ThePoten)alIntroduc)onofZikavirusintotheUS–Implica)onsforPublicHealthandBloodSafety–

LessonsLearnedfromOtherArboviruses

SusanL.Stramer,PhDVP,Scien)ficAffairs

ThrombosisandHemostasisSocie)esofNorthAmerica

2016Summit,April15

1

NothingtoDisclose

CurrentArboviralThreatstotheCon)nentalUS

• Dengue:1/3ofworldpopula8onatrisk,30-foldincreasein50yrs• Chikungunya:Re-emergedintheAmericaslate2013;≈1.7Mcases• Zika:evidenceofpastorcurrenttransmissionacrossAfrica,Asia,W.Pacific;confirmedinBrazilMay2015;nowass’dwithmicrocephalyandGuillain-Barrésyndrome;62countriestotalsince2007;33countriesintheAmericasto2016

Dengueriskmaps

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DengueIncidenceisRapidlyIncreasingintheAmericas

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27,084suspectedcases

FrenchWestIndes1Dec2013–24Apr2015Guadeloupe:81,350cases

PuertoRico

Mar)nique:72,520cases

PuertoRico:31,433cases

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PuertoRico,PassiveDengueSurveillanceSystem

199917

Oct28,

SpreadofZIKAVirus(ZIKV)

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SpreadoftheZIKV•  1947:firstdetectedinUganda,Africa

•  1947to2007:14humaninfec)onswerereported(AfricaandAsia)

•  2007:FirstoutbreakinYap,FederatedStatesofMicronesia,Pacific

•  2007to2013:1infec)oninPhilippinesfromretrospec)vestudy

•  2013to2014:AlargeoutbreakoccurredinFrenchPolynesiawith ~32,000symptoma)ccases,11%ofthepopula)on

2.8%rateofRNAinblooddonors,11/42(26%)reportedPDI,viralloads10^3-10^7copies/mL

•  2014:SpreadthroughouttheSouthPacific

•  2015:SpreadtoSouthAmerica(BrazilandColumbia)

Jones KE, Patel NG, Levy MA. et al. Nature 2008 12

ZIKVpublica)ons:1952-2009(firstdescrip8ontofirstoutbreakinYap)=252010-2015632016225

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Petersenetal.,ZikaVirus;NEJMMarch30,2016

Endemic

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ZIKVVectors:AedesMosquitoes

•  Aedes(stegomyia)speciesmosquitoes–  Ae.aegyp.mostefficientvectorforhumans

–  Ae.albopictusspreadinmoretemperatezones

•  Alsotransmitdengueandchikungunyaviruses

•  Layeggsindomes8cwater-holdingcontainers;toleratedrying

•  Liveinandaroundhouseholds•  Aggressiveday8mebiters;canalsobiteatnight

•  Mul8plehumansbibenforasinglebloodmeal

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ArbovirusComparisonCharacteris)c Dengue Chikungunya Zika

Virusfamily Flaviviridae Togaviridae Flaviviridae

Virusgenus Flavivirus Alphavirus Flavivirus

Serotypes 4 1 1

Genotypes Mul)pleperserotype 3 2

Vectors Aedesaegyp*Aedesalbopictus

Aedesaegyp*Aedesalbopictus

Aedesaegyp*Aedesalbopictus

Symptoms/illness

Acutefebrileillness

Acutefebrileillness

Acutefebrileillness

Symptoma)c:Asymptoma)c 25:75 75:25 25:75

Illnessoutcome Severedengue–plasmaleakage

Rarelysevere,Arthralgias

Rarelysevere,Microcephaly,Guillian-Barré 16

ZIKV(forAABBFactSheetPriorto2013)

•  Mosquito-borneviraldisease•  Zikarecognizedin1947intheZikaforestinUgandaintherhesus

macaques;AfricanlineageandAsianlineage•  Usuallymild,las8ngfor2-7days•  Mainsymptomsinclude:

–  Low-gradefever(<38.5°C)–  Transientarthri8s/arthralgiawithpossiblejointswellingmainlyinthe

smallerjointsofthehandsandfeet•  Maculopapularrashojenspreadingfromthefacetothebody•  Conjunc8valhyperemiaorbilateralnon-purulentconjunc8vi8s•  Generalnon-specificsymptomssuchasmyalgia,astheniaandheadaches•  Incuba8onperiod3-12days•  Infec8onmaygounrecognizedorbemisdiagnosedasdengue,

chikungunyaorotherviralinfec8onsgivingfeverandrash.Asymptoma8cinfec8onsaretherule,≈75%

•  Diseaseisusuallymild 17

ClinicalFeatures:ZIKVComparedtoDengue(DENV)andChikungunya(CHIKV)

Features ZIKV DENV CHIKV

Fever + +++ +++Rash +++ + ++Conjunc)vi)s ++ - -Arthralgia ++ + +++Myalgia + ++ +Headache + ++ ++Hemorrhage - ++ -Shock - + -

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ZIKVandGuillain-BarréSyndrome,2013-2014•  ZIKVinfec8onhistoricallywasthoughttoproduceamilddisease•  WiththelargeoutbreakinFrenchPolynesia(~32,000cases),ariseincasesof

Guillian-BarréSyndromewasobserved•  Pastincidencewasabout5casesperyear•  DuringtheZIKVoutbreak,42casesin6months(20Xincrease)

•  AllhadZIKVneutralizingan8body•  15admibedtointensivecareunits•  FrenchPolynesiaonlyhas270,000inhabitants!

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ZikaandGuillain-BarréSyndrome

OR>34betweenGBSandpriorZIKVinfec8onNow13countries/territoriesreportanincreaseinGBS

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ZIKVGenomefromtheAmericasAsiangenotypemostcloselyrelatedtotheFrenchPolynesian2013strainPa8entwithExanthemaandconjunc8vi8s

Enfissietal.Jan62016TheLancet

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ZIKV-AssociatedMicrocephalytoDec2015

•  Ane8ologicroleforZIKVhasnotbeenproven,but…..•  ZIKVRNAhasbeenisolatedfromatleast3casesinBrazil,2fromamnio8cfluidoffetuseswithmicrocephalyonultrasoundandonefrombloodand8ssueofababythatdiedatbirth

•  4mothersofmalformedbabiesinFrenchPolynesiahavebeenfoundtohaveIgGan8-ZIKV,buthavenohistoryofcompa8bleillness

•  Es8matedrisk1:100infirsttrimester•  Diagnos8ctes8ngrequiredtodifferen8ateDENV,CHIKVandZIKV–  Note:othercausesincludeinfec8ons(toxo,rubella,herpes,syphilis,CMV,HIV),toxins,alcohol,gene8cabnormali8esandseveremalnutri8onduringpregnancy 22

ZIKADiseaseinBrazil(Dec82015)1,761reportedin422municipali)esin14Brazilianstateswith19fatali)es

1.PossibleZIKVinfec8onduringpregnancy.2.FetalCNSchangeswithpossiblyrelatedZIKVinfec8onduringpregnancy.3.Miscarriageduetopossibleassocia8onwithZIKVinfec8onduringpregnancy.4.S8llbornduetopossibleinfec8onduringpregnancyZIKV.5.Newbornlivewithmicrocephalypossiblyassociatedwithinfec8onZIKVduringpregnancy.

ProtocolfromtheSecretaryofHealthSurveillanceremonitoringforZIKV-associatedmicrocephalyandfetalmalforma)ons:

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RatesofMicrocephalyOverTime:theAmericasandtheCaribbean

20-foldincreaseinratesofmicrocephalyintheAmericasandCaribbeanfrom2010-2014and2015

Source:PanAmericanHealthOrganiza)on,Epidemiologicalupdate,17January2016

MicrocephalyratesbystateinBrazil(casesper1,000livebirths)

EpiWeek522015

Countrylimits

BrazilStateBoundaries

0.1-1.01.1-15.015.1-30.030.1-45.0

45.1-88.6

Countries

CountrieswithZikaconfirmedcases

UpdatedasofEpidemiologicalWeek52(December27,2015–January2,2016)

DataSource:ReportedfromtheIHRNa8onalFocalPointsandthroughtheMinistryofHealthwebsites.

MapProduc)on:PAHO-WHOADCHAIRARO

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ZIKVinBrazil•  Es8matednumberofinfec8ons–  498,000to1,482,000

•  27/27stateshavereportedcasesofmicrocephaly

•  2982reportedcasesin2015•  2908reportedcasesin2016(thruMarch27)–  Previously147-175(2010-2014)

•  907confirmedplus4293underinves8ga8on

•  46confirmeddeaths–  130underinves8ga8on

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Feb102016

PregnantfemalereturnsfromRioGrandedoNortestate;weeks20-28normalpregnancyDuring13thweek,shehadhighfever,musculoskeletalandretroorbitalpain,itchingandrashAbnormali8esatweek32=>pregnancyterminated

intrauterinegrowthretarda8on,microcephaly,brainstructuresblurred,extremelycalcified(includingtheplacenta),severebraindiseasenoothercausesofmicrocephaly(family)

ZIKVRNAbyRT-PCR6.5x10^7copies/mgbrain8ssue;allotherflavivirusesandothervirusesnegFullgenomesequencedfromthefetalbrain;densepar8clesresemblingvirusand

envelopedstructuresresemblingreplica8vecomplexesalsoobserved99.7%gene8crelatednesstoFrenchPolynesia2013strainandSaoPaulo2015strainNopresenceofZIKVandnopathologicalfindingsdetectedinanyotherfetalorgans=>Strongneurotropismofthevirus

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ZikavirusintheAmericas:Earlyepidemiologicalandgene)cfindings–

Casesappeared2yearsa=eritsintroduc*onintoBrazil

by Nuno Rodrigues Faria, Raimunda do Socorro da Silva Azevedo, Moritz U. G. Kraemer, Renato Souza, Mariana Sequetin Cunha, Sarah C. Hill, Julien Thézé,

Michael B. Bonsall, Thomas A. Bowden, Ilona Rissanen, Iray Maria Rocco, Juliana Silva Nogueira, Adriana Yurika Maeda, Fernanda Giseli da Silva Vasami, Fernando Luiz de Lima Macedo, Akemi Suzuki, Sueli Guerreiro Rodrigues, Ana Cecilia Ribeiro

Cruz, Bruno Tardeli Nunes, Daniele Barbosa de Almeida Medeiros, Daniela Sueli Guerreiro Rodrigues, Alice Louize Nunes Queiroz, Eliana Vieira Pinto da Silva, Daniele

Freitas Henriques, Elisabeth Salbe Travassos da Rosa, Consuelo Silva de Oliveira, Livia Caricio Martins, Helena Baldez Vasconcelos, Livia Medeiros Neves Casseb,

Darlene de Brito Simith, Jane P. Messina, Leandro Abade, José Lourenço, Luiz Carlos Junior Alcantara, Maricélia Maia de Lima, Marta Giovanetti, Simon I. Hay, Rodrigo Santos de Oliveira, Poliana da Silva Lemos, Layanna Freitas de Oliveira, Clayton Pereira Silva de Lima, Sandro Patroca da Silva, Janaina Mota de Vasconcelos,

Luciano Franco, Jedson Ferreira Cardoso, João Lídio da Silva Gonçalves Vianez-Júnior, Daiana Mir, Gonzalo Bello, Edson Delatorre, Kamran Khan, Marisa Creatore,

Giovanini Evelim Coelho, Wanderson Kleber de Oliveira, Robert Tesh, Oliver G. Pybus, Marcio R. T. Nunes, and Pedro F. C. Vasconcelos

Published by AAAS 28

Fig.1TimeseriesandcartographyofreportedZIKVandmicrocephalycasesinBrazil

Nuno Rodrigues Faria et al. Science 2016;science.aaf5036

Published by AAAS 29

Fig.2MaximumlikelihoodphylogenyofZIKVcompletecodingregionsequences

Nuno Rodrigues Faria et al. Science 2016;science.aaf5036 Published by AAAS 30

Fig.3Timescaleoftheintroduc)onofZIKVtotheAmericas

Nuno Rodrigues Faria et al. Science 2016;science.aaf5036 Published by AAAS 31

OthermodesofZIKVtransmission(otherthanmosquito,intrauterine)•  Sexual

–  2healthcareworkersreturnedfromSenegalin2008(Foyetal.EID2011fromCDC)

•  Sexualtxfromcase1tohiswife(case3)uponreturntoCO•  Sexualintercourse1dayajerhisreturn;3dayslater,case1developedprosta88s,hematospermiaandhiswifedevelopedflu-likeillness;shehadnotravelhistoryorknownmosquitoexposure;semenwasnotinves8gatedforRNAbutbothtestedZIKVseroposi8ve

–  ZIKVRNAisolatedfromsemenandurinepublishedinEID,Feb2015bygroupinTahi8(Mussoetal.)

•  Fever,weaknessdays1-3;arthralgiadays5-7•  Hematospermia2weekslater;ZIKARNAposfromsemen;repeated3dayslaterandconfirmedinsemen(10^7copies/mL)andurine(10^3copies/mL);bloodnega8ve;virusalsocultureposfromsemen

–  ZIKVRNArecoveredfromsemenofapa8entreturningfromtheCookIslandsondays27and62ajersymptomonset(Atkinsonetal.,EID2016)

–  Casesinves8gatedintheUS(6countriesnowrepor8ng)32

Detec)onofZIKVinUrine;Gouriantetal.,EID;Jan2015

Wedescribethekine8csofZikavirus(ZIKV)detec8oninserumandurinesamplesof6pa8ents.Urinesampleswereposi8veforZIKV>10daysajeronsetofdisease,whichwasanotablylongerperiodthanforserumsamples

Triangles=urine;squares=serumDashedlineindicates>2dayintervalbetweensampling 33

ViralRamp-upStudyin3MacaquesinfectedwithZIKV

hbps://zika.labkey.com/project/OConner/begin.view

10^6copies/mL

10^4copies/mL

10^4copies/mL

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Rossietal.,2016

MicelackingIFNreceptorsupportdiseaseandmortalitywhenZIKVchallengedAgedependentresponse(3wo=>deathvs11week=>diseasebutrecovered)Growthinthebrainbyday3withneurologicdiseasebyday6Robustreplica8oninthetestes

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OthermodesofZIKVtransmission•  Transfusion-highviral8tersupto14days

–  2casesfromBrazil(bothCampinas,SaoPauloState)–  FirstMarch2015reportedtoHV

•  3dayspost-dona8on,reportDENV-likesymptomsfromdonor,laterdiagnosedasZIKV=>ZIKVRNApos(negDENV/CHIKV)

•  Platelets=>liverrecipient,remainedasymptoma8cforZIKV,butRNApos(andculturepos;pre-txsampleneg)

•  Sequenceiden8tybetweendonor/recipient–  2ndcaseApril2015

•  Gunshotvic8mrec’d18components=>died•  Recipientunexplainedthrombocytopeniapriortodeath;ZIKVculturepos(negDENV/CHIKV)

•  Reten8onsamplesfrom18componentswerepartofarepositorystudy=>iden8fiedoneZIKVRNAposcomponentreceivedbyrecipient

•  3dayspost-dona8on,donorreportedsymptoms:rash,conjunc8vi8s,severeitching,generalizedpain,hypotension 36

UpdatedZIKVInfo(4/10/16)•  CDCPublicHealthalerts–41areasincluding33intheAmericas,7

islandsintheS.Pacific,and1Africa(CapeVerde)–  Usualmosquitoavoidancemeasures,DEET,longsleeves,pants,sleepunderabednet,removestandingwater

–  Pregnantwomenavoidtravel;condoms,avoidcontactwithsemen

•  Feb1WHOdeclarespublichealthemergencyofinterna8onalconcerntotriggeracoordinatedglobaleffortforeduca8on,surveillance,diagnos8cs,treatment,preven8on(mosquitocontrolandvaccinedevelopment),researchintocongenitalmalforma8onsandneurologicalcomplica8ons–  Only4thinrecentyears:EBOV,Polio,H1N1flu–  Est’d3-4millioncasesintheAmericasinthenext12monthsmodeledajerDENVintheAmericasin2015with~2millioncases(A.aegyp.inthe“dengue-belt”)

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AllCountriesandTerritorieswithAc)veZikaVirusTransmission(4/10/16)

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Considera)onsforBloodSafety

•  Surveillance•  Stopcollec8onsandrelyonimports•  Enhanceddonorsymptomscreening•  Enhancedcallback(PDI)=>Quaran8ne•  14-or28-daytraveldeferralsusedinnonendemicareas

•  Rou8neblooddona8ontes8ng(NAT)•  Pathogeninac8va8on

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Detec)ngZIKVRNAandan)bodies

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Inac)va)onofEmergingPathogens

Pathogen Inac)va)onInPC(Log10)WestNilevirus >6.0

Chikungunyavirus >6.4H1N1virus >4.1H5N1virus >5.9

Dengueviruses >5.0SARS-HCoV >6.3

ParvovirusB19 4=>5.5Orien*atsutsugamushi >5.5Trypanosomacruzi >5.3Babesiamicro* >5.3

Leishmaniamexicana >5.041

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Valida)onofInterceptinac)va)onforZIKVinplasmaunits

Aubryetal.Transfusion2016

FDAGuidance2/16/16•  Areaswithac)veZIKVtransmission;2-weekimplementa8on(March1)orimmediateforpregnantwomen,intrauterinetransfusionorotherriskgroupsasdefinedbythephysician;excep8onsrequirephysicianapprovalifdeemedurgent– ObtainwholebloodandcomponentsfortxfromareasoftheUSwherenoac8vetxisoccurring

–  CanprepareplateletsandplasmausinganFDA-approvedPImethod(ormethodapprovedunderIDE)

–  CantestusingalicensedNAT(ormethodapprovedunderIND)

– DHQmodifiedtoaskaboutadxors/s(cdc.gov)ofZIKVinfec8oninthepast4weeks;historyofsexualcontactinthepast4weekswithamanwhohasbeendxwithorhads/ssugges8veofZIKVinthe3monthspriortothelastsexualcontact 43

FDAGuidance2/16/16•  Areaswithoutac)veZIKAtransmission;4-weekimplementa8on(March15)–  Donoreduca8onalmaterialsallowingdonorstoselfdeferfor4weeks

•  Riskfactorsands/sofZIKVinfec8onwithinthelast2weeksofleavinganac8veZIKVarea(cdc.gov)

•  HistoryofZIKVinfec8onun8l4weeksajerresolu8onofsymptoms•  SexwithamanwhohasbeendxwithZIKVorwhotraveledtoorresidedinanac8veZIKVareainthe3monthspriortothelastsexualcontact

•  Travelnotspecificallymen8oned,butshouldbeincluded(riskfactors)–  DHQmodifiedtoaskaboutresidenceortravelw/inlast4weeks(cdc.gov)

–  PDIasabovewithdonordeferralfor4weeks–  Productquaran8ne/retrievalofindatecomponentsforthosecollectedfromadonoratriskordxduringthe4-weekdeferralperiodorreportedasPDIwithinsubsequent2weeksofcollec8on;consigneeno8fica8onfromadonorwithaZIKVdxwithintheprior4weeksofdona8onor2weeksfollowingdona8on

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ZIKVSigns/Symptoms(2ormore)fromcdc.gov

•  Fever•  Rash•  Jointpain•  Musclepain•  Conjunc8vi8s(redeyes)•  Headache

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Es)mateddonordeferralrate(%)intheUSfroma14-or28-daydeferralbygeographicregion

comparing2surveysAreaoftravelinthepast:

SummerSurvey(Aug-Sept2014)Fixedsitesonly;papersurvey;

AmericasonlyprimarilyN=33,408

WinterSurvey(March2015)Allsites;electronicsurvey;

WorldwideN=19,879

14-day% 28-day% 14-day% 28-day%Mexico 0.19 0.52 0.40 0.92

Caribbean 0.16 0.48 0.48 1.18Centraland

SouthAmerica0.05 0.13 0.20 0.46

Allabove* 0.39 1.17 0.97 2.25Alltravel(global)*

N/A 2.64 1.35 3.96

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*Individualareasandsumsarenotthesameduetoincompleterepor)ngoftraveldes)na)onandtraveltomul)pleplaces.Spenceretal.,AABB2015;Plenary

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AdaptedfromBogochetal.,TheLancetJan142016

ZIKVdiseasecasesreportedtoCDCbyUSstateorterritory—2015–2016

(4/10/16)

LocalTravelContUS0346Territories3513

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SequencingPRNT

EmergencyUseAuthoriza)on:TrioplexReal-)meRT-PCRforDENV,CHIKVandZIKVmul)plexrRT-PCRandZIKVMAC-ELISA(bothCDCassays) 50

*Mapsupdatedfromavarietyofsources;theyrepresentCDC'sbestes8mateofthepoten8alrangeofAedesaegyp.andAedesalbopictusintheUS.Mapsarenotmeanttorepresentriskforspreadofdisease.

ESTIMATEDrangeofAedesaegyp*andAedesalbopictusintheUS,2016Maps

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Thismapes)mateswhichUSci)esfacethehighestriskfromZIKV

hbp://www.sciencealert.com/this-map-es8mates-which-us-ci8es-face-the-highest-risk-from-zika-virus 52

ZikaisComing;NYTimesApril92016;PeterHotezPredictedLoca)onsofAedesaegyp*intheSouthernUS

Factorsfavoringtransmission/spreadofZIKV:Aedesaegyp*,overcrowding,extremepoverty.“Incrowdedplaces,mosquitoeshavelotsofaccesstolotsofpeople.Poorpeopleojenliveinproximitytogarbage,includingold8res,plas8ccontainersanddrainageditchesfilledwithstagnantwater,wherethisspeciesofmosquitolivesandbreeds.Andtheyojenhavehomeswithtornscreensontheirwindows.” 53

Poten)alforlocaltransmissionislikelylow(astakenfromCDPH)

AviremicpersonwouldneedtoreturntoaregionwherethereareAedesmosquitoesandbebibenbyanAedesmosquitothatliveslongenoughtobecomeinfec8ousandbiteanotherperson

Aedestakes10-11daystobecomeinfec8ousajerbecominginfectedandthattheaveragelifespanisonly14daysThus,manyinfectedmosquitoeswilldiebeforebeingabletotransmitMi8ga8ngfactors:PatchyAedesaegyp.andalbopictusdistribu8onUseofaircondi8oners,windowanddoorscreensBeberwatermanagementthaninothercountriesGoodmosquitocontrol!

Ifanoutbreakweretooccur,itwouldlikelybelimitedinscopeanddura8onThefewlocaloutbreaksofDENVandCHIKVintheUShavebeencontainedTherefore,theUSwillprobablynotexperiencethesameextensiveoutbreakscurrentlybeingexperiencedinLa8nAmerica

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DENV CHIKV

Year Local Imported Local Imported

2014 7(FL) 654 12(FL) 2799

2015 1(FL) 540 0 679

ComparisonofUS-reportedcasesofDENVandCHIKVtotheCDC,2014-2015

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ZIKVcasesduetobloodtransfusionhavebeenreported–noneinUSyet!

(astakenfromCDPH)

Upondetec8onoflocalZIKVtransmissioninanystatelocalpublichealthagencieswouldinves8gateandenhancesurveillanceandmosquitocontrolintheareaBloodbankswouldbeinformedoflocaltransmissionsothatdonorsfromthearea(tobedefined)wouldbedeferredfromdona8ngbloodun8lbloodscreeningisinplace

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KeyMessages(astakenfromCDPH)

Riskoflocaltransmissionofchikungunya,dengue,andZikavirusesintheUSislikelylowHowever,transmissionispossibleandwemustbepreparedtoaggressivelyrespondonceacasewithouttravelhistoryhasbeenreported

OngoingsurveillanceandcontrolofAedesarecri8calIndividualswithZika,dengue,orchikungunyashouldbeinformedtotakeprecau8onstoavoidmosquitobitesduringillnesstoavoidini8a8nglocaltransmissionShouldtherebelocaltransmission,theareaofexposureriskwouldbedeterminedbasedonhumanandmosquitosurveillancedataandgeographicboundaries,suchaszipcode,city,orcountywouldbedefinedandreported 57

• Providestateandlocalseniorofficialswithinforma8onandtoolsneededtoimproveZikapreparednessandresponsewithintheirstatesandjurisdic8ons.• IncreaseknowledgeonthelatestZikascience,includingimplica8onsforpregnantwomen.• Increaseknowledgeofbestcommunica8onsprac8ces,includingcrisisandriskcommunica8onprinciples.• AcceleratereadinessforlocalZikatransmissionthroughtrainingandtechnicalassistancetostatestohelpestablishandsupportsurveillanceandsharebestprac8cesforvectorcontrol.• Iden8fypossiblegapsinpreparednessandresponseatthefederal,state,andlocallevels;begintoaddresspossiblegaps. April1,2016 58

Defini)onofareasofac)vevector-bornetransmissionthatwouldac)vatebloodsafetyinterven)on(includingFDAguidance)–DRAFTCONCEPT

Twoormorelaboratory-confirmedinfec8onsduetolocalvector-bornetransmission(e.g.,notravelhistory,nocommonsexualexposure),andepidemiologicallyunrelatedtoeachother(e.g.,notsamehousehold)occurringwithintwoweeksinanaffectedarea Theaffectedjurisdic8onwilldetermine,onthebasisofsurveillance,popula8ondensityandvectorecology,anareaoflikelylocaltransmissionanddefinesuchareaonthebasisofaclusterofZIPcodes.ThisclusterofZIPcodeswillbedefinedastheareaofinterven8onTheclusterofZIPcodeswillbereportedbytheStatetotheCDC 59

Issues•  Bloodsafety

–  Screeningshouldbeinplacepriortoappearanceofvirus=>outbreaks–notthecurrentmodel

•  Mosquitocontrol–  Tradi8onalmethodsineffec8veagainstAedes–  Biologic/gene8cvectorcontrol

•  Infectedorengineeredmosquitoestoyieldsterileoffspring

•  Vaccine–  Timefordevelopment– An8body-dependentenhancement(ADE);wouldpriorflavivirusvaccina8on(YFV)orpriorprimaryinfec8on,orZIKVvaccineexacerbatediseaseinasecondaryinfec8on?

•  Vaccine-inducedGuillain-Barrésyndrome 60

ZIKVcontrolrequiresanurgentandcoordinatedresponse

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