21485369. ^abEisenL,RoseD,ProseR,BreunerNE,DolanMC,ThompsonK,ConnallyN(October2017)."Bioassaystoevaluatenon-contactspatialrepellency,contactirritancyandacutetoxicityofpermethrin-treatedclothingagainstnymphalIxodesscapularisticks".TicksTickBorneDis.8(6):837–49.doi:10.1016/j.ttbdis.2017.06.010.PMC 5665650.PMID 28754599. ^DymondNL,SwiftIM(June2008)."Permethrintoxicityincats:aretrospectivestudyof20cases".AustVetJ.86(6):219–23.doi:10.1111/j.1751-0813.2008.00298.x.PMID 18498556. ^ab"Repellents:protectionagainstmosquitoes,ticksandotherarthropods".Insectrepellents.EnvironmentalProtectionAgency.9July2013.Archivedfromtheoriginalon20May2019.Retrieved21May2019. ^abcNguyenQD,VuMN,HebertAA(November2018)."Insectrepellents:anupdatedreviewfortheclinician".JAmAcadDermatol.doi:10.1016/j.jaad.2018.10.053.PMID 30395919.S2CID 53246686. ^abcdeStaffordKC(2007)."Tickmanagementhandbook(rev.ed.)"(PDF).Bulletins.ConnecticutAgriculturalExperimentStation.Archived(PDF)fromtheoriginalon3April2019.Retrieved21May2019. ^PiesmanJ,DolanMC(May2002)."ProtectionagainstlymediseasespirochetetransmissionprovidedbypromptremovalofnymphalIxodesscapularis(Acari:Ixodidae)".JournalofMedicalEntomology.39(3):509–12.doi:10.1603/0022-2585-39.3.509.PMID 12061448.S2CID 39805040. ^abcdef"Tickremovalandtesting".LymeDisease.CentersforDiseaseControlandPrevention.22April2019.Archivedfromtheoriginalon23November2017.Retrieved21May2019. ^ab"TickAllergy".2014.Archivedfromtheoriginalon14May2015.Retrieved30April2015. ^DuggalN,LuoE(May2017)."Cryotherapy:IsFreezingWartsanEffectiveTreatment?".Healthline.Archivedfromtheoriginalon4September2017.Retrieved21May2019. ^CelenzaA,RogersIR(2002)."The"KnotMethod"ofTickRemoval".Wilderness&EnvironmentalMedicine.13(2):179–180.doi:10.1580/1080-6032(2002)013[0181:ltte]2.0.co;2.PMID 12092975. ^Ghirga,Giovanni;Ghirga,Paolo(1September2010)."EffectiveTickRemovalWithaFishingLineKnot".Wilderness&EnvironmentalMedicine.21(3):270–271.doi:10.1016/j.wem.2010.04.005.ISSN 1080-6032.PMID 20832708. ^abcde"Preventingtickbitesintheyard".LymeDisease.CentersforDiseaseControlandPrevention.8March2019.Archivedfromtheoriginalon15June2019.Retrieved21May2019. ^"CDC–LymeDisease–NIOSHWorkplaceSafetyandHealthTopic".www.cdc.gov.3August2017.Archivedfromtheoriginalon13November2015.Retrieved3November2015. ^"Risks:LymeDisease|NIOSH|CDC".www.cdc.gov.14November2018.Archivedfromtheoriginalon26April2019.Retrieved26April2019. ^"Lymedisease".TheCentersforDiseaseControlandPrevention.12October2016.Archivedfromtheoriginalon17June2017.Retrieved22June2017. Thisarticleincorporates publicdomainmaterialfromwebsitesordocumentsoftheCentersforDiseaseControlandPrevention. ^RandPW,LubelczykC,HolmanMS,LacombeEH,SmithRP(July2004)."AbundanceofIxodesscapularis(Acari:Ixodidae)afterthecompleteremovalofdeerfromanisolatedoffshoreisland,endemicforLymeDisease".JournalofMedicalEntomology.41(4):779–84.doi:10.1603/0022-2585-41.4.779.PMID 15311475.S2CID 5853201. ^"Figure2:ChangesindeerdensityandcasesofLymediseaseinMumfordCove,Connecticut,1996–2004(CTDEPdata)"(PDF).ManagingUrbanDeerinConnecticut(2nd ed.).ConnecticutDepartmentofEnvironmentalProtection–WildlifeDivision.June2007.p. 4.Archived(PDF)fromtheoriginalon2June2013. ^PerkinsSE,CattadoriIM,TagliapietraV,RizzoliAP,HudsonPJ(August2006)."Localizeddeerabsenceleadstotickamplification".Ecology.87(8):1981–6.CiteSeerX 10.1.1.218.7660.doi:10.1890/0012-9658(2006)87[1981:LDALTT]2.0.CO;2.PMID 16937637. ^Stafford,KirbyC.(2004).TickManagementHandbook(PDF).ConnecticutAgriculturalExperimentStationandConnecticutDepartmentofPublicHealth.p. 46.Archived(PDF)fromtheoriginalon25October2007.Retrieved21August2007. ^abGernL,Estrada-PeñaA,FrandsenF,GrayJS,JaensonTG,JongejanF,KahlO,KorenbergE,MehlR,NuttallPA(March1998)."EuropeanreservoirhostsofBorreliaburgdorferisensulato".ZentralblattfürBakteriologie.287(3):196–204.doi:10.1016/S0934-8840(98)80121-7.PMID 9580423. ^abWodecka,Beata;Rymaszewska,Anna;Skotarczak,Bogumila(2013)."HostandpathogenDNAidentificationinbloodmealsofnymphalIxodesricinusticksfromforestparksandruralforestsofPoland".ExperimentalandAppliedAcarology.62(4):543–555.doi:10.1007/s10493-013-9763-x.PMC 3933768.PMID 24352572. ^JaensonTG,TälleklintL(September1992)."IncompetenceofroedeerasreservoirsoftheLymeborreliosisspirochete".JournalofMedicalEntomology.29(5):813–7.doi:10.1093/jmedent/29.5.813.PMID 1404260. ^TälleklintL,JaensonTG(1994)."TransmissionofBorreliaburgdorferis.l.frommammalreservoirstotheprimaryvectorofLymeborreliosis,Ixodesricinus(Acari:Ixodidae),inSweden".JournalofMedicalEntomology.31(6):880–886.doi:10.1093/jmedent/31.6.880.PMID 7815401. ^abWodeckaB,RymaszewskaA,SkotarczakB(April2014)."HostandpathogenDNAidentificationinbloodmealsofnymphalIxodesricinusticksfromforestparksandruralforestsofPoland".Experimental&AppliedAcarology.62(4):543–55.doi:10.1007/s10493-013-9763-x.PMC 3933768.PMID 24352572. ^OverzierE,PfisterK,HerbI,MahlingM,BöckG,SilaghiC(June2013)."Detectionoftick-bornepathogensinroedeer(Capreoluscapreolus),inquestingticks(Ixodesricinus),andinticksinfestingroedeerinsouthernGermany".TicksandTick-BorneDiseases.4(4):320–8.doi:10.1016/j.ttbdis.2013.01.004.PMID 23571115. ^PolandGA,JacobsonRM(March2001)."ThepreventionofLymediseasewithvaccine".Vaccine.19(17–19):2303–8.doi:10.1016/S0264-410X(00)00520-X.PMID 11257352. ^PolandGA(February2011)."VaccinesagainstLymedisease:Whathappenedandwhatlessonscanwelearn?".ClinicalInfectiousDiseases.52Suppl3:s253–8.doi:10.1093/cid/ciq116.PMID 21217172. ^Rowe,Claudia(13June1999)."LukewarmResponseToNewLymeVaccine".TheNewYorkTimes.Archivedfromtheoriginalon10February2012.Retrieved11July2008. ^abcAbbottA(February2006)."Lymedisease:uphillstruggle".Nature.439(7076):524–5.doi:10.1038/439524a.PMID 16452949.S2CID 4315588. ^"SoleLymeVaccineIsPulledOffMarket".TheNewYorkTimes.28February2002.Archivedfromtheoriginalon30August2010.Retrieved11July2008. ^abNigrovicLE,ThompsonKM(January2007)."TheLymevaccine:acautionarytale".EpidemiologyandInfection.135(1):1–8.doi:10.1017/S0950268806007096.PMC 2870557.PMID 16893489. ^abBrooks,DVM,WendyC."LymeDisease".VeterinaryInformationNetwork.Archivedfromtheoriginalon4April2015.Retrieved10February2012. ^"Anti-vaxxersstoppedthelastLymediseasevaccine.TheFDAhasjustfast-trackedanewone".Newsweek.25July2017.Archivedfromtheoriginalon25December2017.Retrieved25December2017. ^Brooks,David(6August2018)."ALymevaccineforhumansisgettingcloser,saysFrenchbiotechfirm".ConcordMonitor.Retrieved20July2021. ^AliceKlein.AnmRNAvaccinethatcausesared,itchyskinrashinresponsetobitesbyticksmayallowthemtoberemovedbeforetheytransmitLymedisease-causingbacteria.NewScientist,17November2021 ^Hathaway,Bill."NovelLymevaccineshowspromise".YaleUniversity.Retrieved13December2021.Comparedtonon-immunizedguineapigs,vaccinatedanimalsexposedtoinfectedticksquicklydevelopedrednessatthetickbitesite.NoneoftheimmunizedanimalsdevelopedLymediseaseiftickswereremovedwhenrednessdeveloped.Incontrast,abouthalfofthecontrolgroupbecameinfectedwithB.burgdorferiaftertickremoval.Whenasingleinfectedtickwasattachedtoimmunizedguineapigsandnotremoved,noneofvaccinatedanimalswereinfectedcomparedto60percentofcontrolanimals.However,protectionwanedinimmunizedguineapigsifthreeticksremainedattachedtotheanimal.Ticksinimmunizedanimalswereunabletofeedaggressivelyanddislodgedmorequicklythanthoseonguineapigsinthecontrolgroup. ^Sajid,Andaleeb;Matias,Jaqueline;Arora,Gunjan;Kurokawa,Cheyne;DePonte,Kathleen;Tang,Xiaotian;Lynn,Geoffrey;Wu,Ming-Jie;Pal,Utpal;Strank,NormaOlivares;Pardi,Norbert;Narasimhan,Sukanya;Weissman,Drew;Fikrig,Erol(2021)."mRNAvaccinationinducestickresistanceandpreventstransmissionoftheLymediseaseagent".ScienceTranslationalMedicine.13(620):eabj9827.doi:10.1126/scitranslmed.abj9827.PMID 34788080.S2CID 244375227. ^Pace,EJ;O'Reilly,M(1May2020)."TickborneDiseases:DiagnosisandManagement".AmericanFamilyPhysician.101(9):530–540.PMID 32352736. ^BerendeA,terHofstedeHJ,VosFJ,vanMiddendorpH,VogelaarML,TrompM,vandenHoogenFH,DondersAR,EversAW,KullbergBJ(March2016)."RandomizedTrialofLonger-TermTherapyforSymptomsAttributedtoLymeDisease".TheNewEnglandJournalofMedicine.374(13):1209–20.doi:10.1056/NEJMoa1505425.PMID 27028911. ^MichelleStephenson(4October2012)."OTCDrops:TellingtheTearsApart".ReviewofOphtalmology.JobsonMedicalInformationLLC.Archivedfromtheoriginalon17April2019.Retrieved16April2019. ^abcdeArvikarSL,SteereAC(June2015)."DiagnosisandTreatmentofLymeArthritis".InfectDisClinNorthAm.29(2):269–80.doi:10.1016/j.idc.2015.02.004.PMC 4443866.PMID 25999223. ^abcWormserGP,RamanathanR,NowakowskiJ,McKennaD,HolmgrenD,VisintainerP,DornbushR,SinghB,NadelmanRB(May2003)."DurationofantibiotictherapyforearlyLymedisease.Arandomized,double-blind,placebo-controlledtrial".AnnalsofInternalMedicine.138(9):697–704.doi:10.7326/0003-4819-138-9-200305060-00005.PMID 12729423.S2CID 3083800. ^StupicaD,LusaL,Ruzić-SabljićE,CerarT,StrleF(August2012)."Treatmentoferythemamigranswithdoxycyclinefor10daysversus15days".ClinInfectDis.55(3):343–50.doi:10.1093/cid/cis402.PMID 22523260. ^abDattwylerRJ,LuftBJ,KunkelMJ,FinkelMF,WormserGP,RushTJ,GrunwaldtE,AggerWA,FranklinM,OswaldD,CockeyL,MaladornoD(July1997)."CeftriaxonecomparedwithdoxycyclineforthetreatmentofacutedisseminatedLymedisease".NewEnglandJournalofMedicine.337(5):289–94.doi:10.1056/NEJM199707313370501.PMID 9233865. ^VrethemM,HellblomL,WidlundM,AhlM,DanielssonO,ErnerudhJ,ForsbergP(October2002)."Chronicsymptomsarecommoninpatientswithneuroborreliosis–aquestionnairefollow-upstudy".ActaNeurolScand.106(4):205–8.doi:10.1034/j.1600-0404.2002.01358.x.PMID 12225315.S2CID 42290158. ^BerglundJ,StjernbergL,OrnsteinK,Tykesson-JoelssonK,WalterH(2002)."5-yFollow-upstudyofpatientswithneuroborreliosis".ScandJInfectDis.34(6):421–5.doi:10.1080/00365540110080421.PMID 12160168.S2CID 28306612. ^abcClarkJR,CarlsonRD,SasakiCT,PachnerAR,SteereAC(November1985)."FacialparalysisinLymedisease".Laryngoscope.95(11):1341–5.doi:10.1288/00005537-198511000-00009.PMID 4058212.S2CID 85021. ^abcDotevallL,HagbergL(March1999)."SuccessfuloraldoxycyclinetreatmentofLymedisease-associatedfacialpalsyandmeningitis".ClinInfectDis.28(3):569–74.doi:10.1086/515145.PMID 10194080. ^KalishRA,KaplanRF,TaylorE,Jones-WoodwardL,WorkmanK,SteereAC(February2001)."EvaluationofstudypatientswithLymedisease,10-20-yearfollow-up".JInfectDis.183(3):453–60.doi:10.1086/318082.PMID 11133377. ^abcJowettN,GaudinRA,BanksCA,HadlockTA(June2017)."SteroiduseinLymedisease-associatedfacialpalsyisassociatedwithworselong-termoutcomes".Laryngoscope.127(6):1451–8.doi:10.1002/lary.26273.PMID 27598389.S2CID 25596860. ^NadelmanRB,HanincováK,MukherjeeP,LiverisD,NowakowskiJ,McKennaD,BrissonD,CooperD,BittkerS,MadisonG,HolmgrenD,SchwartzI,WormserGP(November2012)."DifferentiationofreinfectionfromrelapseinrecurrentLymedisease".NEnglJMed.367(20):1883–90.doi:10.1056/NEJMoa1114362.PMC 3526003.PMID 23150958. ^"Post-TreatmentLymeDiseaseSyndrome".CDC.3November2016.Archivedfromtheoriginalon17June2017. ^HigginsR(August2004)."Emergingorre-emergingbacterialzoonoticdiseases:bartonellosis,leptospirosis,Lymeborreliosis,plague".RevueScientifiqueetTechnique.23(2):569–81.doi:10.20506/rst.23.2.1503.PMID 15702720. ^BouattourA,GhorbelA,ChabchoubA,PosticD(2004)."[LymeborreliosissituationinNorthAfrica]"[LymeborreliosissituationinNorthAfrica].Archivesdel'InstitutPasteurdeTunis(inFrench).81(1–4):13–20.PMID 16929760. ^DsouliN,Younsi-KabachiiH,PosticD,NouiraS,GernL,BouattourA(July2006)."ReservoirroleoflizardPsammodromusalgirusintransmissioncycleofBorreliaburgdorferisensulato(Spirochaetaceae)inTunisia"(PDF).JournalofMedicalEntomology.43(4):737–42.doi:10.1603/0022-2585(2006)43[737:RROLPA]2.0.CO;2.PMID 16892633.Archived(PDF)fromtheoriginalon19July2018.Retrieved5July2019. ^HelmyN(August2000)."SeasonalabundanceofOrnithodoros(O.)savignyiandprevalenceofinfectionwithBorreliaspirochetesinEgypt".JournaloftheEgyptianSocietyofParasitology.30(2):607–19.PMID 10946521. ^FivazBH,PetneyTN(September1989)."Lymedisease--anewdiseaseinsouthernAfrica?".JournaloftheSouthAfricanVeterinaryAssociation.60(3):155–8.PMID 2699499. ^JowiJO,GathuaSN(May2005)."Lymedisease:reportoftwocases".EastAfricanMedicalJournal.82(5):267–9.doi:10.4314/eamj.v82i5.9318.PMID 16119758. ^LiM,MasuzawaT,TakadaN,IshiguroF,FujitaH,IwakiA,WangH,WangJ,KawabataM,YanagiharaY(July1998)."LymediseaseBorreliaspeciesinnortheasternChinaresemblethoseisolatedfromfareasternRussiaandJapan".AppliedandEnvironmentalMicrobiology.64(7):2705–9.Bibcode:1998ApEnM..64.2705L.doi:10.1128/AEM.64.7.2705-2709.1998.PMC 106449.PMID 9647853. ^MasuzawaT(December2004)."TerrestrialdistributionoftheLymeborreliosisagentBorreliaburgdorferisensulatoinEastAsia".JapaneseJournalofInfectiousDiseases.57(6):229–35.PMID 15623946.Archivedfromtheoriginalon22January2013. ^WalderG,LkhamsurenE,ShagdarA,et al.(May2006)."Serologicalevidencefortick-borneencephalitis,borreliosis,andhumangranulocyticanaplasmosisinMongolia".InternationalJournalofMedicalMicrobiology.296Suppl40:69–75.doi:10.1016/j.ijmm.2006.01.031.PMID 16524782. ^RizzoliA,HauffeH,CarpiG,VourcHG,NetelerM,RosaR(July2011)."LymeborreliosisinEurope".EuroSurveillance.16(27).PMID 21794218.Archivedfromtheoriginalon9July2011. ^SmithR,TakkinenJ(June2006)."Lymeborreliosis:Europe-widecoordinatedsurveillanceandactionneeded?".EuroSurveillance.11(6):E060622.1.doi:10.2807/esw.11.25.02977-en.PMID 16819127. ^LopesdeCarvalhoI,NúncioMS(2006)."LaboratorydiagnosisofLymeborreliosisatthePortugueseNationalInstituteofHealth(1990-2004)".EuroSurveillance.11(10):257–60.PMID 17130658.Archivedfromtheoriginalon17June2012. ^Vandekerckhove,Olivia;DeBuck,Emmy;VanWijngaerden,Eric(4May2021)."LymediseaseinWesternEurope:anemergingproblem?Asystematicreview".ActaClinicaBelgica.76(3):244–252.doi:10.1080/17843286.2019.1694293.ISSN 1784-3286.PMID 31739768.S2CID 208170787. ^abcd"EpidemiologyofLymeborreliosisintheUK".HPA.Archivedfromtheoriginalon10June2013.Retrieved15December2012. ^MuhlemannMF,WrightDJ(January1987)."EmergingpatternofLymediseaseintheUnitedKingdomandIrishRepublic".Lancet.1(8527):260–2.doi:10.1016/S0140-6736(87)90074-2.PMID 2880076.S2CID 25295954. ^abLymeDiseaseArchived15June2013attheWaybackMachineHansard11November1991 ^ab"TickLymediseaseoffyourholidaylist"(Pressrelease).HealthProtectionAgency.14April2011.Archivedfromtheoriginalon28April2011.Retrieved29March2013. ^"ConcernaboutriseinLymediseasecases".LymeDiseaseAction.15December2011.Archivedfromtheoriginalon19June2013.Retrieved15December2012. ^Cassidy,Frank(14March2011)."TaysiderevealedasaLymediseasehotspotascasessoar".PressandJournal.Archivedfromtheoriginalon11March2016. ^"Lymedisease:Aclearandpresentdanger".RCN.28April2009.Archivedfromtheoriginalon29March2013.Retrieved15December2012. ^"GuidanceonPart2–NotifiableDiseases,NotifiableOrganismsandHealthRiskStates".Scotland.gov.uk.10September2012.Retrieved15December2012. ^LymeDiseaseArchived15June2013attheWaybackMachineHansard,3February1997 ^Tick-BorneDisease,RiskandRealitArchived20November2012attheWaybackMachineBADA-UK,WendyFox,2010 ^"Lymeborreliosisepidemiologyandsurveillance:May2013".HPA.Archivedfromtheoriginalon25November2015.Retrieved24November2015. ^"ZoonosesreportUK2009"(PDF).DEFRA.24January2011.Archived(PDF)fromtheoriginalon3November2012. ^OverviewTickBitePreventionWeekArchived10April2012attheWaybackMachine ^HaywoodGA,O'ConnellS,GrayHH(July1993)."Lymecarditis:aUnitedKingdomperspective".BritishHeartJournal.70(1):15–6.doi:10.1136/hrt.70.1.15.PMC 1025222.PMID 8037992. ^GuyEC,BatemanDE,MartynCN,HeckelsJE,LawtonNF(March1989)."Lymedisease:prevalenceandclinicalimportanceofBorreliaburgdorferispecificIgGinforestryworkers".Lancet.1(8636):484–6.doi:10.1016/S0140-6736(89)91377-9.PMID 2563850.S2CID 39557628. ^SmithFD,BallantyneR,MorganER,WallR(March2012)."EstimatingLymediseaseriskusingpetdogsassentinels".ComparativeImmunology,MicrobiologyandInfectiousDiseases.35(2):163–7.doi:10.1016/j.cimid.2011.12.009.PMID 22257866.Laysummary–BristolUniversity(25January2012). ^Roberts,Michelle(24January2012)."Lymediseaseriskfromdogs'higherthanthought'".BBCNews.Archivedfromtheoriginalon31January2012. ^"TheLondonclimatechangeadaptationstrategy-Draftreport"(PDF).GreaterLondonAuthority.August2008.Archivedfromtheoriginal(PDF)on17August2012. ^BrownsteinJS,HolfordTR,FishD(March2005)."EffectofClimateChangeonLymeDiseaseRiskinNorthAmerica".EcoHealth.2(1):38–46.doi:10.1007/s10393-004-0139-x.PMC 2582486.PMID 19008966. ^abKillileaME,SweiA,LaneRS,BriggsCJ,OstfeldRS(June2008)."Spatialdynamicsoflymedisease:areview"(PDF).EcoHealth.5(2):167–95.CiteSeerX 10.1.1.580.8928.doi:10.1007/s10393-008-0171-3.PMID 18787920.S2CID 13545850.Archived(PDF)fromtheoriginalon8September2015. ^BCMinistryofAgriculture."TicksandHumansinBritishColumbia".Agf.gov.bc.ca.Archivedfromtheoriginalon3January2013.Retrieved15December2012. ^"LymeDiseaseFactSheet".Phac-aspc.gc.ca.4July2012.Archivedfromtheoriginalon27December2012.Retrieved15December2012. ^OgdenNH,LindsayLR,MorshedM,SockettPN,ArtsobH(June2009)."TheemergenceofLymediseaseinCanada".CMAJ.180(12):1221–4.doi:10.1503/cmaj.080148.PMC 2691438.PMID 19506281. ^LeightonPA,KoffiJK,PelcatY,LindsayLR,OgdenNH(2012)."Predictingthespeedoftickinvasion:AnempiricalmodelofrangeexpansionfortheLymediseasevectorIxodesscapularisinCanada".J.Appl.Ecol.49(2):457–64.doi:10.1111/j.1365-2664.2012.02112.x.S2CID 16921155. ^Gordillo-PérezG,TorresJ,Solórzano-SantosF,deMartinoS,LipskerD,VelázquezE,RamonG,OnofreM,JaulhacB(October2007)."BorreliaburgdorferiinfectionandcutaneousLymedisease,Mexico".EmergingInfectiousDiseases.13(10):1556–8.doi:10.3201/eid1310.060630.PMC 2851501.PMID 18258006. ^ab"ReportedcasesofLymediseasebystateorlocality,2005–2014†".cdc.gov.6November2017.Archivedfromtheoriginalon4May2012. ^"HowmanypeoplegetLymedisease?".cdc.gov.21December2018.Archivedfromtheoriginalon13October2014. ^CDC(4January2012)."ReportedLymediseasecasesbystate,2000-2010".CentersforDiseaseControlandPrevention(CDC).Archivedfromtheoriginalon4May2012.Retrieved29April2012. ^CentersforDiseaseControlPrevention(CDC)(June2007)."Lymedisease—UnitedStates,2003–2005".MMWR.MorbidityandMortalityWeeklyReport.56(23):573–6.PMID 17568368.Archivedfromtheoriginalon19November2012. ^BaconRM,KugelerKJ,MeadPS(October2008)."SurveillanceforLymedisease--UnitedStates,1992-2006".MMWR.SurveillanceSummaries.57(10):1–9.PMID 18830214.Archivedfromtheoriginalon10November2012. ^abRobbins,Jim(20May2003)."MontanaLabTriestoIdentifyTick-BorneDisease".TheNewYorkTimes.Archivedfromtheoriginalon3September2017. ^"LymeDiseaseData"Archived30April2012attheWaybackMachine.CentersforDiseaseControlandPrevention(CDC). ^"Lymedisease(Borreliaburgdorferi)2011casedefinition".U.S.CentersforDiseaseControlandPrevention.Archivedfromtheoriginalon22April2012. ^ab"Lymedisease(Borreliaburgdorferi)2008casedefinition".U.S.CentersforDiseaseControlandPrevention.Archivedfromtheoriginalon12June2012. ^abSwansonKI,NorrisDE(2007)."DetectionofBorreliaburgdorferiDNAinlizardsfromSouthernMaryland".VectorBorneandZoonoticDiseases.7(1):42–9.doi:10.1089/vbz.2006.0548.PMC 4128253.PMID 17417956. ^RichterD,MatuschkaFR(July2006)."PerpetuationoftheLymediseasespirocheteBorrelialusitaniaebylizards".AppliedandEnvironmentalMicrobiology.72(7):4627–32.Bibcode:2006ApEnM..72.4627R.doi:10.1128/AEM.00285-06.PMC 1489336.PMID 16820453. ^GieryST,OstfeldRS(June2007)."TheroleoflizardsintheecologyofLymediseaseintwoendemiczonesofthenortheasternUnitedStates".TheJournalofParasitology.93(3):511–7.doi:10.1645/GE-1053R1.1.PMID 17626342.S2CID 42617030. ^AmoreG,TomassoneL,GregoE,RagagliC,BertolottiL,NebbiaP,RosatiS,MannelliA(March2007)."BorrelialusitaniaeinimmatureIxodesricinus(Acari:Ixodidae)feedingoncommonwalllizardsinTuscany,centralItaly".JournalofMedicalEntomology.44(2):303–7.doi:10.1603/0022-2585(2007)44[303:BLIIIR]2.0.CO;2.PMID 17427701. ^MajláthováV,MajláthI,DerdákováM,VíchováB,Pet'koB(December2006)."Borrelialusitaniaeandgreenlizards(Lacertaviridis),KarstRegion,Slovakia".EmergingInfectiousDiseases.12(12):1895–901.doi:10.3201/eid1212.060784.PMC 3291370.PMID 17326941. ^"STARIorLyme?".CentersforDiseaseControlandPrevention.19November2018.Archivedfromtheoriginalon12November2019. ^LymediseasefactsheetAnalysisofCDCdataonVoxHealth.Retrievedon2013-30-1 ^MantovaniE,CostaIP,GauditanoG,BonoldiVL,HiguchiML,YoshinariNH(April2007)."DescriptionofLymedisease-likesyndromeinBrazil.IsitanewtickbornediseaseorLymediseasevariation?".BrazilianJournalofMedicalandBiologicalResearch.40(4):443–56.doi:10.1590/S0100-879X2006005000082.PMID 17401487. ^YoshinariNH,OyafusoLK,MonteiroFG,deBarrosPJ,daCruzFC,FerreiraLG,BonasserF,BaggioD,CossermelliW,et al.(1993)."[Lymedisease.ReportofacaseobservedinBrazil]"[Lymedisease.ReportofacaseobservedinBrazil].RevistadoHospitaldasClinicas(inPortuguese).48(4):170–4.PMID 8284588. ^HoenAG,MargosG,BentSJ,Diuk-WasserMA,BarbourA,KurtenbachK,FishD(September2009)."PhylogeographyofBorreliaburgdorferiintheeasternUnitedStatesreflectsmultipleindependentLymediseaseemergenceevents".ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica.106(35):15013–8.Bibcode:2009PNAS..10615013H.doi:10.1073/pnas.0903810106.JSTOR 40484546.PMC 2727481.PMID 19706476.Laysummary–YaleNews(10August2009). ^Josselyn,John(1670).AnAccountofTwoVoyagestoNew-EnglandMadeduringtheYears1638,1663.Archivedfromtheoriginalon25June2013.page92 ^abDrymon,MM(2008).Disguisedasthedevil:howLymediseasecreatedwitchesandchangedhistory.pp. 51–52.ISBN 978-0-615-20061-3. ^SummertonN(1995)."Lymediseaseintheeighteenthcentury".BMJ.311(7018):1478.doi:10.1136/bmj.311.7018.1478.S2CID 70661702. ^Hall,StephenS(November2011)."IcemanAutopsy".NationalGeographic.Archivedfromtheoriginalon19October2011.Retrieved17October2011. ^abMarcus,Karl(1910)."VerhandlungenderdermatologischenGesellschaftzuStockholm".Arch.Dermatol.Syph.101(2–3):403–06.doi:10.1007/BF01832773.S2CID 46704791. ^BurckhardtJL(1911)."ZurFragederFollikel-undKeimzentrenbildunginderHaut".Frankf.Z.Pathol.(inGerman).6:352–59. ^Edlow,JonathanA(2003).Bull's-eye:unravelingthemedicalmysteryofLymedisease.YaleUniversityPress.ISBN 978-0-300-09867-9.page191. ^HellerströmS(1930)."ErythemachronicummigransAfzelii".ActaDerm.-Venerol.(inGerman).11:315–21. ^LenhoffC(1948)."Spirochetesinaetiologicallyobscurediseases".ActaDerm.-Venerol.28(3):295–324.PMID 18891989. ^ThyressonN(1949)."Thepenicillintreatmentofacrodermatitisatrophicanschronica(Herxheimer)".ActaDermato-Venereologica.29(6):572–621.PMID 18140373. ^BianchiGE(1950)."[Penicillintherapyoflymphocytoma]"[Penicillintherapyoflymphocytoma].Dermatologica(inGerman).100(4–6):270–3.doi:10.1159/000257185.PMID 15421023. ^PaschoudJM(1954)."[Lymphocytomaaftertickbite]"[Lymphocytomaaftertickbite].Dermatologica(inGerman).108(4–6):435–7.PMID 13190934. ^ScrimentiRJ(July1970)."Erythemachronicummigrans".ArchivesofDermatology.102(1):104–5.doi:10.1001/archderm.102.1.104.PMID 5497158. ^BorchersAT,KeenCL,HuntleyAC,GershwinME(February2015)."Lymedisease:arigorousreviewofdiagnosticcriteriaandtreatment".JournalofAutoimmunity.57:82–115.doi:10.1016/j.jaut.2014.09.004.PMID 25451629. ^Weir,William(19September2013)."LymeDiseasePioneerStephenMalawistaDies".HartfordCourant.Archivedfromtheoriginalon14October2013.Retrieved14October2013. ^SternbachG,DibbleCL(1996)."WillyBurgdorfer:Lymedisease".TheJournalofEmergencyMedicine.14(5):631–4.doi:10.1016/S0736-4679(96)00143-6.PMID 8933327. ^BologniaJL,JorizzoJL,RapiniRP(2007).Dermatology(2nd ed.).St.Louis:Mosby.ISBN 978-1-4160-2999-1.[page needed] ^MastWE,BurrowsWM(November1976)."Erythemachronicummigransand"lymearthritis"".JAMA.236(21):2392d–2392.doi:10.1001/jama.236.21.2392d.PMID 989847. ^SteereAC,MalawistaSE,SnydmanDR,ShopeRE,AndimanWA,RossMR,SteeleFM(1977)."Lymearthritis:anepidemicofoligoarticulararthritisinchildrenandadultsinthreeconnecticutcommunities".ArthritisandRheumatism.20(1):7–17.doi:10.1002/art.1780200102.PMID 836338. ^"FactsheetaboutBorreliosis".EuropeanCentreforDiseasePreventionandControl.Archivedfromtheoriginalon27September2019.Retrieved30January2020. ^"WHO|LymeBorreliosis(Lymedisease)".WHO.Archivedfromtheoriginalon29November2019.Retrieved30January2020. ^SteereAC,HutchinsonGJ,RahnDW,SigalLH,CraftJE,DeSannaET,MalawistaSE(July1983)."TreatmentoftheearlymanifestationsofLymedisease".AnnalsofInternalMedicine.99(1):22–6.doi:10.7326/0003-4819-99-1-22.PMID 6407378. ^BurgdorferW(1984)."DiscoveryoftheLymediseasespirocheteanditsrelationtotickvectors".TheYaleJournalofBiologyandMedicine.57(4):515–20.PMC 2590008.PMID 6516454. ^BurgdorferW,BarbourAG,HayesSF,BenachJL,GrunwaldtE,DavisJP(June1982)."Lymedisease-atick-bornespirochetosis?".Science(Submittedmanuscript).216(4552):1317–9.Bibcode:1982Sci...216.1317B.doi:10.1126/science.7043737.PMID 7043737.Archivedfromtheoriginalon30January2020.Retrieved4September2018. ^LuftBJ,VolkmanDJ,HalperinJJ,DattwylerRJ(1988)."NewchemotherapeuticapproachesinthetreatmentofLymeborreliosis".AnnalsoftheNewYorkAcademyofSciences.539(1):352–61.Bibcode:1988NYASA.539..352L.doi:10.1111/j.1749-6632.1988.tb31869.x.PMID 3056203.S2CID 25939418. ^DattwylerRJ,VolkmanDJ,ConatySM,PlatkinSP,LuftBJ(December1990)."Amoxycillinplusprobenecidversusdoxycyclinefortreatmentoferythemamigransborreliosis".Lancet.336(8728):1404–6.doi:10.1016/0140-6736(90)93103-V.PMID 1978873.S2CID 7314488. ^RibeiroJM,MatherTN,PiesmanJ,SpielmanA(March1987)."DisseminationandsalivarydeliveryofLymediseasespirochetesinvectorticks(Acari:Ixodidae)".JournalofMedicalEntomology.24(2):201–5.doi:10.1093/jmedent/24.2.201.PMID 3585913. ^LoGiudiceK,OstfeldRS,SchmidtKA,KeesingF(January2003)."Theecologyofinfectiousdisease:effectsofhostdiversityandcommunitycompositiononLymediseaserisk".ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica.100(2):567–71.Bibcode:2003PNAS..100..567L.doi:10.1073/pnas.0233733100.PMC 141036.PMID 12525705. ^PatzJA,DaszakP,TaborGM,AguirreAA,PearlM,EpsteinJ,WolfeND,KilpatrickAM,FoufopoulosJ,MolyneuxD,BradleyDJ(July2004)."Unhealthylandscapes:Policyrecommendationsonlandusechangeandinfectiousdiseaseemergence".EnvironmentalHealthPerspectives.112(10):1092–8.doi:10.1289/ehp.6877.PMC 1247383.PMID 15238283. ^KhasnisAA,NettlemanMD(2005)."Globalwarmingandinfectiousdisease".ArchivesofMedicalResearch.36(6):689–96.doi:10.1016/j.arcmed.2005.03.041.PMID 16216650. ^FederHM,JohnsonBJ,O'ConnellS,ShapiroED,SteereAC,WormserGP,AggerWA,ArtsobH,AuwaerterP,DumlerJS,BakkenJS,BockenstedtLK,GreenJ,DattwylerRJ,MunozJ,NadelmanRB,SchwartzI,DraperT,McSweeganE,HalperinJJ,KlempnerMS,KrausePJ,MeadP,MorshedM,PorwancherR,RadolfJD,SmithRP,SoodS,WeinsteinA,WongSJ,ZemelL(October2007)."Acriticalappraisalof"chronicLymedisease"".TheNewEnglandJournalofMedicine.357(14):1422–30.doi:10.1056/NEJMra072023.PMID 17914043.S2CID 35285261. ^""ChronicLymeDisease"FactSheet".NationalInstituteofAllergyandInfectiousDiseases.17April2009.Archivedfromtheoriginalon15December2012. ^MarquesA(June2008)."ChronicLymedisease:areview".InfectiousDiseaseClinicsofNorthAmerica.22(2):341–60,vii–viii.doi:10.1016/j.idc.2007.12.011.PMC 2430045.PMID 18452806. ^MacBeth,Braden(8April2019)."AReviewofUnderOurSkin,ACultClassic".Science-BasedMedicine.Retrieved10September2021. ^abLittleSE,HeiseSR,BlagburnBL,CallisterSM,MeadPS(April2010)."LymeborreliosisindogsandhumansintheUSA".TrendsinParasitology.26(4):213–8.doi:10.1016/j.pt.2010.01.006.PMID 20207198. ^abKrupkaI,StraubingerRK(November2010)."Lymeborreliosisindogsandcats:background,diagnosis,treatmentandpreventionofinfectionswithBorreliaburgdorferisensustricto".TheVeterinaryClinicsofNorthAmerica.SmallAnimalPractice.40(6):1103–19.doi:10.1016/j.cvsm.2010.07.011.PMID 20933139. ^Hahn,Jeffrey."TicksandTheirControl".RegentsoftheUniversityofMinnesota.Archivedfromtheoriginalon25February2012.Retrieved19February2012. ^"GlomerularDisease".TheMerckVeterinaryManual.Archivedfromtheoriginalon26June2017.Retrieved19May2017. ^Staubinger,PhD,R.(31May2000)."LymeDisease".SiriusDog.Archivedfromtheoriginalon23June2012.Retrieved10February2012. ^FatalcasesofLymediseasereportedinthemedicalliteratureinclude: KirschM,RubenFL,SteereAC,DurayPH,NordenCW,WinkelsteinA(May1988)."FataladultrespiratorydistresssyndromeinapatientwithLymedisease".JAMA.259(18):2737–9.doi:10.1001/jama.1988.03720180063034.PMID 3357244. OksiJ,KalimoH,MarttilaRJ,MarjamäkiM,SonninenP,NikoskelainenJ,ViljanenMK(December1996)."InflammatorybrainchangesinLymeborreliosis.Areportonthreepatientsandreviewofliterature".Brain.119(Pt6)(Pt6):2143–54.doi:10.1093/brain/119.6.2143.PMID 9010017. WaniekC,ProhovnikI,KaufmanMA,DworkAJ(1995)."Rapidlyprogressivefrontal-typedementiaassociatedwithLymedisease".TheJournalofNeuropsychiatryandClinicalNeurosciences.7(3):345–7.doi:10.1176/jnp.7.3.345.PMID 7580195. CaryNR,FoxB,WrightDJ,CutlerSJ,ShapiroLM,GraceAA(February1990)."FatalLymecarditisandendodermalheterotopiaoftheatrioventricularnode".PostgraduateMedicalJournal.66(772):134–6.doi:10.1136/pgmj.66.772.134.PMC 2429516.PMID 2349186. Thisarticleincorporates publicdomainmaterialfromtheCentersforDiseaseControlandPreventiondocument:"Post-TreatmentLymeDiseaseSyndrome". Furtherreading[edit] Ostfeld,Richard(2012).LymeDisease:TheEcologyofaComplexSystem.NewYork:OxfordUniversityPress.ISBN 978-0199928477. Barbour,AlanG.(2015).Lymedisease:whyit'sspreading,howitmakesyousick,andwhattodoaboutit.Baltimore.ISBN 9781421417219. Halperin,JohnJay,ed.(2018).Lymedisease:anevidence-basedapproach(2nd ed.).Wallingford,Oxfordshire,UK:CABI.ISBN 978-1786392077. Radolf,JustinD.;Samuels,D.Scott,eds.(2021).Lymediseaseandrelapsingfeverspirochetes:genomics,molecularbiology,hostinteractionsanddiseasepathogenesis.Poole,UK:Caister.ISBN 978-1913652616. Externallinks[edit] WikimediaCommonshasmediarelatedtoBorreliosis. LymediseaseorganizationsatCurlie CDC-LymeDisease LymeDiseaseTests–LabTestsOnline NIH–LymeDisease NICEGuidelines–LymeDisease ClassificationDICD-10:A69.2ICD-9-CM:088.81MeSH:D008193DiseasesDB:1531ExternalresourcesMedlinePlus:001319PatientUK:LymediseaseScholia:Q201989 vteTick-bornediseasesandinfestationsDiseasesBacterialinfectionsRickettsiales Anaplasmosis Boutonneusefever Ehrlichiosis(Humangranulocytic,Humanmonocytotropic,HumanE.ewingiiinfection) Scrubtyphus Spottedfeverrickettsiosis PacificCoasttickfever Americantickbitefever rickettsialpox RockyMountainspottedfever) Spirochaete Baggio–Yoshinarisyndrome Lymedisease Relapsingfeverborreliosis Thiotrichales Tularemia Viralinfections Bhanjavirus Bourbonvirus Coloradotickfever Crimean–Congohemorrhagicfever Heartlandbandavirus Kemerovotickborneviralfever KyasanurForestdisease Omskhemorrhagicfever Powassanencephalitis Severefeverwiththrombocytopeniasyndrome Teteorthobunyavirus Tick-borneencephalitis Protozoaninfections Babesiosis Otherdiseases Tickparalysis Alpha-galallergy Southerntick-associatedrashillness Infestations Tickinfestation SpeciesandbitesAmblyomma Amblyommaamericanum Amblyommacajennense Amblyommatriguttatum Dermacentor Dermacentorandersoni Dermacentorvariabilis Ixodes Ixodescornuatus Ixodesholocyclus Ixodespacificus Ixodesricinus Ixodesscapularis Ornithodoros Ornithodorosgurneyi Ornithodoroshermsi Ornithodorosmoubata Other Rhipicephalussanguineus vteBacterialdiseasesduetogramnegativenon-proteobacteria(BV4)SpirochaeteSpirochaetaceaeTreponema Treponemapallidum Syphilis/bejel Yaws Treponemacarateum(Pinta) Treponemadenticola Borrelia Borreliaburgdorferi/Borreliaafzelii Lymedisease Erythemamigrans Neuroborreliosis Borreliarecurrentis(Lousebornerelapsingfever) Borreliahermsii/Borreliaduttoni/Borreliaparkeri(Tickbornerelapsingfever) LeptospiraceaeLeptospira Leptospirainterrogans(Leptospirosis) ChlamydiaceaeChlamydia Chlamydiapsittaci(Psittacosis) Chlamydiapneumoniae Chlamydiatrachomatis Chlamydia Lymphogranulomavenereum Trachoma Bacteroidetes Bacteroidesfragilis Tannerellaforsythia Capnocytophagacanimorsus Porphyromonasgingivalis Prevotellaintermedia Fusobacteria Fusobacteriumnecrophorum(Lemierre'ssyndrome) Fusobacteriumnucleatum Fusobacteriumpolymorphum Streptobacillusmoniliformis(Rat-bitefever/Haverhillfever) vteBacterialskindiseaseGram+veFirmicutes Staphylococcus Staphylococcalscaldedskinsyndrome Impetigo Toxicshocksyndrome Streptococcus Impetigo CutaneousgroupBstreptococcalinfection Streptococcalintertrigo CutaneousStreptococcusiniaeinfection Erysipelas/Chronicrecurrenterysipelas Scarletfever Corynebacterium Erythrasma Listeriosis Clostridium Gasgangrene Dermatitisgangrenosa Mycoplasma ErysipeloidofRosenbach Actinobacteria Mycobacterium-related:Aquariumgranuloma Borderlinelepromatousleprosy Borderlineleprosy Borderlinetuberculoidleprosy Buruliulcer Erythemainduratum Histoidleprosy Lepromatousleprosy Leprosy Lichenscrofulosorum Lupusvulgaris Miliarytuberculosis Mycobacteriumavium-intracellularecomplexinfection Mycobacteriumhaemophiluminfection Mycobacteriumkansasiiinfection Papulonecrotictuberculid Primaryinoculationtuberculosis Rapidgrowingmycobacteriuminfection Scrofuloderma Tuberculosiscutisorificialis Tuberculosisverrucosacutis Tuberculouscellulitis Tuberculousgumma Tuberculoidleprosy Cutaneousactinomycosis Nocardiosis Cutaneousdiphtheriainfection Arcanobacteriumhaemolyticuminfection GroupJKcorynebacteriumsepsis Gram-veProteobacteria α:Endemictyphus Epidemictyphus Scrubtyphus NorthAsianticktyphus Queenslandticktyphus Flyingsquirreltyphus Trenchfever Bacillaryangiomatosis Africantickbitefever Americantickbitefever Rickettsiaaeschlimanniiinfection Rickettsialpox RockyMountainspottedfever Humangranulocytotropicanaplasmosis Humanmonocytotropicehrlichiosis Flea-bornespottedfever Japanesespottedfever Mediterraneanspottedfever FlindersIslandspottedfever Verrugaperuana Brill–Zinsserdisease Brucellosis Cat-scratchdisease Oroyafever Ehrlichiosisewingiiinfection β:Gonococcemia/Gonorrhea/Primarygonococcaldermatitis Melioidosis CutaneousPasteurellahemolyticainfection Meningococcemia Glanders Chromobacteriosisinfection γ:Pasteurellosis Tularemia Vibriovulnificus Rhinoscleroma Haemophilusinfluenzaecellulitis Pseudomonalpyoderma/Pseudomonashot-footsyndrome/Hottubfolliculitis/Ecthymagangrenosum/Greennailsyndrome Qfever Salmonellosis Shigellosis Plague Granulomainguinale Chancroid Aeromonasinfection ε:Helicobactercellulitis Other Syphilid Syphilis Chancre Yaws Pinta Bejel Chlamydiainfection Leptospirosis Rat-bitefever Lymedisease Lymphogranulomavenereum Unspecifiedpathogen Abscess Periapicalabscess Boil/furuncle Hospitalfurunculosis Carbuncle Cellulitis Paronychia/Pyogenicparonychia Perianalcellulitis Acutelymphadenitis Pilonidalcyst Pyoderma Folliculitis Superficialpustularfolliculitis Sycosisvulgaris Pimple Ecthyma Pittedkeratolysis Trichomycosisaxillaris Necrotizingfascitis Gangrene Chronicunderminingburrowingulcers Fourniergangrene Elephantiasisnostras Blisteringdistaldactylitis Botryomycosis Malakoplakia Gram-negativefolliculitis Gram-negativetoewebinfection Pyomyositis Blastomycosis-likepyoderma Bullousimpetigo Chroniclymphangitis Recurrenttoxin-mediatedperinealerythema Tick-bornelymphadenopathy Tropicalulcer AuthoritycontrolGeneral IntegratedAuthorityFile(Germany) Nationallibraries France(data) UnitedStates Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Lyme_disease&oldid=1062811059" Categories:LymediseaseBacterialdiseasesBacterium-relatedcutaneousconditionsMedicalcontroversiesNeurodegenerativedisordersTick-bornediseasesHiddencategories:AllarticleslackingreliablereferencesArticleslackingreliablereferencesfromJuly2013CS1errors:URLWebarchivetemplatewaybacklinksCS1:longvolumevalueCS1Polish-languagesources(pl)WikipediaarticlesincorporatingtextfromtheCentersforDiseaseControlandPreventionCS1French-languagesources(fr)CS1Portuguese-languagesources(pt)CS1German-languagesources(de)WikipediaarticlesneedingpagenumbercitationsfromMarch2013ArticleswithshortdescriptionShortdescriptionmatchesWikidataUsedmydatesfromSeptember2017ShortdescriptionisdifferentfromWikidataAllarticleswithunsourcedstatementsArticleswithunsourcedstatementsfromMay2021ArticleswithunsourcedstatementsfromMarch2013AllpagesneedingfactualverificationWikipediaarticlesneedingfactualverificationfromJuly2013CommonscategorylinkisonWikidataArticleswithCurlielinksArticleswithGNDidentifiersArticleswithBNFidentifiersArticleswithLCCNidentifiersWikipediamedicinearticlesreadytotranslateWikipediaemergencymedicinearticlesreadytotranslate Navigationmenu Personaltools NotloggedinTalkContributionsCreateaccountLogin Namespaces ArticleTalk Variants expanded collapsed Views ReadEditViewhistory More expanded collapsed Search Navigation MainpageContentsCurrenteventsRandomarticleAboutWikipediaContactusDonate Contribute HelpLearntoeditCommunityportalRecentchangesUploadfile Tools WhatlinkshereRelatedchangesUploadfileSpecialpagesPermanentlinkPageinformationCitethispageWikidataitem Print/export DownloadasPDFPrintableversion Inotherprojects WikimediaCommonsWikispecies Languages العربيةAsturianuБеларускаяБеларуская(тарашкевіца)БългарскиBosanskiCatalàČeštinaCymraegDanskDeutschEestiΕλληνικάEspañolEsperantoEuskaraفارسیFrançaisGaeilgeGalego한국어ՀայերենHrvatskiBahasaIndonesiaItalianoעבריתJawaҚазақшаລາວLatviešuLëtzebuergeschLietuviųMagyarമലയാളംBahasaMelayuNederlands日本語ଓଡ଼ିଆپښتوPolskiPortuguêsRomânăРусскийScotsSimpleEnglishSlovenčinaSlovenščinaСрпски/srpskiSrpskohrvatski/српскохрватскиSuomiSvenskaТатарча/tatarçaไทยTürkçeУкраїнськаTiếngViệtWalon吴语粵語中文 Editlinks
延伸文章資訊
- 1Lyme Disease
Unlike in eastern Canada, the rate of Lyme disease has remained low in BC. Page Content. tick. Th...
- 2Lyme Disease - Taiwan Centers for Disease Control
Lyme disease, or borreliosis, is caused by the bacterium Borrelia burgdorferi and is transmitted ...
- 3Lyme disease - Symptoms and causes - Mayo Clinic
In the United States, Lyme disease is caused by the bacteria Borrelia burgdorferi and Borrelia ma...
- 4Signs and Symptoms of Untreated Lyme Disease - CDC
Signs and Symptoms of Untreated Lyme Disease · Occurs in approximately 70 to 80 percent of infect...
- 5Lyme Disease - MSD Manual Professional Edition
Lyme disease is a tick-transmitted infection caused by the spirochete Borrelia species. Early sym...