1
Editorial
2
Zika virus outbreak and the case for building effective and sustainable
3
rapid diagnostics laboratory capacity globally
4 Newandre-emergingpathogenswithepidemicpotentialhave 5 threatenedglobalhealthsecurityforthepastcentury.1Aswiththe 6 recentEbolaVirusDisease(EVD)epidemic,theZikaVirus(ZIKV) 7 outbreakhasyetagainsurprisedandoverwhelmedtheinterna- 8 tionalhealthcommunitywithanunexpectedeventforwhichit 9 mighthavebeenbetterprepared.
10 ZIKVwasfirstidentifiedinUgandain1947,wasalsofoundin 11 Gabonin 2007andmaybeendemic inmuchof tropicalAfrica 12 withoutreceiving muchattention.2 The current ZIKV epidemic 13 facingtheAmericas,3wasdeclareda‘‘PublicHealthEmergencyof 14 InternationalConcern(PHEIC)’’bytheWorldHealthOrganization 15 on 1st February 2016.4,5 Preceding the declaration of a Global 16 PublicHealthEmergencyby4dayswasthereleaseoftheUnited 17 Nationsreport‘‘ProtectingHumanityfromFutureHealth Crises.
18 ReportoftheHigh-levelPanelontheGlobalResponsetoHealth 19 Crises(UN26Jan2016)’’.6Thereportrecommendsthatcountries 20 be able to ‘‘If deemed necessary, diagnostic teams must be 21 deployedtoinvestigateunusualcases.Theseteamsmustalsohave 22 accesstolaboratorycapacitiestotestsamplesandtoproviderapid 23 testresults.’’6Thisissimplynotrealisticforthemajorpartofthe 24 UNmembercountries.
25 TheZIKVoutbreakhasspreadfurtherintoSouth-andCentral 26 America, into the Caribbean and will most likely spread into 27 SouthernUnitedStatesinareaswhereAedessppmosquitoesare 28 present.7ThereisalsoariskofZIKVintroductionintoSouthern 29 EuropewhereAe. albopictusmosquitoes arepresent.8TheWHO 30 ‘‘Zika strategic response framework and joint operations plan, 31 January-June2016’’describesthecurrentglobaldistribution,the 32 spread and nature of ZIKV infection as well as its potential 33 associationwithmicrocephalyand neurological complications.7 34 Thereportalsohighlightsaclearneedforaccurateandscalable 35 surveillancemethods,and emphasizestheneedtoincrease the 36 capacitytodiagnoseZIKAininfectedcountries,forimprovingdata 37 collection,surveillanceandvectorcontrol,and6MillionUSDhas 38 beenallocated to research. Howeverthe plan expects national 39 authoritiestoestablishlaboratorytesting.
40 ThepresentZIKVoutbreakagainexposesanunpreparedglobal
41 publichealthsystem.
42 Surveillanceofinfectionsisbasedonreportingcasesofillness,
43 oftensyndromicreportingofCNSorpulmonaryinfectionsamong
44 others,butunspecifiedbrieffebrileillnessesarerarelyreported,
45 even in pregnant women. In addition, assigning a possible
46 diagnosistosyndromicsurveillancerequiressuitablelaboratory
47 tests to be readily available for the causative agent and a
48 considerablelaboratorycapacity. Duringthefirstsix monthsof
49 theEbolavirusdisease(EVD)epidemicinWestAfrica,theweak
50 diagnostic laboratorycapacity in theaffectedcountries wasan
51 importantfactorintherapidspreadoftheoutbreak.9Asaresultof
52 intenseinternationalefforts,over27laboratorieswereestablished
53 to provide rapid in-country testing for Ebola virus. These
54 laboratories included both mobile and temporary laboratories
55 equippedtodomoleculardiagnostictestingandseverallaborato-
56 riestoprovidelocalgenomicsequencingofthevirustohelpin
57 contacttracing.However,sincethelaboratoriesweremostlyrun
58 byNonGovernmentalOrganizationsandvolunteersfromoverseas
59 publichealthlaboratories,mostoftheseeffortsprovidedonlya
60 temporarysolution,ratherthanalong-termsustainablesolution.
61 Furthermoretheselaboratorieswerefocusedonasingle,known
62 infection.
63 Thegreatestlaboratoryneedforepidemiologicalsurveillance
64 andclinicalmanagementfortheongoingZIKVoutbreakinBrazil
65 andLatinAmericaisforaneasytouse,robust,affordable,rapid,
66 sensitive, and specific diagnostic test for ZIKV. The current
67 estimatesofthenumberofinfectionsis134,460suspectedcases,
68 2,765 confirmed and 12 fatal outcomes, constantly rising.10
69 CurrentdiagnostictestsforZIKVarelimited;11thecurrentgold
70 standardtestisRT-PCRbutthisremainsunavailabletomostclinics
71 duetotheassociatedcostandashortageoftrainedpersonnel.The
72 urgent needfor newmethodsfor diagnostics that arescalable,
73 accurate and accessible were highlighted in the recent WHO
74 report.7WhiletheWHOhascalledforstrengtheningofnational
75 capabilities, most national public health reference laboratories,
76 where they exist, do not have the equipment or expertise to
77 identifyunknownpathogensinclinicalsamples,orinmanycases
78 even to look for the many known pathogens that may be
79 uncommontotheirowngeographicalarea.
80 InthepresentZIKVoutbreak,itisdifficulttofullyunderstand
81 how the infectioncould spread forovera decadein Asia and
82 the Pacific without being picked up by ongoing surveillance
83 programs.
InternationalJournalofInfectiousDiseasesxxx(2016)xxx–xxx
Keywords:
Zikavirus Emergingpathogens laboratory diagnostics surveillance publichealth GModel
IJID25531–3
Pleasecitethisarticleinpressas:ZumlaA,etal.Zikavirusoutbreakandthecaseforbuildingeffectiveandsustainablerapiddiagnostics laboratorycapacityglobally.IntJInfectDis(2016),http://dx.doi.org/10.1016/j.ijid.2016.02.1007
ContentslistsavailableatScienceDirect
International Journal of Infectious Diseases
j o urn a l hom e pa ge : ww w. e l s e v i e r. c om/ l o ca t e / i j i d
http://dx.doi.org/10.1016/j.ijid.2016.02.1007
1201-9712/ß2016PublishedbyElsevierLtdonbehalfofInternationalSocietyforInfectiousDiseases.ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://
creativecommons.org/licenses/by-nc-nd/4.0/).
84 Obvious questionsarise: Havegeneticchanges resultedin a 85 morepathogenicviruswherepreviousexposuredoesnotprovide 86 protective immunity? After all, ZIKV associated microcephaly, 87 Guillain-Barre´ andretinitishavenotbeenreportedfromAsiaor 88 Africa.AresimilarvirusescirculatinginAsiaandAfricaprovidinga 89 certain degree of cross protection, alleviating the symptoms 90 whereas the population in the Americas is immunologically 91 naı¨ve?2 Hastheviruschangedtobecomebetteradaptedtothe 92 Aedes spp mosquito making transmission more efficient? At 93 presentwe simplydon’t know,but manyscientists around the 94 worldhaverecognizedtheurgencywithwhichweneedtoanswer 95 thesequestionsandstudiesareongoing.
96 Thepublichealthcommunityhasoverthepasttwentyyears 97 expandedsyndromicsurveillancetoless traditional approaches 98 includingdatamining,analysisofinternetsearchtrendsaswellas 99 monitoring the consumption of certain drugs as indicators of 100 potential outbreaks etc.12 However, without proper and rapid 101 laboratorybackup,syndromicsurveillancecannotprovideafull 102 solutiontotheproblemandthuswilldelaytheimplementationof 103 informedpublichealthmeasures.Wehavepreviouslyhighlighted 104 theconstantthreatofnewemergingvirusestoAfricaandthelack 105 oflaboratoryinfrastructureinAfricatoallowthemonitoringofthe 106 existenceandspread ofnewinfectiousdiseases threatslikethe 107 MiddleEastRespiratorySyndrome,MERS,13andre-emergingones 108 likeEbolaVirusDisease.9Despitethis,thereappearstobealackof 109 awarenessofthisurgentbutunmetneed.
110 ThereisnowacallforareorganizationoftheWHOtobebetter 111 abletocopewithoutbreaks.14Whilethisisawelcomeinitiative, 112 wefearthatagainemphasis willbeplacedon surveillanceand 113 reportingandnotonlaboratorycapacity.Thecallforupgrading 114 national capacity in detecting and analyzing new or emerging 115 pathogensisinprinciplecorrect,butitmustberealizedthatthe 116 capacitytoperformtherequiredanalysislookingfornew,sofar 117 unknownpathogens, or known but unexpected pathogens and 118 analyzingthevastamountofdatafromgenomicstudies,canat 119 presentbedoneinaveryfewplaces.AsexamplesNipahvirusand 120 SARSwasidentifiedbytheCDCandMERSbytheErasmusMedical 121 Center,Netherlands notnational laboratories.15–17 Except for a 122 verylimitednumberofcountries,onlyacademiccentershavethe 123 capacity to perform this type of analysis. However academic 124 centersareinvariablyfundedbyresearchgrantsanditisthusnot 125 certainthattheappropriatesampleswillreachsuchlaboratories 126 andagainnotcertainthattherightanalysiswillbeperformedand 127 in time – it has to fit into the research strategy and is thus 128 haphazard.
129 Toadequatelyaddresstheglobalconcernoverpreparednessto 130 identify the next emerging global infectious disease threat, 131 countriesrequirehighlevellaboratorycapacitywiththecapacity 132 toundertakediagnosticsandgenomics,allowingtheidentification 133 ofneworemergingpathogens,aswellasmolecular analysisto 134 allowthe identification of antimicrobial resistance. The recent 135 studyofHIVresistancetotenofovirshowedanalarmingspreadof 136 tenofovirresistance,whichagainillustratethatthedevelopment 137 of infrastructure and surveillance without proper laboratory 138 backup – in this case drug susceptibility testing of HIV – will 139 resultinlong-termfailureoftheinterventions.18Thisalsoapplies 140 tosurveillanceofMDR-andXDRTB,withoutsusceptibilitytesting 141 new drugs cannot be introduced in patient care.19 This need 142 exceeds what is possible to establish in most countries even 143 industrialized countries. The international community must 144 consider the longevity of their support. Investment in human 145 resources from affected or potentially affected countries have 146 startedwiththeEbolacrisisbutthiseffortsseemnotbesustained 147 becausewhenthedangerdisappearssodoestheinterestofdonors.
148 Sub-Saharan African countries have suffered fromrecurrent 149 outbreaks of new and emerging infectious diseases. Regional
150 public health laboratory networks established by WHO AFRO
151 and its Member States, along with their technical partners,
152 undertake thereportingof these outbreaks.However muchof
153 sub-Saharan Africa have weak health systems, inadequate
154 resources, and poor capacity to identify and respond quickly
155 and effectively to disease outbreaks, making them very
156 vulnerabletothedevastatingeffectsofmostinfectiousdiseases
157 epidemics.ThescaleandoverwhelmingeffectsoftherecentEVD
158 epidemicinWestAfricaclearlydemonstratesthis.Thissituation
159 iscompoundedbylackofpreparednessandcapacitytoconduct
160 comprehensive and well-coordinated research in response to
161 suchdiseasethreats.
162 The establishment of high quality laboratory capacity will
163 requirecarefulreviewofexistingstructuresandcapacity,mapping
164 ofthecurrentdiagnosticcapacityofnationalreferencelaboratories
165 forallthe47MemberStatesinAFRO,20,21mostprobablysharing
166 referencelaboratoryfacilitiesbetween severalcountries Oppor-
167 tunities now presented by Europe-Africa initiatives like the
168 European & Developing Countries Clinical Trials Partnership
169 (EDCTP)mustbeseized.22
170 Itis importantthatinvestmentsinto developing laboratory
171 capacity within countries are tailored towards moving away
172 fromtheage-oldsinglepathogenscreeningapproach.Advances
173 in molecularbiology,23,24 andothertechnologies,25 nowallow
174 for rapidscreening formultiplepathogens andtheir antibiotic
175 sensitivity patterns and reporting them within hours.26,27
176 There is also a need to establish sentinel regional centres in
177 each continent, which can provide high level laboratory
178 supportandanalysistonationalgovernmentsandinternational
179 organizations.
180 Such centersshould be established with additional support
181 fromindustryandinternationaldonorscomparabletoTheGlobal
182 FundtoFightAIDS,TuberculosisandMalariaandinstrumentsfor
183 sharingdatawithindustry established.Thecentersshouldalso
184 havetheresponsibilityforsafelyandrapidlytransportingsamples,
185 sothataninterestingsamplefromforinstanceSouthSudanisjust
186 aphonecallawayfrombeingpickeduponlocation,transported
187 andanalyzednomatterwhetheritisaHIVorTBtreatmentfailure
188 orfeverofunknownoriginwithrespiratorysymptoms.
189 This would fill current gaps in surveillance and diagnostic
190 capabilitiestomonitor theintroductionsofneworre-merging
191 pathogenswithepidemicpotentialintoacommunity.Callsfor
192 thecreationbytheWorldHealthOrganization(WHO)ofanew
193
‘‘Centre for Emergency Preparedness and Response’’ that has 194 realcommandandcontrolcapacityandhasthepersonneland
195 laboratory resourcesitneeds to respondshould besupported
196 strongly since coordination and surveillance is critical to
197 preventing another disastrous epidemic like EVD. However
198 we fear that without support from industry funding will be
199 inadequate.WehopethattheZIKVoutbreakwillturnouttobe
200 stormin ateacup.
201 Authordeclarations:Allauthorshaveanacademicinterestin
202 laboratorydiagnosticsandinfectiousdiseases.Authorsdeclareno
203 conflictsofinterest.
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289 290 291 292 AlimuddinZumlaaQ1
293 IanGoodfellowb
294 FrancisKasoloc
295 FrancineNtoumid
296 PhilippeBuchyeQ2
297 MatthewBatesf
298 EsamIAzharg
299 MatthewCottenh
300 EskildPeterseni,*
a 301
DivisionofInfectionandImmunity,UniversityCollegeLondonand 302 NIHRBiomedicalResearchCentre,UCLHospitalsNHSFoundation
303 Trust,London,UK
b 304
DivisionofVirology,DepartmentofPathology,Universityof 305 Cambridge,Addenbrooke’sHospital,HillsRoad,CambridgeUKand
306 SchoolofPublicHealth,UniversityofMakeni,SierraLeone
c 307
CountryandInter-countrySupport,OfficeoftheRegionalDirector, 308 WHO-AFRO,Brazzaville,RepublicofCongo
dFondationCongolaisepourlaRechercheMe´dicaleandUniversity 309 310 MarienNgouabi,Brazzaville,RepublicofCongo,andInstitutefor
311 TropicalMedicine,UniversityofTu¨bingen,Germany
ePhilippeBuchy,GlaxoSmithKlineVaccines,R&DAsia-Pacific, 312 313 GatewayWest,Singapore
fUNZA-UCLMSResearchandTrainingProject,UniversityTeaching 314 315 Hospital,Lusaka,Zambia
gSpecialInfectiousAgentsUnit,KingFahdMedicalResearchCentre, 316 317 andMedicalLaboratoryTechnologyDepartment,FacultyofApplied
318 MedicalSciences,KingAbdulazizUniversity,Jeddah,SaudiArabia
hTheWellcomeTrustSangerInstitute,Cambridge,UK 319
i 320
UniversityofAarhus,DenmarkandTheRoyalHospital,Muscat,Oman 321 CorrespondingEditor:EskildPetersen,Aarhus,Denmark.
322
*Correspondingauthor.UniversityofAarhus,DenmarkandThe 323 RoyalHospital,Muscat,Oman.
324 E-mailaddresses:[email protected],
325 [email protected](A.Zumla).,
326 [email protected](I.Goodfellow).,
327 [email protected](F.Kasolo).,
328 [email protected](F.Ntoumi).,
329 [email protected](P.Buchy),
330 [email protected](M.Bates).,
331 [email protected](E.I.Azhar).,
332 [email protected](M.Cotten).,
333 [email protected](E.Petersen).
334 29February2016
335 Accepted29February2016 Editorial/InternationalJournalofInfectiousDiseasesxxx(2016)xxx–xxx 3 GModel
IJID25531–3
Pleasecitethisarticleinpressas:ZumlaA,etal.Zikavirusoutbreakandthecaseforbuildingeffectiveandsustainablerapiddiagnostics laboratorycapacityglobally.IntJInfectDis(2016),http://dx.doi.org/10.1016/j.ijid.2016.02.1007