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HAL Id: pasteur-01665271

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Crimean-Congo hemorrhagic fever serosurvey in at-risk professionals, Madagascar, 2008 and 2009

Soa Fy Andriamandimby, Philippe Marianneau, Jean-Théophile Rafisandratantsoa, Pierre E. Rollin, Jean-Michel Heraud, Noël Tordo,

Jean-Marc Reynes

To cite this version:

Soa Fy Andriamandimby, Philippe Marianneau, Jean-Théophile Rafisandratantsoa, Pierre E. Rollin, Jean-Michel Heraud, et al.. Crimean-Congo hemorrhagic fever serosurvey in at-risk professionals, Madagascar, 2008 and 2009. Journal of Clinical Virology, Elsevier, 2011, 52 (4), pp.370 - 372.

�10.1016/j.jcv.2011.08.008�. �pasteur-01665271�

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JournalofClinicalVirology52 (2011) 370–372

ContentslistsavailableatScienceDirect

Journal of Clinical Virology

j ourna l h o me p a g e :w w w . e l s e v i e r . c o m / l o c a t e / j c v

Short communication

Crimean-Congo hemorrhagic fever serosurvey in at-risk professionals, Madagascar, 2008 and 2009

Soa Fy Andriamandimby

a,∗

, Philippe Marianneau

b

, Jean-Théophile Rafisandratantsoa

a

, Pierre E. Rollin

c

, Jean-Michel Heraud

a

, Noël Tordo

d

, Jean-Marc Reynes

a

aNationalReferenceLaboratoryforArbovirusesandVirusesofHemorrhagicFever,VirologyUnit,InstitutPasteurdeMadagascar,Routedel’InstitutPasteur,BP1274,Antananarivo 101,Madagascar

bOIEReferenceLaboratoryforRVFVandCCHFV,AgenceNationaledeSécuritéSanitaire,31AvenueTonyGarnier,69394LyonCedex07,France

cViralSpecialPathogensBranch,WHOCollaborativeCentreforViralHemorrhagicFevers,CentersforDiseaseControlandPrevention,1600CliftonRoadMSG-14,Atlanta,GA30333, USA

dNationalReferenceCentreforViralHemorrhagicFever,WHOCollaborativeCentreforArbovirusesandViralHemorrhagicFever,OIEReferenceLaboratoryforRVFVandCCHFV, InstitutPasteur,21AvenueTonyGarnier,69365LyonCedex07,France

a r t i c l e i n f o

Articlehistory:

Received13May2011

Receivedinrevisedform25July2011 Accepted8August2011

Keywords:

Crimean-Congohemorrhagicfever Madagascar

Surveys

a b s t r a c t

Background:Crimean-Congohemorrhagicfever(CCHF)isazoonoticarboviralinfectionwithhemorrhagic manifestationandoftenafatalending.Humanbecomeinfectedmainlythroughtickbiteorbycrushing infectedtick,bycontactwithbloodortissuesfromviraemiclivestockorpatient.CCHFvirus(CCHFV)has beenisolatedonceinMadagascarbutdataontheepidemiologyofthediseaseinthecountryarevery scarce.

Objectives:ToinvestigatethecirculationandthegeographicdistributionofCCHFVinfectionamongat riskpopulationinMadagascar.

Studydesign:Anationalcross-sectionalserologicsurveywasperformedin2008–2009amongslaughter- houseworkers.

Results:Atotalof1995workerswereincluded.ArecentCCHFVinfectionwasdetectedin1ofthe1995 participants(0.5‰;95%confidenceinterval[CI]:0–0.15%),andapastCCHFVinfectionwasdetectedin 15participants(0.75%;95%CI:0.37–1.13%).

Conclusion:Overall,thepercentageofCCHFVinfectionseeninMadagascaramongat-riskprofessionals isverylowcomparedtoendemiccountries.Anassessmentoftheprevalenceinlivestockasasensitive indicatorofCCHFVactivitymustbeconsideredinordertoconfirmthelackortheweakendemicityof CCHFinMadagascar.

© 2011 Elsevier B.V. All rights reserved.

1. Background

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne diseasecaused byavirus(CCHFV)belongingtothefamily Bun- yaviridae, genus Nairovirus (reviewed in 1, 2).This zoonosis is largelydistributedinAfrica,Asia,MiddleEastandsouthernEurope (Balkan Peninsula). Hyalomma spp. is the most important and widely distributed tick vector, but other genera (Rhipicephalus, Boophilus, Dermacentor, and Ixodes)may have beencontributed toCCHFVecologicalcycle. Ruminants,but alsosmallterrestrial mammalsandbirdsareinvolvedinanenzootictick-vertebrate-

Abbreviations: CCHF,Crimean-Congohemorrhagicfever;CCHFV,Crimean- Congohemorrhagicfevervirus;ELISA,enzyme-linkedimmunosorbentassay;CDC, CentersforDiseaseControlandPrevention.

Correspondingauthor.Tel.:+261202241272;fax:+261202241534.

E-mailaddress:soafy@pasteur.mg(S.F.Andriamandimby).

tickcycle.Humanbecomeinfectedthroughtickbiteorbycrushing infectedtick,bycontactwithbloodortissuesfromviraemiclive- stock,orbyunprotectedcontactwithbiologicalfluidsofaCCHF patientduringtheacutephaseofinfection.Diseaseisseenonlyin humansandfrequentlyfatalwithseverehemorrhagicsigns.Treat- mentissymptomaticandtodate,novaccineisavailable.1,2

In Madagascar, CCHFV was isolated only once, from Rhipi- cephalus(Boophilus)microplustickscollectedoncattle,inMarch 1985,inthemainslaughterhouseinAntananarivo.Animalswere comingfromTsiroanomandidy,inthehighlands,150kmWestfrom Antanananarivo.Itwasthelargestlivemarketinthecountryreceiv- ingcattlefromallplacesinMadagascar.3

Phylogenetic studiesbased on partialSsequences indicated thattheMalagasystrainwasclosertostrainsisolatedinMiddle- East and Asia than to African isolates.4 The only serological evidenceofCCHFVhumaninfection(usingimmunofluorescence assay) was demonstrated in 2 out of 149 individuals sampled in 1988 in Mandoto, a cattle breeding area in the highlands.5 1386-6532/$seefrontmatter© 2011 Elsevier B.V. All rights reserved.

doi:10.1016/j.jcv.2011.08.008

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S.F.Andriamandimbyetal./JournalofClinicalVirology52 (2011) 370–372 371

DataonCCHFepidemiologyinMadagascarareconsequentlyvery limited.

2. Objectives

Toinvestigatethecirculationandthegeographicaldistribution ofCCHFVinfectionamongatriskpopulationinMadagascar.

3. Studydesign

Weperformedanationwideserologicalsurvey,fromSeptember 2008throughMay2009,among1995humanvolunteersathigh risksofzoonoticinfectionasCCHF.6Thesevolunteerswerepeo- plelivingin106outof111administrativedistrictsofMadagascar andworkinginslaughterhouses,exposedtofreshmeatorbloodof livestocksinceatleast2007.ThestudywasapprovedbytheMala- gasyNationalEthicalCommittee.Informedwrittenconsentwas obtainedfromtheparticipants.DetectionofIgMandIgGantibodies againstCCHFVwasperformedbyELISAaspreviouslydescribed.7 Briefly,followingheatanddetergentinactivation,seraweretested byCCHFV-specificIgMandIgGELISAs.Theassayswerecompleted usinginactivatedCCHFV-infectedVeroE6cellantigensandunin- fectedVeroE6cellantigens,andusingfourdilutionsofeachserum (1/100,1/400,1/1600,1/6400).Titersandthecumulativesumof opticaldensitiesofeachdilution(SUMOD)minusthebackground absorbanceofuninfectedcontrolVeroE6cells(adjustedSUMOD) wererecorded.Resultsoftheassaysforserawereconsideredposi- tiveonlyiftheadjustedSUMODandtiterwereabovepreestablished conservativecutoffvalues,whichweresetforIgMELISA(≥0.75and

≥1/400)andIgGELISA(≥0.95and≥1/400).Positivesamplesand 3%ofthenegativesamplestestedintheInstitutPasteurinMada- gascar(IPM)weresenttotheInstitutPasteurinLyonandtothe CDCinAtlantatovalidatetheIPMELISAresults.

4. Results

Atotalof 1995persons,aged 15–85yearsparticipatetothe study.Themedian agewas34 years(36missingdata). Thesex ratiowas13.7(sixmissingdata).ArecentCCHFVinfection(pres- enceofIgM againstCCHFVandlackofIgG againstCCHFV)was detectedin1ofthe1995participants(0.5‰;95%confidenceinter- val[CI]:0–0.15%),and a pastCCHFV infection(presenceof IgG againstCCHFVandlack ofIgMagainstCCHFV) wasdetectedin 15participants(0.75%;95%CI:0.37–1.13%).Titerswere400,1600, and6400for11,3and1participants,respectively.CCHFVantibody positivesubjectsweredetectedin14ofthe106districtstestedsug- gestingascattereddistribution(Fig.1).Theseropositivitywasnot significantlyfoundassociatedwithage,sexorlocationofactivity ofparticipants(datanotshown).

5. Discussion

Overall,thepercentageof CCHFVinfectionseeninMadagas- car among at-risk professionals is very low compared to those observedin endemiccountrieslikeMauritania (7%)and United ArabEmirates(6%).7,8Thisobservationmaybeexplainedbythe lackofticksofthegeneraHyalommainMadagascar.9Rhipicephalus (Boophilus)microplus,thespeciesfoundinfectedbyCCHFVinMada- gascariswidelydistributedinthecountryupto1950mofaltitude (Stachurski,pers.comm.).However,thevectorcompetenceofthis specieshasnotbeendemonstratedinthelaboratory.2

Thelowpercentageofdetectionofhumanantibodiesagainst CCHFV and the scattered geographic distribution may be the consequenceofrepeatedintroductionsofinfectedanimals,large movementsof domesticruminantsinthecountry,and abortive

Fig. 1.Distribution of Crimean-Congo hemorrhagic fever (CCHF) in the 111 administrative districts from Madagascar, 2008 and 2009. Antibody data for immunoglobulin(Ig)levelsagainstCCHFvirusinserumsamplesfromat-riskspro- fessionalsareindicatedwithdarkverticals(IgMpositiveandIgGnegative),with darkhorizontals(IgGpositiveandIgMnegative),withdarkupwarddiagonals(IgG andIgMnegative).Nosamplewasreceivedfromdistrictsshowninwhite.

circulationsofCCHFVwithinthecountry.ForRiftValleyfever,we havegeneticevidencethatoutbreaksinMadagascarresultedfrom multiplevirusintroductionsfromtheeastAfricamainlandrather thanenzooticmaintenance.10Livestockmovementswerealready implicatedinthelargediffusionofRVFVduringthe2008–2009 outbreak.6

SincethefirstinvestigationscarriedoutbytheInstitutPasteur inthe1970s,16arbovirusesorrelatedviruseshavebeenisolated in Madagascar.9,11–13 CCHFV is the only member of the genus Nairovirusdetectedintheisland.However,wecannotexcludethe presenceof anundected nairovirus closetoCCHFVlike viruses fromtheNairobisheepdiseasegroupincludingtheeponymvirus and Dugbe virus, present and widespread in continental Africa (http://www.cdc.gov/nczved/divisions/dvbid/arbovirus.html).

Consequently,theoccurrenceofcross-reactioninourdetectionof antibodiesagainstCCHFV,ifany,highlightstheverylowcirculation ofCCHFVinMadagascar.

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372 S.F.Andriamandimbyetal./JournalofClinicalVirology52 (2011) 370–372

Anassessmentoftheprevalenceinlivestockasasensitiveindi- catorofCCHFVactivitymustbeconsideredinordertoconfirmthe lackortheweakendemicityofCCHFinMadagascar.

Funding

ThisworkwasfundedbyInstitutPasteurdeMadagascar.

Competinginterests

Thereisnoconflictofinterestandabsenceofanyrelationshipor anydegreeofconflictingordualinterest,financialorofanyother naturethatmayaffectprofessionaljudgmentinrelationtothis article.

Ethicalapproval

EthicalApprovalwasgivenbythe“ComitéNationald’Ethique”

ofMadagascar.Judgement’sreferencenumber:O22-CE/MINSAN.

Acknowledgments

WethankhealthcareofficersatMinistryofPublicHealthof Madagascarfortheirassistanceincollectingthedataandsamples ofpatients.

References

1.Whitehouse CA. Crimean-Congo hemorrhagic fever. Antiviral Res 2004;64:145–60.

2.HoogstraalH.Epidemiologyoftick-borneCrimean-Congohemorrhagefeverin Asia,Europe,andAfrica.JMedEntomol1979;15:307–417.

3.MathiotCC,FontenilleD,DigoutteJP,CoulangesP.FirstisolationofCongo- Crimeanhaemorrhagic fever virus in Madagascar.Ann Inst Pasteur Virol 1988;139:239–41.

4.RodriguezLL,MaupinGO,KsiazekTG,RollinPE,KhanAS,SchwarzTF,etal.

MolecularinvestigationofamultisourceoutbreakofCrimean-Congohem- orrhagicfeverintheUnitedArabEmirates.AmJTropMedHyg 1997;57:

512–8.

5. MathiotCC,FontenilleD, GeorgesAJ,CoulangesP.Antibodiestohaemor- rhagicfevervirusesinMadagascarpopulations.TransRSocTropMedHyg 1989;83:407–9.

6.AndriamandimbySF,Randrianarivo-SolofoniainaAE,JeanmaireEM,Ravololo- mananaL,RazafimanantsoaLT,RakotojoelinandrasanaT,etal.RiftValley feverduring rainyseasons,Madagascar,2008and 2009.EmergInfect Dis 2010;16:963–70.

7.KhanAS,MaupinGO,RollinPE,NoorAM,ShurieHH,ShalabiAG,etal.An outbreakofCrimean-CongohemorrhagicfeverintheUnitedArabEmirates, 1994–1995.AmJTropMedHyg1997;57:519–25.

8. Nabeth P, Cheikh DO,Lo B, Faye O, Vall IO,Niang M, et al. Crimean- Congo hemorrhagic fever, Mauritania. Emerg Infect Dis 2004;10:

2143–9.

9.FontenilleD.ArbovirustransmissioncyclesinMadagascar.ArchInstPasteur Madagascar1989;55:1–317[inFrench].

10.CarrollSA,ReynesJM,KhristovaML,AndriamandimbySF,RollinPE,Nichol ST.GeneticevidenceforRiftValleyFeveroutbreaksinMadagascarresulting fromvirusintroductionsfromtheEastAfricanmainlandratherthanenzootic maintenance.JVirol2011Jul;85(13):6162–7.

11.RoussetD,RandriamparanyT,MaharavoRahantamalalaCY,Randriamahefa N,ZellerH,Rakoto-AndrianariveloM,etal.AfricanSwineFeverintroduction intoMadagascar,historyandlessonsfromanemergence.ArchInstPasteur Madagascar2001;67:31–3.

12.RatsitorahinaM,HarisoaJ,RatovonjatoJ,BiacabeS,ReynesJM,ZellerH,etal.

OutbreakofdengueandChikungunyafevers,ToamasinaMadagascar,2006.

EmergInfectDis2008;14:1135–7.

13. RazafindratsimandresyR,JeanmaireEM,CounorD,VasconcelosPF,SallAA, ReynesJM.Partialmolecularcharacterizationofalphaherpesvirusesisolated fromtropicalbats.JGenVirol2009;90:44–7.

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