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Zikavirusinfection:AnoverviewUpToDate
OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate
Zikavirusinfection:Anoverview
Author: A.DesireeLaBeaud,MD,MS
SectionEditor: MartinSHirsch,MD
DeputyEditor: ElinorLBaron,MD,DTMH
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Aug2016.|Thistopiclastupdated:Sep26,2016.
INTRODUCTIONZikavirusisanarthropodborneflavivirustransmittedbymosquitoes[14].Thevirusisrelatedtootherflavivirusesincluding
denguevirus,yellowfevervirus,andWestNilevirus.ClinicalmanifestationsofZikavirusinfectionoccurinapproximately20percentofpatientsand
includeacuteonsetoflowgradefeverwithmaculopapularpruriticrash,arthralgia(notablysmalljointsofhandsandfeet),orconjunctivitis
(nonpurulent).
NeurotropismofZikavirushasbeendemonstratedinvivoandinvitro[59].Zikavirusinfectionhasbeenassociatedwithneurologiccomplications
theseincludecongenitalmicrocephaly(inadditiontootherdevelopmentalproblemsamongbabiesborntowomeninfectedduringpregnancy),Guillain
Barrsyndrome,myelitis,andmeningoencephalitis[1012].(See'Complications'below.)
Currently,thereisanongoingZikavirusoutbreakintheAmericas,theCaribbean,andthePacifictheWorldHealthOrganization(WHO)hasstated
thatthevirusis"spreadingexplosively"[13]andhasdeclaredZikavirusanditsassociatedcomplicationsaPublicHealthEmergencyofInternational
Concern[14].
OnlineupdatesregardingZikavirusinfectionmaybeviewedatthefollowingwebsites:
PanAmericanHealthOrganization(PAHO)/WHOwebsite
UnitedStatesCentersforDiseaseControlandPrevention(CDC)website
EuropeanCentreforDiseasePreventionandControl(ECDC)website
GeneralissuesrelatedtoZikavirusepidemiologyandpreventionarereviewedhere.IssuesrelatedtoZikavirusinfectioninpregnantwomenand
infantswithcongenitalexposurearediscussedseparately.(See"Zikavirusinfection:Evaluationandmanagementofpregnantwomen".)
EPIDEMIOLOGY
GeographicdistributionOutbreaksofZikavirusinfectionhaveoccurredinAfrica,SoutheastAsia,andthePacificIslandscurrently,thereisan
ongoingZikavirusoutbreakintheAmericas,theCaribbean,andthePacific[1517].UpdatesregardingthegeographicdistributionofZikavirusmaybe
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viewedattheUnitedStatesCentersforDiseaseControlandPreventionwebsiteandthePanAmericanHealthOrganization/WorldHealthOrganization
website.
ZikavirusisnamedaftertheUgandanforestwhereitwasfirstisolatedfromarhesusmonkeyin1947[18].Thefirsthumancasesweredetectedin
1952inUgandaandTanzania.ThevirussubsequentlyspreadacrossequatorialAfricaandAsia,whereitwasassociatedwithsporadicinfections.The
firstmajorrecognizedoutbreakoccurredintheYapIslandsofMicronesiain2007morethan70percentofthepopulation3yearsofagewasinfected,
resultinginanestimated5000infectionsamongthetotalpopulationof6700[1921].AnotherlargeroutbreakoccurredinFrenchPolynesiain2013to
2014,whichaffectedabouttwothirdsofthepopulation,resultinginapproximately32,000infections[22,23].DuringtheoutbreakinFrenchPolynesia,3
percentofdonatedbloodsamplestestedpositiveforZikavirusbypolymerasechainreaction[24].
ZikavirusinfectionswerefirstdetectedintheWesternhemisphereinFebruary2014onChile'sEasterIsland[25].Zikavirusinfectionswere
subsequentlydetectedinBrazilinMay2015[25].Molecularanalyseshavesuggestedthatthevirusmayhavebeenintroducedearlier,inlate2013or
early2014[26].RegionswithmosquitobornetransmissionofZikavirusaresummarizedbelow.(See'Traveladvisoriesforpregnantwomen'below.)
IntheUnitedStates,mosquitobornetransmissionhasoccurredinFlorida,andimportedZikainfectionhasbeenreportedintravelers[2729].Inone
reportfromNewYorkCityincluding3605individualswithtravelassociatedexposurewhounderwentZikaviruslaboratorytestingbetweenJanuaryand
June2016,positiveresultswereobservedin182patients(5percentofcases),including20pregnantwomen[30].ThefirstcaseofZikarelated
congenitalmicrocephalyintheUnitedStateswasreportedinJanuary2016inHawaii,inababyborntoawomanwhohadresidedinBrazilduringher
pregnancy[31].ThefirstcaseofsexuallytransmittedZikavirusinfectionintheUnitedStateswasreportedinTexasinFebruary2016[32].
TraveladvisoriesforpregnantwomenGivenanassociationbetweenZikavirusexposureduringpregnancyandcongenitalmicrocephaly,a
numberofauthoritieshaveadvisedthatpregnantwomenavoidorconsiderpostponingtraveltoareasbelow6500feet(2000meters)wheremosquito
transmissionofZikavirusisongoingtheseareasaresummarizedbelow[3338].Regionsabove6500feet(2000meters)areexcludedfromtravel
precautions,sincethemosquitoesthattransmitZikavirusarerareintheselocationsandtheriskformosquitobornetransmissionofZikavirusis
minimal[38].
CountriesandterritorieswithlocalmosquitobornetransmissionofZikavirusincludeAnguilla,AntiguaandBarbuda,Argentina,Aruba,TheBahamas,
Barbados,Belize,Bolivia,Bonaire,Brazil,theBritishVirginIslands,CapeVerde,CaymanIslands,Colombia,CostaRica,Cuba,Curaao,Dominica,
DominicanRepublic,Ecuador,ElSalvador,Fiji,FrenchGuiana,Grenada,Guadeloupe,Guatemala,Guyana,Haiti,Honduras,Jamaica,Kosrae
(FederatedStatesofMicronesia),MarshallIslands,Martinique,Mexico,NewCaledonia,Nicaragua,Panama,PapuaNewGuinea,Paraguay,Peru,
Saba,Samoa,SaintBarthlemy,SaintLucia,SaintMartin,SaintVincentandtheGrenadines,Singapore,SintEustatius,SintMaarten,Suriname,
Tonga,TrinidadandTobago,TurksandCaicos,theUnitedStates,andVenezuela[34,39,40].
WithintheUnitedStates,mosquitobornetransmissionofZikavirusinfectionhasoccurredinFloridapregnantwomenareadvisedtoavoidtraveltoan
areaofMiamiBeach[41,42].TheWynwoodareaofMiamiwasanactivetransmissionareafromJune15toSeptember18,2016theadvisorywas
liftedafterthreemosquitoincubationperiodspassedwithnonewlocallytransmittedcasesofZikavirusinfection[41].Inaddition,mosquitoborneZika
virustransmissioninPuertoRicohasbeenextensive[43,44].ThereisalsomosquitobornetransmissionofZikavirusintheUnitedStatesterritoriesof
theVirginIslandsandAmericanSamoa.
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TransmissionZikavirusmaybetransmittedtohumansviathefollowing[24,32,4551]:
Biteofaninfectedmosquito
Maternalfetaltransmission
Sex(includingvaginal,anal,andoralsex)
Bloodproducttransfusion
Organtransplantation
Laboratoryexposure
Preventivemeasuresbasedonthevariousmodesoftransmissionarediscussedbelow.(See'Prevention'below.)
Theprimarymodeoftransmissionisviamosquitobites.ZikavirusiscarriedbytheAedesaegyptimosquito,whichlivesintropicalregionshowever,
theAedesalbopictusmosquito,whichlivesintemperateregions,isalsocapableofcarryingit(figure1andfigure2)[5255].Aedesmosquitoescan
alsotransmitdengueandchikungunyaviruses.(See'Mosquitoprotection'below.)
ZikavirusRNAhasbeendetectedinblood,urine,semen,saliva,femalegenitaltractsecretions,cerebrospinalfluid,amnioticfluid,andbreastmilk
[24,52,5662]:
BloodInnonpregnantindividualswithZikavirusinfection,ZikavirusRNAisdetectableintheserumforafewdaystoaweekZikavirusRNAis
detectableinwholebloodaslateas58daysfollowingonsetofillness[63].Inpregnancy,ZikavirusRNAhasbeendetectedintheserumaslateas
10weeksafteronsetofillness[64].
UrineZikavirusRNAhasbeendetectedinurineupto91daysafteronsetofillness[57,60,61,6567].Replicatingvirushasbeendetectedin
urineatthetimeofsymptomaticillness[68].
SemenZikavirusRNAhasbeendetectedinsemenupto188daysafteronsetofillnessitcanbedetectedinsemenwhennolongerdetectable
inblood[61,67,6971].Replicatingvirushasbeendetectedinsemen7daysafteronsetofillness[72].SexualtransmissionofZikavirusaslateas
41daysafteronsetofapartner'ssymptomshasbeendescribed[47,73].Theviralloadinsemenmaybehighinonereport,theviralloadin
semenmorethantwoweeksafteronsetofsymptomswasroughly100,000timesthatofbloodorurine[74].
Aprobablecaseofmaletofemalesexualtransmissioninvolvinganasymptomaticmalehasalsobeenreported[75].
SalivaZikavirusRNAhasbeendetectedinsalivaupto91daysafteronsetofillness[58,61,67].Replicatingvirushasbeendetectedinsalivaat
thetimeofsymptomaticillness[68].
FemalegenitaltractsecretionsZikavirusRNAhasbeendetectedinfemalegenitaltractsecretions(viagenital,endocervicalswabs,andcervical
mucus)duringsymptomaticillness[62].ZikavirusRNAhasalsobeendetectedincervicalmucus11daysafteronsetofillness,whenitwasno
longerdetectableinbloodorurine[62].
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Humantohumantransmissionapartfromsexualtransmissionhasbeendescribed[76].Themodeoftransmissioninthecasedescribedisuncertain
closecontactoccurredwhiletheindexpatientsviralloadwasveryhigh,anditispossiblethatbloodandbodyfluidsofpatientswithZikavirusdisease
couldbeinfectious.
Issuesrelatedtomaternalfetaltransmissionandbreastfeedingarediscussedseparately.(See"Zikavirusinfection:Evaluationandmanagementof
pregnantwomen",sectionon'Congenitalinfection'.)
TheWorldHealthOrganizationhasissuedrecommendationsforpreventionofZikavirusinfectionforindividualsplanningtotraveltoBrazilforthe
OlympicGamesinAugust2016[77].
CLINICALMANIFESTATIONSTheincubationperiodbetweenmosquitobiteandonsetofclinicalmanifestationsistypically2to14days.Theillness
isusuallymildsymptomsresolvewithintwotosevendays.Immunitytoreinfectionoccursfollowingprimaryinfection[78].Severediseaserequiring
hospitalizationisuncommon,andcasefatalityratesarelow[7983].
Symptomsandsigns
AdultsSymptomsandsignsofZikavirusinfectiontypicallyincludeacuteonsetoflowgradefever(37.8to38.5C),maculopapularpruriticrash,
arthralgia(notablythesmalljointsofhandsandfeet),andconjunctivitis(nonpurulent)clinicalillnessisconsistentwithZikavirusdiseaseiftwoormore
ofthesesymptomsarepresent[33,8486].Othercommonlyreportedclinicalmanifestationsincludemyalgia,headache,retroorbitalpain,andasthenia
[79].Lesscommonlyobservedsymptomsandsignsincludeabdominalpain,nausea,diarrhea,andmucousmembraneulcerations[87].
Thrombocytopenia,palatalpetechiae,anduveitishavebeendescribedincasereports[8892].
ClinicalmanifestationsofZikavirusinfectionoccurin20to25percentofindividualswhobecomeinfectedwithZikavirus.Outsideareaswithmosquito
transmission,thelikelihoodofZikavirusinfectionamongasymptomaticindividualsislow[93].
ChildrenTherangeofZikavirusinfectioninchildrenincludesintrauterineinfection(verticaltransmissionduringpregnancy),intrapartuminfection
(verticaltransmissionatthetimeofdelivery),andpostnatalinfection(transmissionviamosquitobites).Issuesrelatedtointrauterineandintrapartum
infectionarediscussedseparately.(See"Zikavirusinfection:Evaluationandmanagementofpregnantwomen".)
ClinicalmanifestationsininfantsandchildrenwithpostnatalinfectionaresimilartothefindingsseeninadultswithZikavirusinfection[20,94].Arthralgia
isdifficulttodetectininfantsandyoungchildrenandmaymanifestasirritability,walkingwithalimp,difficultymovingorrefusingtomoveanextremity,
painonpalpation,orpainwithactiveorpassivemovementoftheaffectedjoint[94].Thusfar,nodevelopmentalcomplicationshavebeenobservedin
otherwisehealthychildrenwithpostnatalZikavirusinfection[95,96].(See"Evaluationofthechildwithjointpainand/orswelling".)
ComplicationsZikavirusinfectionhasbeenassociatedwithcomplicationsincludingcongenitalmicrocephalyandfetallossesamongwomen
infectedduringpregnancy,aswellasneurologiccomplications.Issuesrelatedtocongenitalinfectionarediscussedseparately.(See"Zikavirus
infection:Evaluationandmanagementofpregnantwomen".)
GuillainBarrsyndromeSeveralcountriesintheAmericashavereportedunusualincreasesincasesofGuillainBarrsyndrome(GBS)in
parallelwiththeongoingZikavirusoutbreak[97100].AnincreaseintherateofGBSinassociationwithZikavirusinfectionhasalsobeenobservedin
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otherreports[56,101106].
AcasecontrolstudyinFrenchPolynesiaevaluatedtheassociationbetweenGBSandZikavirusinfectionduringthe2013to2014outbreak[105].
Casesincluded42patientsdiagnosedwithGBSonecontrolgroupincluded98patientswithnonfebrileillnesses(matchedforage,sex,and
residence),andasecondcontrolgroupincluded70patientswithZikavirusinfectionintheabsenceofneurologicalcomplications.Zikaimmunoglobulin
(Ig)Mwaspositivein93percentofGBScases(versus17percentofpatientsinthefirstcontrolgroup)serologicevidenceofpastdengueinfectionwas
similaramongallthreegroups.AntiglycolipidIgGantibodiesweredetectedinfewerthan50percentofGBScases,raisingthepossibilityofdirectviral
neurotoxicity.ResultsofnerveconductionstudieswereconsistentwiththeacutemotoraxonalneuropathytypeofGBSclinicalimprovementduring
followupsuggestedreversibleconductionfailure.SymptomsofZikavirusinfectionoccurredin88percentofpatientswithGBSthemedianinterval
betweenviralsyndromeandonsetofneurologicalsymptomswassixdays.AllGBScasesreceivedintravenousimmuneglobulin,38percentrequired
intensivecare,and29percentneededrespiratorycareallsurvived.TheincidenceofGBSduringtheoutbreakwasestimatedtobe2.4casesper
10,000Zikavirusinfections.
Issuesrelatedtodiagnosis,evaluation,andmanagementofGuillainBarrsyndromearediscussedfurtherseparately.(See"Clinicalfeaturesand
diagnosisofGuillainBarrsyndromeinadults"and"TreatmentandprognosisofGuillainBarrsyndromeinadults".)
OtherneurologiccomplicationsZikavirushasbeenassociatedwithotherneurologiccomplicationsincludingbrainischemia[81],myelitis
[107],andmeningoencephalitis[108,109].Theseentitiesarediscussedfurtherseparately.(See"Transversemyelitis"and"Viralencephalitisinadults".)
DIFFERENTIALDIAGNOSISThedifferentialdiagnosisofZikavirusinfectionincludes:
Otherviralcausesofarthritis:
DenguefeverDenguevirusandZikavirusinfectionshavesimilarclinicalmanifestationsandaretransmittedbythesamemosquitovector.
However,dengueinfectionusuallypresentswithhighfever,severemusclepain,andheadacheandmayalsobeassociatedwithhemorrhage
unlikeZikainfection,dengueistypicallynotassociatedwithconjunctivitis(table1).CoinfectionwithZika,chikungunya,anddengueviruses
hasbeendescribed[110].Thediagnosisofdenguevirusinfectionisestablishedviaserology.(See"Clinicalmanifestationsanddiagnosisof
denguevirusinfection".)
ChikungunyaChikungunyavirusandZikaviruscausesimilarsymptomsandsignsandaretransmittedbythesamemosquitovector.
However,chikungunyausuallypresentswithhighfeverandintensejointpainaffectingthehands,feet,knees,andbackunlikeZikainfection,
chikungunyaistypicallynotassociatedwithconjunctivitis(table1).Chikungunyainfectioncanbedisabling,causingpatientstobendoversuch
thattheycannotwalk,andinfectedindividualsmaybeunabletoperformsimplemanualtasks.CoinfectionwithZika,chikungunya,and
dengueviruseshasbeendescribed[110].Thediagnosisofchikungunyavirusinfectionisestablishedviaserology.(See"Chikungunyafever".)
ParvovirusParvovirusinfectioncanpresentwithacuteandsymmetricarthritisorarthralgia,mostfrequentlyinvolvingthesmalljointsofthe
hands,wrists,knees,andfeet.Rashmayormaynotbepresent.Thediagnosisisestablishedviaserology.(See"Clinicalmanifestationsand
diagnosisofparvovirusB19infection".)
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RubellaClinicalmanifestationsofrubellaincludelowgradefeverandcoryza.Macularrashbeginsonthefaceandspreadstothetrunk,and
arthritisandlymphadenopathymaybepresent.Thediagnosisisestablishedviaserology.(See"Rubella".)
Anumberofothervirusesincludingenterovirus,adenovirus,andalphavirusesmayalsocausearthritisthesearediscussedfurther
separately.(See"Specificvirusesthatcausearthritis".)
MeaslesClinicalmanifestationsofmeaslesincludefever,cough,sorethroat,coryza,conjunctivitis,andlymphadenitis.Koplikspotsmayprecede
thegeneralizedrash.Thediagnosisisestablishedviaserology.(See"Clinicalmanifestationsanddiagnosisofmeasles".)
LeptospirosisLeptospirosisischaracterizedbyfever,rigors,myalgia,conjunctivalsuffusion,andheadache.Lesscommonsymptomsandsigns
includecough,nausea,vomiting,diarrhea,abdominalpain,andarthralgia.ItmaybedistinguishedfromZikavirusinfectionbythepresenceof
jaundice.Thediagnosisisestablishedviaserology.(See"Epidemiology,microbiology,clinicalmanifestations,anddiagnosisofleptospirosis".)
MalariaMalariaischaracterizedbyfever,malaise,nausea,vomiting,abdominalpain,diarrhea,myalgia,andanemia.Thediagnosisofmalariais
establishedbyvisualizationofparasitesonperipheralsmear.(See"Clinicalmanifestationsofmalariainnonpregnantadultsandchildren".)
RickettsialinfectionRickettsialinfectionswithsimilarmanifestationsasZikavirusinfectionincludeAfricantickbitefeverandrelapsingfever.
AfricantickbitefeverisobservedamongtravelerstoAfricaandtheCaribbeanandischaracterizedbyheadache,fever,myalgia,solitaryor
multipleescharswithregionallymphadenopathy,andgeneralizedrashthediagnosisisestablishedviaserology.Relapsingfeverischaracterized
byfever,headache,neckstiffness,arthralgia,myalgia,andnauseadiagnostictoolsincludedirectsmearandpolymerasechainreaction.(See
"Otherspottedfevergrouprickettsialinfections"and"Clinicalfeatures,diagnosis,andmanagementofrelapsingfever".)
GroupAStreptococcusClinicalmanifestationsofgroupAStreptococcusinfectionincludefever,myalgia,cutaneousmanifestations(cellulitis,
fasciitis),pharyngitis,andshock.Thediagnosisestablishedbypositiveculturesfromthebloodorothertissues.(See"GroupAstreptococcal
(Streptococcuspyogenes)bacteremiainadults".)
DIAGNOSISTheapproachtoZikavirusdiagnosismayvarydependingonavailableresourcestheapproachoutlinedinthefollowingsectionsmay
needtobetailoredtolocalcircumstances.
ThediagnosisofZikavirusinfectionshouldbesuspectedinindividualswithtypicalclinicalmanifestationsandrelevantepidemiologicexposure
(residenceinortraveltoanareawheremosquitobornetransmissionofZikavirusinfectionhasbeenreported,orunprotectedsexualcontactwitha
personwhomeetsthesecriteria).
IssuesrelatedtodiagnosisofZikavirusinfectioninsymptomaticadults(pregnantandnonpregnant)andchildrenwithpostnatalinfectionarediscussed
below.
IssuesrelatedtodiagnosisofZikavirusinfectioninasymptomaticpregnantwomenandinfantswithpossiblecongenitalZikavirusexposureare
discussedseparately.(See"Zikavirusinfection:Evaluationandmanagementofpregnantwomen".)
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CasedefinitionsThefollowinginterimcasedefinitionshavebeenissuedbytheWorldHealthOrganization(WHO)toprovideglobalstandardization
forclassificationandreportingofZikaviruscases[111].
Asuspectedcaseisapersonwitharash(maculopapular)and/orfever(37.8to38.5C)withatleastoneofthefollowingsymptoms(notexplained
byothermedicalconditions):arthralgia,arthritis,orconjunctivitis(nonpurulent/hyperemic).Asuspectedcaseshouldalsohaverelevant
epidemiologicexposure(residenceinortraveltoanareawheremosquitobornetransmissionofZikavirusinfectionhasbeenreported,or
unprotectedsexualcontactwithapersonwhomeetsthesecriteria),eventhoughepidemiologicexposureisnotincludedintheWHO
categorizationofasuspectedcase.
Aprobablecaseisasuspectedcasewithimmunoglobulin(Ig)MantibodyagainstZikavirus(withnoevidenceofinfectionwithotherflaviviruses)
andrelevantepidemiologicexposure(asdescribedabove).
AconfirmedcaseisapersonwithlaboratoryconfirmationofZikavirusinfection,eitherbydetectionofviralRNAorantigeninserumorother
samplesorbydetectionofZikaIgMantibodyandapositiveZikavirusplaquereductionneutralizationtest(PRNT).PRNTisneededtodetermine
whetherapositiveIgMantibodyresultagainstZikavirusreflectsrecentZikavirusinfectionorafalsepositiveresult.
GuidanceissuedbytheUnitedStatesCentersforDiseaseControlandPrevention(CDC)indicatesaPRNTtitergreaterthan10shouldbe
interpretedasevidenceofinfectionwithaspecificflaviviruswhenthePRNTtotheotherflavivirusestestedislessthan10(table2)[112].This
guidancereflectsamoreconservativeapproachtointerpretingPRNTthanpreviouslyprovidedbytheWHO(PRNTtiter20andPRNTtiter4
comparedwithotherflaviviruses)[111],sinceafourfoldhighertiterbyPRNTmaynotreliablydiscriminatebetweenZikavirusantibodiesandcross
reactingantibodiesinallindividualswhohavepriorinfectionorvaccinationagainstarelatedflavivirus.
Fornonpregnantpatientsresidinginareaswheremosquitotransmissionhasbeenestablished,thediagnosisofZikavirusinfectionmaybesuggested
basedonsymptomsandsignsandmaynotnecessarilywarrantlaboratorytesting,althoughdifferentiationfromotherillnesseswithsimilarclinical
manifestations(eg,dengue,chikungunya)maybedifficult[113,114].
Fornonpregnantpatientsresidinginareaswheremosquitotransmissionhasnotbeenestablishedandlaboratorytestingisavailable,diagnostictesting
iswarrantedforindividualswithcharacteristicsymptomsandsignsandrelevantepidemiologicexposure.(See'Symptomaticadults'below.)
Theapproachtodiagnosticevaluationofpregnantwomenandinfantswithintrauterineorintrapartuminfectionisdiscussedseparately.(See"Zikavirus
infection:Evaluationandmanagementofpregnantwomen".)
PatientgroupsIssuesrelatedtodiagnosisofZikavirusinfectioninsymptomaticadults(pregnantandnonpregnant)andsymptomaticchildrenwith
postnatalinfectionarediscussedbelow.ThereisnoroleforZikavirustestinginasymptomaticpatientswhoarenotpregnant.
IssuesrelatedtodiagnosisofZikavirusinfectioninasymptomaticpregnantwomenandinfantswithpossiblecongenitalZikavirusexposureare
discussedseparately.(See"Zikavirusinfection:Evaluationandmanagementofpregnantwomen".)
SymptomaticadultsThediagnosisofZikavirusinfectionisdefinitivelyestablishedviarealtimereversetranscriptionpolymerasechainreaction
(rRTPCR)forZikaviralRNA(inserumorurine)orZikavirusserology[33,84,112,115118]:
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Forindividualspresenting7daysafteronsetofsymptoms,diagnostictestingforZikavirusinfectionshouldincluderRTPCRofserumandurine
fordetectionofZikavirusRNA.rRTPCRtestingfordenguevirusandchikungunyavirusshouldalsobepursued.
SerumrRTPCRispositiveonlyforabriefwindow(threetosevendays)whentheinfectedpersonhasviremiatherefore,negativeresultscannot
excludeinfection.UrinerRTPCRmaybepositiveforupto14daysfollowingonsetofsymptoms.
Forindividualspresenting4to7daysafteronsetofsymptomswithnegativeZikavirusrRTPCR,Zikavirusserologictestingshouldbeperformed.
IfZikavirusIgMtestsresultsarepositive,equivocal,orinconclusive,testingforneutralizationantibodiesviaPRNTshouldbeperformedto
determinewhethertheZikavirusIgMreflectsrecentZikavirusinfectionorafalsepositiveresult.APRNTtitergreaterthan10shouldbe
interpretedasevidenceofinfectionwithaspecificflaviviruswhenthePRNTtotheothervirusestestedislessthan10(table2)[112].(See'Case
definitions'above.)
Testingfordenguevirusinfectionandchikungunyavirusinfectionshouldalsobepursued.AsinglelaboratoryPCRtestisavailablethroughthe
CDCandotherqualifiedlaboratoriestoevaluateforpresenceofZika,chikungunya,ordengueinfection[119].
Allserologicresultsshouldbeinterpretedwithcautionsincetherecanbecrossreactivitywithotherflaviviruses(includingdenguevirusandWest
Nilevirus).CrossreactivitymayalsobeobservedinindividualswhohavebeenvaccinatedagainstyellowfeverorJapaneseencephalitis[120].
Issuesrelatedtodiagnosisofdenguevirusandchikungunyavirusarediscussedseparately.(See"Clinicalmanifestationsanddiagnosisofdengue
virusinfection"and"Chikungunyafever",sectionon'Diagnosis'.)
Forindividualspresenting8to14daysaftertheonsetofsymptoms,diagnostictestingforZikavirusinfectionshouldincludeurinerRTPCRfor
detectionofZikavirusRNAaswellasZikavirusserologictesting(ZikavirusIgMandPRNT).
Forindividualspresenting15daysto12weeksafteronsetofsymptoms,diagnostictestingforZikavirusinfectionshouldconsistofZikavirus
serologictesting(ZikavirusIgMandPRNT).
Forindividualspresentingmorethan12weeksafteronsetofsymptoms,thereisnoroleforZikavirusserologictesting.
LaboratorytestingforZikavirusinfectionisperformedbythePanAmericanHealthOrganization/WHO,theCDCArboviralDiagnosticLaboratory,and
somestatehealthdepartments.IntheUnitedStates,statehealthdepartmentsshouldbecontactedtofacilitatediagnostictestingforZikavirus
infection.LaboratoryspecimensmayalsobesenttotheCDCArboviralDiagnosticLaboratoryinstructionsareavailableonline.Communicationshould
beinitiatedwiththelaboratoryviatelephone(19702216400)priortoshipmentofspecimens.
TheUnitedStatesFoodandDrugAdministrationhasalsoauthorizeduseofcommercialZikavirusserumPCRtestingandserologictestingbyqualified
laboratories[121,122].AsofAugust2016,commerciallaboratoriesperformingrRTPCRdonotperformZikaIgMenzymelinkedimmunosorbentassay
(ELISA)orconfirmatoryserologictesting(PRNT)[123].Therefore,ifpossible,providersshouldstoreaserumaliquotinarefrigerator(2to8C)for
subsequentZikaIgMELISAtestingiftherRTPCRassayisnegativeotherwise,collectionofanadditionalserumsamplemaybenecessary.
SymptomaticchildrenwithpostnatalinfectionPostnatalZikavirusinfection(eg,transmittedviamosquitobites)shouldbesuspectedinan
infantorchild<18yearswithrelevantepidemiologicexposureinthelasttwoweeksand2ofthefollowingmanifestations:fever,rash,conjunctivitis,or
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arthralgia[94].(See'Children'above.)
Thediagnosticapproachforthesechildrenisthesameasforadults,asdescribedabove.(See'Symptomaticadults'above.)
MANAGEMENTThereisnospecifictreatmentforZikavirusinfection.Managementconsistsofrestandsymptomatictreatment,includingdrinking
fluidstopreventdehydrationandadministrationofacetaminophentorelievefeverandpain[124].
Aspirinandothernonsteroidalantiinflammatorydrugs(NSAIDS)shouldbeavoideduntildengueinfectionhasbeenruledout,toreducetheriskof
hemorrhage.AspirinshouldnotbeusedinchildrenwithacuteviralillnessbecauseofitsassociationwithReyesyndrome.(See"Acutetoxicmetabolic
encephalopathyinchildren",sectionon'Reyesyndrome'.)
TheWorldHealthOrganizationhasissuedinitialguidanceonpsychosocialsupportforpatientsandfamiliesaffectedbyZikavirusinfectionand
associatedcomplications[125].
PREVENTIONThereisnovaccineforpreventionofZikavirusinfection.Modesoftransmissionaredescribedabove.(See'Transmission'above.)
Preventivemeasuresforpregnantandlactatingwomenandwomenofchildbearingpotentialarediscussedseparately.(See"Zikavirusinfection:
Evaluationandmanagementofpregnantwomen",sectionon'Prevention'.)
MosquitoprotectionIndividualsinareaswithriskfortransmissionshouldtakemeasurestoavoidmosquitobites,includingpersonalprotectionas
wellasenvironmentalcontrolmeasures[56].Aedesmosquitoesbiteduringthedaytimeaswellasattwilighttheybreedinstandingwater(particularly
manmadecontainers)[126].
Personalprotectivemeasuresinclude[56,127,128]:
Preventingmosquitobitesbywearinglongsleevesandlongpants,usinginsectrepellent,andstayingindoorsasfeasible(withairconditioning,
window/doorscreens,and/ormosquitonetstominimizecontactbetweenmosquitoesandpeople).(See"Preventionofarthropodandinsectbites:
Repellentsandothermeasures".)
IndividualswithZikavirusinfectionmayreducespreadofinfectiontoothersbyfollowingthesameprecautionstoavoidmosquitobitesduringthe
firstweekofillness(thelikelywindowofviremia).
AsymptomaticindividualswhohavetraveledtoanareawithZikavirusmosquitotransmissionandthenreturntoanareawithnoZikavirus
mosquitotransmissionshouldavoidmosquitobitesforthreeweeksafterreturn(theperiodduringwhichtheycouldbecomeviremic).
Environmentalcontrolmeasuresincludeidentificationandeliminationofpotentialmosquitobreedingsites.Mosquitolarvaebreedinstandingwater
therefore,residentsshouldbeinstructedtoavoidallowingstandingwatertocollectoutdoors(suchasinflowerpots,buckets,bottles,jars,andother
similarcontainersnearhouses).Domesticwatertanksshouldbecoveredsothatmosquitoescannotenter,anddrainsthatallowstagnantorstanding
watershouldbeeliminated.Localanddistricthealthdepartmentscanhelpfacilitatemitigationoftransmissionrisk.(See"Malariainendemicareas:
Epidemiology,prevention,andcontrol",sectionon'Mosquitocontrol'.)
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SexualtransmissionSexualtransmissionhasbeendescribedthedurationofviralpersistenceinsemenandinfemalegenitaltractsecretionsmay
beprolonged.(See'Transmission'above.)
Inallareas,menorwomenwithZikavirusinfectionorexposure(viatraveltomosquitotransmissionareasorsexualcontact)whohaveapregnant
partnershouldabstainfromunprotectedsexforthedurationofthepregnancy[50].(See"Malecondoms"and"Femalecondoms".)
WithinareasofZikavirusmosquitotransmission,itisprudentforindividualstoabstainfromsexualactivity(vaginal,anal,andoralsex)orusebarrier
protectionwhileactivetransmissionpersists[129].
OutsideareasofZikavirusmosquitotransmission,weareinagreementwithguidanceissuedbytheUnitedStatesCentersforDiseaseControland
Prevention(CDC)forcouplesinwhichoneorbothpartnershaveZikavirusinfectionorexposure,whichincludethefollowing[50,130]:
MenwithsymptomaticZikavirusinfection(confirmedorsuspected)shouldwaitatleastsixmonthsafteronsetofillnessbeforeunprotectedsex.
WomenwithsymptomaticZikavirusinfection(confirmedorsuspected)shouldwaitatleasteightweeksafteronsetofillnessbeforeunprotected
sex.
AsymptomaticmenandwomenwithZikavirusexposureshouldwaitatleasteightweeksafterZikavirusexposurebeforeunprotectedsex.
ThisguidancedifferssomewhatfromthatoftheWorldHealthOrganization(WHO),whichsuggeststhatmenandwomenoutsideareasofZika
transmissionwhohavetraveledtoareaswithactivetransmissionwaitatleastsixmonthsfollowingtheirreturnbeforeunprotectedsex,regardlessof
symptoms[131].TheWHOindicatesthatthisisaconservativerecommendation,basedinpartonthelimiteddataonthedurationandinfectivityofZika
virusinthesemenfollowinginitialinfection.(See'Transmission'above.)
IssuesrelatedtopreventionofZikavirusduringpregnancyarediscussedfurtherseparately.(See"Zikavirusinfection:Evaluationandmanagementof
pregnantwomen",sectionon'Prevention'.)
Blood/tissuedonationZikavirusistransmissibleviabloodproductsandorganortissuetransplantation[24,48].Issuesrelatedtodonorscreening
arediscussedfurtherseparately.(See"Blooddonorscreening:Medicalhistory",sectionon'Zikavirus'and"Blooddonorscreening:Laboratory
testing".)
TheUSFoodandDrugAdministration(FDA)hasissueddonordeferralrecommendationsforhematopoieticstemcells,tissues,anddonorgametes
therecommendationsdonotapplytosolidorgans[132].LivingdonorswithZikavirusinfectionorrelevantepidemiologicexposure(residenceinor
traveltoanareawheremosquitobornetransmissionofZikavirusinfectionhasbeenreported,orunprotectedsexualcontactwithapersonwhomeets
thesecriteria)shouldbeconsideredineligiblefordonationforsixmonths.DeceaseddonorswithZikavirusinfectionintheprecedingsixmonthsshould
bealsobeconsideredineligible.
NosocomialtransmissionTransmissionofZikavirusviaoccupationalexposureinahealthcaresettinghasnotbeendescribed.Standard
precautionsareappropriateforprotectionofhealthcarepersonnelandpatientsfromZikavirusinfectioninthesesettings[129,133].(See"General
principlesofinfectioncontrol",sectionon'Standardprecautions'.)
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INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and"BeyondtheBasics."TheBasics
patienteducationpiecesarewritteninplainlanguage,atthe5thto6thgradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatient
mighthaveaboutagivencondition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.
BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10thto12thgrade
readinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicstoyourpatients.(Youcanalso
locatepatienteducationarticlesonavarietyofsubjectsbysearchingon"patientinfo"andthekeyword(s)ofinterest.)
Basicstopics(see"Patienteducation:Zikavirusinfection(TheBasics)"and"Patienteducation:GuillainBarrsyndrome(TheBasics)")
SUMMARY
OutbreaksofZikavirusinfection,causedbyanemergingmosquitoborneflavivirus,haveoccurredinAfrica,SoutheastAsia,andthePacific
Islandscurrently,thereisanongoingZikavirusoutbreakintheAmericas.ZikavirusistransmittedtohumansviathebiteofaninfectedAedes
mosquito.Thistypeofmosquitousuallybitesduringthedaytimeandbreedsinstandingwater(particularlymanmadecontainers).(See
'Epidemiology'above.)
ClinicalmanifestationsofZikavirusinfectionincludeacuteonsetoflowgradefeverwithmaculopapularpruriticrash,arthralgia(notablysmalljoints
ofhandsandfeet),orconjunctivitis(nonpurulent)clinicalillnessisconsistentwithZikavirusdiseaseiftwoormoreofthesesymptomsarepresent.
Zikavirusinfectionhasalsobeenassociatedwithcongenitalmicrocephaly,fetalloss,andGuillainBarrsyndrome.(See'Clinicalmanifestations'
above.)
Theincubationperiodbetweenmosquitobiteandonsetofclinicalmanifestationsistypically2to14days.Theillnessisusuallymildclinical
manifestationsusuallyresolvewithintwotosevendays.Asymptomaticinfectioniscommonsymptomsdevelopin20to25percentofindividuals
whobecomeinfectedwithZikavirus.Onceapersonhasbeeninfected,heorsheislikelytobeprotectedfromfutureinfections.(See'Symptoms
andsigns'above.)
ThediagnosisofZikavirusinfectionshouldbesuspectedinindividualswithtypicalclinicalmanifestationsandrelevantepidemiologicexposure
(residenceinortraveltoanareawheremosquitobornetransmissionofZikavirusinfectionhasbeenreported,orunprotectedsexualcontactwith
apersonwhomeetsthesecriteria).(See'Diagnosis'above.)
ThediagnosisofZikavirusinfectionisestablishedviarealtimereversetranscriptionpolymerasechainreaction(rRTPCR)testingforZikaviral
RNA(inserumorurine)orserology.Theapproachtodiagnostictestingdependsonthetimingofpresentationafteronsetofsymptoms.(See
'Patientgroups'above.)
ThereisnospecifictreatmentforZikavirusinfectionandthereisnovaccineforprevention.Managementconsistsofsymptomatictreatment.
Preventivemeasuresincludepersonalprotectivemeasurestopreventmosquitobitesandinstitutionofmeasurestoeliminateandcontrolmosquito
breedingsites.(See'Management'aboveand'Mosquitoprotection'above.)
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SexualtransmissionofZikavirushasbeendescribed.Inallareas,menorwomenwithZikavirusinfectionorexposure(viatraveltomosquito
transmissionareasorsexualcontact)whohaveapregnantpartnershouldabstainfromunprotectedsexforthedurationofthepregnancy.Within
areasofZikavirusmosquitotransmission,itisprudentforindividualstoabstainfromsexualactivity(vaginal,anal,andoralsex)orusebarrier
protectionwhileactivetransmissionpersists.(See'Sexualtransmission'above.)
OutsideareasofZikavirusmosquitotransmission,guidanceforcouplesinwhichoneorbothpartnershaveZikavirusinfectionorexposure
includethefollowing(see'Sexualtransmission'above):
MenwithsymptomaticZikavirusinfection(confirmedorsuspected)shouldwaitatleastsixmonthsafteronsetofillnessbeforeunprotected
sex.
WomenwithsymptomaticZikavirusinfection(confirmedorsuspected)shouldwaitatleasteightweeksafteronsetofillnessbefore
unprotectedsex.
AsymptomaticmenandwomenwithZikavirusexposureshouldwaitatleasteightweeksafterZikavirusexposurebeforeunprotectedsex.
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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Topic106169Version108.0
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GRAPHICS
EstimatedrangeofAedesaegyptiandAedesalbopictusintheUnited
States
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Thesemapsshowareaswheremosquitoesareorhavebeenpreviouslyfound(basedonavarietyof
sources)andreflectestimatesofthepotentialrangeofAedesaegyptiandAedesalbopictusintheUnited
States.Thesemapsdonotshowexactlocationsornumbersofmosquitoeslivinginanareanordothey
representriskforspreadofdisease.
Reproducedfrom:CentersforDiseaseControlandPrevention.ZikaVirus:VectorSurveillanceandControl.
Availableat:http://www.cdc.gov/zika/vector/index.html(AccessedonMarch31,2016).
Graphic106382Version3.0
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GlobaldistributionofAedesaegyptiandAedesalbopictus
From:MussoD,GublerDJ.Zikavirus.ClinMicrobiolRev201629(3):487524.DOI:10.1128/CMR.0007215.Reproducedwithpermissionfrom
AmericanSocietyforMicrobiology.Copyright2016.
Graphic107582Version1.0
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Clinicalfeatures:Zikaviruscomparedwithdengueandchikungunya
Features
Zika
Dengue
Chikungunya
Fever
++
+++
+++
Rash
+++
++
Conjunctivitis
++
Arthralgia
++
+++
Myalgia
++
Headache
++
++
Hemorrhage
++
Shock
Reproducedfrom:CentersforDiseaseControlandPrevention.ZikavirusWhatcliniciansneedtoknow?ClinicianOutreachandCommunicationActivity(COCA)Call,
January26,2016.Availableat:http://emergency.cdc.gov/coca/ppt/2016/01_26_16_zika.pdf(AccessedFebruary1,2016).
Graphic106512Version1.0
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InterpretationofresultsofantibodytestingforsuspectedZikavirusinfection* UnitedStates,2016
Zikavirusanddenguevirus
IgMELISA
ZikavirusPRNT
DenguevirusPRNT
Interpretation
Positiveorequivocal(eitherassay)
10
<10
RecentZikavirusinfection
Positiveorequivocal(eitherassay)
<10
10
Recentdenguevirusinfection
Positiveorequivocal(eitherassay)
10
10
Recentflavivirusinfectionspecific
viruscannotbeidentified
InconclusiveinoneassayAND
inconclusiveornegativeintheother
10
<10
EvidenceofZikavirusinfectiontiming
cannotbedetermined
InconclusiveinoneassayAND
inconclusiveornegativeintheother
<10
10
Evidenceofdenguevirusinfection
timingcannotbedetermined
InconclusiveinoneassayAND
inconclusiveornegativeintheother
10
10
Evidenceofflavivirusinfection
specificvirusandtimingcannotbe
determined
Anyresult(eitherorbothassays)
<10
<10
NoevidenceofZikavirusordengue
virusinfection
PositiveforZikavirusANDnegativefor
denguevirus
Notyetperformed
Notyetperformed
PresumptiverecentZikavirusinfection
PositivefordenguevirusANDnegative
forZikavirus
Notyetperformed
Notyetperformed
Presumptiverecentdenguevirus
infection
PositiveforZikavirusANDpositivefor
denguevirus
Notyetperformed
Notyetperformed
Presumptiverecentflavivirusvirus
infection
Equivocal(eitherorbothassays)
Notyetperformed
Notyetperformed
Equivocalresults
InconclusiveinoneassayAND
inconclusiveornegativeintheother
Notyetperformed
Notyetperformed
Inconclusiveresults
NegativeforZikavirusANDnegative
fordenguevirus
Notindicated
Notindicated
NoevidenceofrecentZikavirusor
denguevirusinfection
ELISA:enzymelinkedimmunosorbentassayIgM:immunoglobulinMantibodiesPRNT:plaquereductionneutralizationtest.
*ForpersonswithsuspectedZikavirusdisease,Zikavirusrealtimereversetranscriptionpolymerasechainreaction(rRTPCR)shouldbeperformedonserum
specimenscollected<7daysafteronsetofsymptomsandonurinespecimenscollected<14daysafteronsetofsymptoms.
IntheabsenceofrRTPCRtesting,negativeIgMorneutralizingantibodytestinginspecimenscollected<7daysafterillnessonsetmightreflectcollectionbefore
developmentofdetectableantibodiesanddoesnotruleoutinfectionwiththevirusforwhichtestingwasconducted.
ZikaIgMpositiveresultisreportedas"presumptivepositive"todenotetheneedtoperformconfirmatoryPRNT.
ReportanypositiveorequivocalIgMZikaordengueresultstostateorlocalhealthdepartment.
Toresolvefalsepositiveresultsthatmightbecausedbycrossreactivityornonspecificreactivity,presumptivepositiveZikaIgMresultsshouldbeconfirmedwith
PRNTtitersagainstZika,dengue,andotherflavivirusestowhichthepersonmighthavebeenexposed.Inaddition,equivocalandinconclusiveresultsthatarenot
resolvedbyretestingalsoshouldhavePRNTtitersperformedtoruleoutafalsepositiveresult.
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Reproducedfrom:RabeIB,StaplesJE,VillanuevaJ,etal.InterimGuidanceforInterpretationofZikaVirusAntibodyTestResults.MMWRMorbidMortalWklyRep2016.
Graphic108362Version1.0
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