25/4/2016

Zikavirusinfection:Anoverview

OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate

Zikavirusinfection:Anoverview
Author
A.DesireeLaBeaud,MD,MS

SectionEditor
MartinSHirsch,MD

DeputyEditor
ElinorLBaron,MD,DTMH

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Mar2016.|Thistopiclastupdated:Apr20,2016.
INTRODUCTIONZikavirusisanarthropodborneflavivirustransmittedbymosquitoes[1,2].Thevirusis
relatedtootherflavivirusesincludingdenguevirus,yellowfevervirus,andWestNilevirus.Clinicalmanifestations
ofZikavirusinfectionoccurinapproximately20percentofpatientsandincludeacuteonsetoflowgradefever
withmaculopapularpruriticrash,arthralgia(notablysmalljointsofhandsandfeet),orconjunctivitis(nonpurulent).
NeurotropismofZikavirushasbeendemonstratedinvivoandinvitro[37].Zikavirusinfectionhasbeen
associatedwithneurologiccomplicationstheseincludecongenitalmicrocephaly(inadditiontoother
developmentalproblemsamongbabiesborntowomeninfectedduringpregnancy),GuillainBarrsyndrome,
myelitis,andmeningoencephalitis[810].(See'Complications'below.)
Currently,thereisanongoingZikavirusoutbreakintheAmericas,theCaribbean,andthePacifictheWorld
HealthOrganization(WHO)hasstatedthatthevirusis"spreadingexplosively"[11]andhasdeclaredZikavirus
anditsassociatedcomplicationsaPublicHealthEmergencyofInternationalConcern[12].
OnlineupdatesregardingZikavirusinfectionmaybeviewedatthefollowingwebsites:
PanAmericanHealthOrganization(PAHO)/WHOwebsite
UnitedStatesCentersforDiseaseControlandPrevention(CDC)website
EuropeanCentreforDiseasePreventionandControl(ECDC)website
GeneralissuesrelatedtoZikavirusepidemiologyandpreventionarereviewedhere,asareissuesrelatedtoZika
virusinfectioninnonpregnantadultsandchildrenwithpostnatalinfection.IssuesrelatedtoZikavirusinfectionin
pregnantwomenandinfantswithcongenitalexposurearediscussedseparately.(See"Zikavirusinfection:
Evaluationofpregnantwomenandinfants".)
EPIDEMIOLOGY
GeographicdistributionOutbreaksofZikavirusinfectionhaveoccurredinAfrica,SoutheastAsia,andthe
PacificIslandscurrently,thereisanongoingZikavirusoutbreakintheAmericas,theCaribbean,andthePacific
[1315].GivenanassociationbetweenZikavirusexposureduringpregnancyandcongenitalmicrocephaly,a
numberofauthoritieshaveadvisedthatpregnantwomenavoidorconsiderpostponingtraveltoareasbelow6500
feet(2000meters)wheremosquitotransmissionofZikavirusisongoing[1621].Updatesregardingthegeographic
distributionofZikavirusmaybeviewedattheUnitedStatesCentersforDiseaseControlandPreventionwebsite
andthePanAmericanHealthOrganization/WorldHealthOrganizationwebsite.
ZikavirusisnamedaftertheUgandanforestwhereitwasfirstisolatedinarhesusmonkeyin1947[22].Thefirst
humancasesweredetectedin1952inUgandaandTanzania.Thevirussubsequentlyspreadacrossequatorial
AfricaandAsia,whereitwasassociatedwithsporadicinfections.Thefirstmajorrecognizedoutbreakoccurredin
theYapIslandsofMicronesiain2007morethan70percentofthepopulation3yearsofagewasinfected,
resultinginanestimated5000infectionsamongthetotalpopulationof6700[2325].Anotherlargeroutbreak
occurredinFrenchPolynesiain2013to2014,whichaffectedabouttwothirdsofthepopulation,resultingin
approximately32,000infections[26,27].
ZikavirusinfectionswerefirstdetectedintheWesternhemisphereinFebruary2014onChile'sEasterIsland[28].
ZikavirusinfectionsweresubsequentlydetectedinBrazilinMay2015[28].Molecularanalyseshavesuggested
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thatthevirusmayhavebeenintroducedearlier,inlate2013orearly2014[29].
AsofApril2016,countrieswithautochthonous(mosquitoborne)circulationofZikavirusincludeAruba,Barbados,
Belize,Bolivia,Bonaire,Brazil,CapeVerde,Colombia,CostaRica,Cuba,Curaao,Dominica,Dominican
Republic,Ecuador,ElSalvador,Fiji,FrenchGuiana,Guadeloupe,Guatemala,Guyana,Haiti,Honduras,Jamaica,
Kosrae(FederatedStatesofMicronesia),MarshallIslands,Martinique,Mexico,NewCaledonia,Nicaragua,
Panama,Paraguay,SaintLucia,SaintMartin,SintMaarten,SaintVincentandtheGrenadines,Samoa,Suriname,
Tonga,TrinidadandTobago,andVenezuela[17,30,31].
Regionsabove6500feet(2000meters)areexcludedfromtravelprecautions,sincethemosquitoesthattransmit
ZikavirusarerareintheselocationsandtheriskformosquitobornetransmissionofZikavirusisminimal[21].
ZikavirusinfectionhasbeendetectedintheUnitedStatesterritoriesofPuertoRico,theUSVirginIslands,and
AmericanSamoa[3234].MosquitobornetransmissionofZikavirusinfectionhasnotyetbeenreportedinthe
continentalUnitedStates,butcasesofimportedZikainfectionhavebeenreportedinpregnantandnonpregnant
travelers[3537].ThefirstcaseofZikarelatedcongenitalmicrocephalyintheUnitedStateswasreportedin
January2016inHawaii,inababyborntoawomanwhohadresidedinBrazilduringherpregnancy[38].Acaseof
sexuallytransmittedZikavirusinfectionwasreportedinTexasinFebruary2016[39].
TransmissionZikavirusmaybetransmittedtohumansviathefollowing[3953]:
Biteofaninfectedmosquito
Maternalfetaltransmission
Sex(includingvaginal,anal,andoralsex)
Bloodtransfusion
Organtransplantation
Laboratoryexposure
Preventivemeasuresbasedonthevariousmodesoftransmissionarediscussedbelow.(See'Prevention'below.)
Theprimarymodeoftransmissionisviamosquitobites.ZikavirusiscarriedbytheAedesaegyptimosquito,
whichlivesintropicalregionshowever,theAedesalbopictusmosquito,whichlivesintemperateregions,isalso
capableofcarryingit(figure1andfigure2)[5457].Aedesmosquitoescanalsotransmitdengueandchikungunya
viruses.(See'Mosquitoprotection'below.)
ZikavirusRNAhasbeendetectedinblood,urine,semen,saliva,cerebrospinalfluid,amnioticfluid,andbreast
milk[40,54,5863].Zikavirusisdetectableinthebloodofaninfectedpersonforafewdaystoaweek.However,
ZikavirusRNAhasbeendetectedinpregnancyaslongas10weeksaftersymptomonset[64].Duringthe
outbreakinFrenchPolynesia,3percentofdonatedbloodsamplestestedpositiveforZikavirusbypolymerase
chainreaction[40].
ZikavirusRNAmaybedetectableinurinelongerthaninserum[59,62].Ithasbeendetectedinsemen62days
afteronsetoffebrileillness,whenitwasnolongerdetectableinblood[41].
Issuesrelatedtomaternalfetaltransmissionandbreastfeedingarediscussedseparately.(See"Zikavirus
infection:Evaluationofpregnantwomenandinfants",sectionon'Congenitalinfection'.)
CLINICALMANIFESTATIONSTheincubationperiodbetweenmosquitobiteandonsetofclinical
manifestationsistypically2to14days.Theillnessisusuallymildsymptomsresolvewithintwotosevendays.
Immunitytoreinfectionoccursfollowingprimaryinfection[65].Severediseaserequiringhospitalizationis
uncommon,andcasefatalityratesarelow[6668].
Symptomsandsigns
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AdultsSymptomsandsignsofZikavirusinfectiontypicallyincludeacuteonsetoflowgradefever(37.8to
38.5C),maculopapularpruriticrash,arthralgia(notablythesmalljointsofhandsandfeet),andconjunctivitis
(nonpurulent)clinicalillnessisconsistentwithZikavirusdiseaseiftwoormoreofthesesymptomsarepresent
[16,6971].Othercommonlyreportedclinicalmanifestationsincludemyalgia,headache,retroorbitalpain,and
asthenia[66].Lesscommonlyobservedsymptomsandsignsincludeabdominalpain,nausea,diarrhea,mucus
membraneulcerations[72].Thrombocytopeniahasbeendescribedincasereports[73,74].
ClinicalmanifestationsofZikavirusinfectionoccurin20to25percentofindividualswhobecomeinfectedwith
Zikavirus.Outsideareaswithmosquitotransmission,thelikelihoodofZikavirusinfectionamongasymptomatic
individualsislow[75].
ChildrenTherangeofZikavirusinfectioninchildrenincludesintrauterineinfection(verticaltransmission
duringpregnancy),intrapartuminfection(verticaltransmissionatthetimeofdelivery),andpostnatalinfection
(transmissionviamosquitobites).Issuesrelatedtointrauterineandintrapartuminfectionarediscussedseparately.
(See"Zikavirusinfection:Evaluationofpregnantwomenandinfants".)
Clinicalmanifestationsininfantsandchildrenwithpostnatalinfectionaresimilartothefindingsseeninadultswith
Zikavirusinfection[24,76].Arthralgiaisdifficulttodetectininfantsandyoungchildrenandmaymanifestas
irritability,walkingwithalimp,difficultymovingorrefusingtomoveanextremity,painonpalpation,orpainwith
activeorpassivemovementoftheaffectedjoint[76].Thusfar,nodevelopmentalcomplicationshavebeen
observedinotherwisehealthychildrenwithpostnatalZikavirusinfection[77,78].(See"Evaluationofthechildwith
jointpainorswelling".)
ComplicationsZikavirusinfectionhasbeenassociatedwithcomplicationsincludingcongenitalmicrocephaly
andfetallossesamongwomeninfectedduringpregnancy,aswellasneurologiccomplications.Issuesrelatedto
congenitalinfectionarediscussedseparately.(See"Zikavirusinfection:Evaluationofpregnantwomenand
infants".)
GuillainBarrsyndromeSeveralcountriesintheAmericashavereportedunusualincreasesincasesof
GuillainBarrsyndrome(GBS)inparallelwiththeongoingZikavirusoutbreak[79,80].Anincreaseintherateof
GBSinassociationwithZikavirusinfectionhasalsobeenobservedinotherreports[58,8185].
AcasecontrolstudyinFrenchPolynesiaevaluatedtheassociationbetweenGBSandZikavirusinfectionduring
the2013to2014outbreak[85].Casesincluded42patientsdiagnosedwithGBSonecontrolgroupincluded98
patientswithnonfebrileillnesses(matchedforage,sex,andresidence),andasecondcontrolgroupincluded70
patientswithZikavirusinfectionintheabsenceofneurologicalcomplications.Zikaimmunoglobulin(Ig)Mwas
positivein93percentofGBScases(versus17percentofpatientsinthefirstcontrolgroup)serologicevidenceof
pastdengueinfectionwassimilaramongallthreegroups.AntiglycolipidIgGantibodiesweredetectedinfewer
than50percentofGBScases,raisingthepossibilityofdirectviralneurotoxicity.Resultsofnerveconduction
studieswereconsistentwiththeacutemotoraxonalneuropathytypeofGBSclinicalimprovementduringfollow
upsuggestedreversibleconductionfailure.SymptomsofZikavirusinfectionoccurredin88percentofpatients
withGBSthemedianintervalbetweenviralsyndromeandonsetofneurologicalsymptomswassixdays.AllGBS
casesreceivedintravenousimmuneglobulin,38percentrequiredintensivecare,and29percentneededrespiratory
careallsurvived.TheincidenceofGBSduringtheoutbreakwasestimatedtobe2.4casesper10,000Zikavirus
infections.
Issuesrelatedtodiagnosis,evaluation,andmanagementofGuillainBarrsyndromearediscussedfurther
separately.(See"ClinicalfeaturesanddiagnosisofGuillainBarrsyndromeinadults"and"Treatmentand
prognosisofGuillainBarrsyndromeinadults".)
OtherneurologiccomplicationsZikavirushasbeenassociatedwithotherneurologiccomplications
includingbrainischemia[68],myelitis[86],andmeningoencephalitis[87].Theseentitiesarediscussedfurther
separately.(See"Transversemyelitis"and"Viralencephalitisinadults".)

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DIFFERENTIALDIAGNOSISThedifferentialdiagnosisofZikavirusinfectionincludes:
Otherviralcausesofarthritis:
DenguefeverDenguevirusandZikavirusinfectionshavesimilarclinicalmanifestationsandare
transmittedbythesamemosquitovector.However,dengueinfectionusuallypresentswithhighfever,
severemusclepain,andheadacheandmayalsobeassociatedwithhemorrhageunlikeZikainfection,
dengueistypicallynotassociatedwithconjunctivitis(table1).CoinfectionwithZika,chikungunya,and
dengueviruseshasbeendescribed[88].Thediagnosisofdenguevirusinfectionisestablishedvia
serology.(See"Clinicalmanifestationsanddiagnosisofdenguevirusinfection".)
ChikungunyaChikungunyavirusandZikaviruscausesimilarsymptomsandsignsandare
transmittedbythesamemosquitovector.However,chikungunyausuallypresentswithhighfeverand
intensejointpainaffectingthehands,feet,knees,andbackunlikeZikainfection,chikungunyais
typicallynotassociatedwithconjunctivitis(table1).Chikungunyainfectioncanbedisabling,causing
patientstobendoversuchthattheycannotwalk,andinfectedindividualsmaybeunabletoperform
simplemanualtasks.CoinfectionwithZika,chikungunya,anddengueviruseshasbeendescribed[88].
Thediagnosisofchikungunyavirusinfectionisestablishedviaserology.(See"Chikungunyafever".)
ParvovirusParvovirusinfectioncanpresentwithacuteandsymmetricarthritisorarthralgia,most
frequentlyinvolvingthesmalljointsofthehands,wrists,knees,andfeet.Rashmayormaynotbe
present.Thediagnosisisestablishedviaserology.(See"Clinicalmanifestationsanddiagnosisof
parvovirusB19infection".)
RubellaClinicalmanifestationsofrubellaincludelowgradefeverandcoryza.Macularrashbeginson
thefaceandspreadstothetrunk,andarthritisandlymphadenopathymaybepresent.Thediagnosisis
establishedviaserology.(See"Rubella".)
Anumberofothervirusesincludingenterovirus,adenovirus,andalphavirusesmayalsocausearthritis
thesearediscussedfurtherseparately.(See"Specificvirusesthatcausearthritis".)
MeaslesClinicalmanifestationsofmeaslesincludefever,cough,sorethroat,coryza,conjunctivitis,and
lymphadenitis.Koplikspotsmayprecedethegeneralizedrash.Thediagnosisisestablishedviaserology.
(See"Clinicalmanifestationsanddiagnosisofmeasles".)
LeptospirosisLeptospirosisischaracterizedbyfever,rigors,myalgia,conjunctivalsuffusion,and
headache.Lesscommonsymptomsandsignsincludecough,nausea,vomiting,diarrhea,abdominalpain,
andarthralgia.ItmaybedistinguishedfromZikavirusinfectionbythepresenceofjaundice.Thediagnosisis
establishedviaserology.(See"Epidemiology,microbiology,clinicalmanifestations,anddiagnosisof
leptospirosis".)
MalariaMalariaischaracterizedbyfever,malaise,nausea,vomiting,abdominalpain,diarrhea,myalgia,
andanemia.Thediagnosisofmalariaisestablishedbyvisualizationofparasitesonperipheralsmear.(See
"Clinicalmanifestationsofmalariainnonpregnantadultsandchildren".)
RickettsialinfectionRickettsialinfectionswithsimilarmanifestationsasZikavirusinfectionincludeAfrican
tickbitefeverandrelapsingfever.AfricantickbitefeverisobservedamongtravelerstoAfricaandthe
Caribbeanandischaracterizedbyheadache,fever,myalgia,solitaryormultipleescharswithregional
lymphadenopathy,andgeneralizedrashthediagnosisisestablishedviaserology.Relapsingfeveris
characterizedbyfever,headache,neckstiffness,arthralgia,myalgia,andnauseadiagnostictoolsinclude
directsmearandpolymerasechainreaction.(See"Otherspottedfevergrouprickettsialinfections"and
"Clinicalfeatures,diagnosis,andmanagementofrelapsingfever".)
GroupAStreptococcusClinicalmanifestationsofgroupAStreptococcusinfectionincludefever,myalgia,
cutaneousmanifestations(cellulitis,fascitis),pharyngitis,andshock.Thediagnosisestablishedbypositive
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culturesfromthebloodorothertissues.(See"GroupAstreptococcal(Streptococcuspyogenes)bacteremia
inadults".)
DIAGNOSISTheapproachtoZikavirusdiagnosismayvarydependingonavailableresourcestheapproach
outlinedinthefollowingsectionsmayneedtobetailoredtolocalcircumstances.
ThediagnosisofZikavirusinfectionshouldbesuspectedinindividualswithtypicalclinicalmanifestationsand
relevantepidemiologicexposure(residenceinortraveltoanareawheremosquitobornetransmissionofZikavirus
infectionhasbeenreported,orunprotectedsexualcontactwithapersonwhomeetsthesecriteria).
IssuesrelatedtodiagnosisofZikavirusinfectioninnonpregnantadultsandchildrenwithpostnatalinfectionare
reviewedbelow.Issuesrelatedtodiagnosisofmaternal,intrauterine,andintrapartuminfectionarediscussed
separately.(See"Zikavirusinfection:Evaluationofpregnantwomenandinfants".)
CasedefinitionsThefollowinginterimcasedefinitionshavebeenissuedbytheWorldHealthOrganization
(WHO)toprovideglobalstandardizationforclassificationandreportingofZikaviruscases[89].
Asuspectedcaseisapersonwitharash(maculopapular)and/orfever(37.8to38.5C)withatleastoneof
thefollowingsymptoms(notexplainedbyothermedicalconditions):arthralgia,arthritis,orconjunctivitis
(nonpurulent/hyperemic).Asuspectedcaseshouldalsohaverelevantepidemiologicexposure(residencein
ortraveltoanareawheremosquitobornetransmissionofZikavirusinfectionhasbeenreported,or
unprotectedsexualcontactwithapersonwhomeetsthesecriteria),eventhoughepidemiologicexposureis
notincludedintheWHOcategorizationofasuspectedcase.
Aprobablecaseisasuspectedcasewithimmunoglobulin(Ig)MantibodyagainstZikavirus(withno
evidenceofinfectionwithotherflaviviruses)andrelevantepidemiologicexposure(asdescribedabove).
AconfirmedcaseisapersonwithlaboratoryconfirmationofZikavirusinfection,eitherbydetectionofviral
RNAorantigeninserumorothersamplesorbydetectionofZikaIgMantibodyandZikavirus90percent
plaquereductionneutralizationtest(PRNT90)titer20andPRNT90titerratio4comparedwithother
flaviviruses.
Fornonpregnantpatientsresidinginareaswheremosquitotransmissionhasbeenestablished,thediagnosisof
Zikavirusinfectionmaybesuggestedbasedonsymptomsandsignsandmaynotnecessarilywarrantlaboratory
testing,althoughdifferentiationfromotherillnesseswithsimilarclinicalmanifestations(eg,dengue,chikungunya)
maybedifficult[90,91].
Fornonpregnantpatientsresidinginareaswheremosquitotransmissionhasnotbeenestablishedandlaboratory
testingisavailable,diagnostictestingiswarrantedforindividualswithcharacteristicsymptomsandsignsand
relevantepidemiologicexposure.(See'Nonpregnantadults'below.)
Theapproachtodiagnosticevaluationofpregnantwomenandinfantswithintrauterineorintrapartuminfectionis
discussedseparately.(See"Zikavirusinfection:Evaluationofpregnantwomenandinfants".)
NonpregnantadultsThediagnosisofZikavirusinfectionisdefinitivelyestablishedviareversetranscription
polymerasechainreaction(RTPCR)forZikaviralRNAorZikavirusserology[16,69,9294]:
Forindividualswithinthefirstsevendaysafteronsetofsymptoms,thediagnosisofZikavirusinfectionmay
beestablishedviaRTPCRofserumfordetectionofZikavirusRNA.RTPCRispositiveonlyforabrief
window(threetosevendays)whentheinfectedpersonhasviremiatherefore,negativeresultscannot
excludeinfection.RTPCRtestingfordenguevirusandchikungunyavirusshouldalsobepursued.
Forindividualsfourormoredaysaftertheonsetofsymptoms,thediagnosisofZikavirusinfectionmaybe
establishedbyZikavirusserologictesting(ZikavirusIgMandneutralizingantibodytitersthatare4fold
higherthandenguevirusneutralizingantibodytitersinserum).Measuringvirusspecificneutralizing
antibodiesisusefulfordiscriminatingbetweencrossreactingantibodiesfromotherflavivirusinfections
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testingisconsideredinconclusiveifZikavirusneutralizingantibodytitersare<4foldhigherthandengue
virusneutralizingantibodytiters.Acuteandconvalescentserashouldbeobtainedtodetectanincreased
antibodytiterinpairedsampleswithanintervaloftwotothreeweeks.
Serologictestingfordenguevirusinfectionandchikungunyavirusinfectionshouldalsobepursued.Asingle
laboratoryPCRtestisavailablethroughtheUnitedStatesCentersforDiseaseControlandPrevention
(CDC)andotherqualifiedlaboratoriestoevaluateforpresenceofZika,chikungunya,ordengueinfection
[95].Allserologicresultsshouldbeinterpretedwithcautionsincetherecanbecrossreactivitywithother
flaviviruses(includingdenguevirusandWestNilevirus).Crossreactivitymayalsobeobservedin
individualswhohavebeenvaccinatedagainstyellowfeverorJapaneseencephalitis[96].Issuesrelatedto
diagnosisofdenguevirusandchikungunyavirusarediscussedseparately.(See"Clinicalmanifestationsand
diagnosisofdenguevirusinfection"and"Chikungunyafever",sectionon'Diagnosis'.)
ForindividualspresentingfourtosevendaysafteronsetofsymptomswithnegativeZikavirusRTPCR,
Zikavirusserologictesting(ZikavirusIgMandneutralizingantibodytiters)shouldbeperformed.
LaboratorytestingforZikavirusinfectionisnotcommerciallyavailabletestingisperformedbythePanAmerican
HealthOrganization/WHO,theCDCArboviralDiagnosticLaboratory,andsomestatehealthdepartments.
IntheUnitedStates,statehealthdepartmentsshouldbecontactedtofacilitatediagnostictestingforZikavirus
infection.LaboratoryspecimensmayalsobesenttotheCDCArboviralDiagnosticLaboratoryinstructionsare
availableonline.Communicationshouldbeinitiatedwiththelaboratoryviatelephone(19702216400)priorto
shipmentofspecimens.
ChildrenwithpostnatalinfectionPostnatalZikavirusinfection(eg,transmittedviamosquitobites)shouldbe
suspectedinaninfantorchild<18yearswithrelevantepidemiologicexposureinthelasttwoweeksand2ofthe
followingmanifestations:fever,rash,conjunctivitis,orarthralgia[76].(See'Children'above.)
Thediagnosticapproachforthesechildrenisthesameasforadults,asdescribedabove.(See'Nonpregnant
adults'above.)
MANAGEMENTThereisnospecifictreatmentforZikavirusinfection.Managementconsistsofrestand
symptomatictreatment,includingdrinkingfluidstopreventdehydrationandadministrationofacetaminophento
relievefeverandpain[97].
Aspirinandothernonsteroidalantiinflammatorydrugs(NSAIDS)shouldbeavoideduntildengueinfectionhas
beenruledout,toreducetheriskofhemorrhage.Aspirinshouldnotbeusedinchildrenwithacuteviralillness
becauseofitsassociationwithReyesyndrome.(See"Acutetoxicmetabolicencephalopathyinchildren",section
on'Reyesyndrome'.)
TheWorldHealthOrganizationhasissuedinitialguidanceonpsychosocialsupportforpatientsandfamilies
affectedbyZikavirusinfectionandassociatedcomplications[98].
PREVENTIONThereisnovaccineforpreventionofZikavirusinfection.Modesoftransmissionaredescribed
above.(See'Transmission'above.)
Preventivemeasuresforpregnantandlactatingwomenandwomenofchildbearingpotentialarediscussed
separately.(See"Zikavirusinfection:Evaluationofpregnantwomenandinfants",sectionon'Prevention'.)
MosquitoprotectionIndividualsinareaswithriskfortransmissionshouldtakemeasurestoavoidmosquito
bites,includingpersonalprotectionaswellasenvironmentalcontrolmeasures[58].Aedesmosquitoesbiteduring
thedaytimeaswellasattwilighttheybreedinstandingwater(particularlymanmadecontainers)[99].
Personalprotectivemeasuresinclude[58]:
Preventingmosquitobitesbywearinglongsleevesandlongpants,usinginsectrepellent,andstaying
indoorsasfeasible(withairconditioning,window/doorscreens,and/ormosquitonetstominimizecontact
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betweenmosquitoesandpeople).(See"Preventionofarthropodandinsectbites:Repellentsandother
measures".)
IndividualswithZikavirusinfectionmayreducespreadofinfectiontoothersbyfollowingthesame
precautionstoavoidmosquitobitesduringthefirstweekofillness.
Environmentalcontrolmeasuresincludeidentificationandeliminationofpotentialmosquitobreedingsites.
Mosquitolarvaebreedinstandingwatertherefore,residentsshouldbeinstructedtoavoidallowingstandingwater
tocollectoutdoors(suchasinflowerpots,buckets,bottles,jars,andothersimilarcontainersnearhouses).
Domesticwatertanksshouldbecoveredsothatmosquitoescannotenter,anddrainsthatallowstagnantor
standingwatershouldbeeliminated.Localanddistricthealthdepartmentscanhelpfacilitatemitigationof
transmissionrisk.(See"Malariainendemicareas:Epidemiology,prevention,andcontrol",sectionon'Mosquito
vectorcontrol'.)
SexualtransmissionItisprudentforindividualswithZikavirusinfection/exposuretoabstainfromsexual
activity(vaginal,anal,andoralsex)orusebarrierprotection(ideallycondoms)whileactivemosquitotransmission
persists[100].Menwhohaveapregnantpartnershouldabstainfromunprotectedsexforthedurationofthe
pregnancy[44,45,101105].
OutsideareasofZikavirusmosquitotransmission,ithasbeensuggestedthatmenwithsymptomaticZikavirus
infection(confirmedorsuspected)waitatleastsixmonthsbeforehavingunprotectedsexandthatasymptomatic
menwithZikavirusexposure(viatraveltomosquitotransmissionareasorsexualcontact)waitatleasteight
weeksbeforeunprotectedsex[101,105].(See"Malecondoms",sectionon'Instructionsforuse'.)
Thedurationofviralpersistenceinsemenisnotknown.OnereportdescribeddetectionofZikavirusRNAby
reversetranscriptionpolymerasechainreactioninsemen62daysafteronsetoffebrileillness,whenitwasno
longerdetectableinblood[41].Theinfectiousviralloadinsemenmaybehighinonereport,theviralloadin
semenmorethantwoweeksafteronsetofsymptomswasroughly100,000timesthatofbloodorurine[106].
Blood/tissuedonationZikavirusistransmissibleviabloodproductsandorganortissuetransplantation
[40,48].Issuesrelatedtodonorscreeningarediscussedfurtherseparately.(See"Blooddonorscreening:Medical
history",sectionon'Zikavirus'and"Blooddonorscreening:Laboratorytesting".)
TheUSFoodandDrugAdministration(FDA)hasissueddonordeferralrecommendationsforhematopoieticstem
cells,tissues,anddonorgametestherecommendationsdonotapplytosolidorgans[107].Livingdonorswith
Zikavirusinfectionorrelevantepidemiologicexposure(residenceinortraveltoanareawheremosquitoborne
transmissionofZikavirusinfectionhasbeenreported,orunprotectedsexualcontactwithapersonwhomeets
thesecriteria)shouldbeconsideredineligiblefordonationforsixmonths.DeceaseddonorswithZikavirus
infectionintheprecedingsixmonthsshouldbealsobeconsideredineligible.
NosocomialtransmissionTransmissionofZikavirusviaoccupationalexposureinahealthcaresettinghas
notbeendescribed.Standardprecautionsareappropriateforprotectionofhealthcarepersonnelandpatientsfrom
Zikavirusinfectioninthesesettings[108].(See"Generalprinciplesofinfectioncontrol",sectionon'Standard
precautions'.)
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and
"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortable
withsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
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"patientinfo"andthekeyword(s)ofinterest.)
Basicstopic(see"Patientinformation:Zikavirusinfection(TheBasics)")
SUMMARY
OutbreaksofZikavirusinfection,causedbyanemergingmosquitoborneflavivirus,haveoccurredinAfrica,
SoutheastAsia,andthePacificIslandscurrently,thereisanongoingZikavirusoutbreakintheAmericas.
ZikavirusistransmittedtohumansviathebiteofaninfectedAedesmosquito.Thistypeofmosquitousually
bitesduringthedaytimeandbreedsinstandingwater(particularlymanmadecontainers).(See'Epidemiology'
above.)
ClinicalmanifestationsofZikavirusinfectionincludeacuteonsetoflowgradefeverwithmaculopapular
pruriticrash,arthralgia(notablysmalljointsofhandsandfeet),orconjunctivitis(nonpurulent)clinicalillness
isconsistentwithZikavirusdiseaseiftwoormoreofthesesymptomsarepresent.Zikavirusinfectionhas
alsobeenassociatedwithcongenitalmicrocephaly,fetalloss,andGuillainBarrsyndrome.(See'Clinical
manifestations'above.)
Theincubationperiodbetweenmosquitobiteandonsetofclinicalmanifestationsistypically2to14days.
Theillnessisusuallymildclinicalmanifestationsusuallyresolvewithintwotosevendays.Asymptomatic
infectioniscommonsymptomsdevelopin20to25percentofindividualswhobecomeinfectedwithZika
virus.Onceapersonhasbeeninfected,heorsheislikelytobeprotectedfromfutureinfections.(See
'Symptomsandsigns'above.)
ThediagnosisofZikavirusinfectionshouldbesuspectedinindividualswithtypicalclinicalmanifestations
andrelevantepidemiologicexposure(residenceinortraveltoanareawheremosquitobornetransmissionof
Zikavirusinfectionhasbeenreported,orunprotectedsexualcontactwithapersonwhomeetsthese
criteria).(See'Diagnosis'above.)
ThediagnosisofZikavirusinfectionisestablishedviaserumreversetranscriptionpolymerasechainreaction
(RTPCR)testingorserology.Withinthefirstsevendaysfollowingonsetofsymptoms,thediagnosismay
beestablishedviaserumRTPCRfordetectionofZikaviralRNA.Fourormoredaysaftertheonsetof
symptoms,thediagnosismaybeestablishedviaZikavirusserologictesting.(See'Nonpregnantadults'
above.)
ThereisnospecifictreatmentforZikavirusinfectionandthereisnovaccineforprevention.Management
consistsofsymptomatictreatment.Preventivemeasuresincludepersonalprotectivemeasurestoprevent
mosquitobitesandinstitutionofmeasurestoeliminateandcontrolmosquitobreedingsites.(See
'Management'aboveand'Mosquitoprotection'above.)
SexualtransmissionofZikavirushasbeendescribed.ItisprudentforindividualswithZikavirus
infection/exposuretoabstainfromsexualactivity(vaginal,anal,andoralsex)orusebarrierprotection
(ideallycondoms)whileactivemosquitotransmissionpersistsmenwhohaveapregnantpartnershould
followsuchguidanceforthedurationofthepregnancy.OutsideareasofZikavirusmosquitotransmission,it
hasbeensuggestedthatmenwithsymptomaticZikavirusinfection(confirmedorsuspected)waitatleast
sixmonthsbeforehavingunprotectedsexandthatasymptomaticmenwithZikavirusexposure(viatravelto
mosquitotransmissionareasorsexualcontact)waitatleasteightweeksbeforeunprotectedsex.(See
'Sexualtransmission'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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Topic106169Version64.0

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GRAPHICS
EstimatedrangeofAedesaegyptiandAedesalbopictusinthe
UnitedStates

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Thesemapsshowareaswheremosquitoesareorhavebeenpreviouslyfound(basedona
varietyofsources)andreflectestimatesofthepotentialrangeofAedesaegyptiandAedes
albopictusintheUnitedStates.Thesemapsdonotshowexactlocationsornumbersof
mosquitoeslivinginanareanordotheyrepresentriskforspreadofdisease.
Reproducedfrom:CentersforDiseaseControlandPrevention.ZikaVirus:VectorSurveillanceand
Control.Availableat:http://www.cdc.gov/zika/vector/index.html(AccessedonMarch31,2016).
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GlobaldistributionofAedesaegyptiandAedesalbopictus

From:MussoD,GublerDJ.Zikavirus.ClinMicrobiolRev201629(3):487524.DOI:10.1128/CMR.0007215.Repro
permissionfromAmericanSocietyforMicrobiology.Copyright2016.
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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).
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ContributorDisclosures
A.DesireeLaBeaud,MD,MSNothingtodisclose.MartinSHirsch,MDNothingtodisclose.ElinorLBaron,
MD,DTMHNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovided
tosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDate
standardsofevidence.
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