Prevalence of Trypanosoma cruzi/HIV coinfection in southern Brazil

w w w . e l s e v ie r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Brief

communication

Prevalence

of

Trypanosoma

cruzi/HIV

coinfection

in

southern

Brazil

Dulce

Stauffert

_,

_Mariangela

_Freitas

_da

_Silveira

_,

_Marília

_Arndt

_Mesenburg

_,

Adriane

Brod

Manta

_,

_Alessandra

_da

_Silva

_Dutra

_,

_Guilherme

_Lucas

_de

_Oliveira

_Bicca

_,

Marcos

Marreiro

Villela

a_{UniversidadeFederaldePelotas,FaculdadedeMedicina,DepartamentodeSaúdeMaterno-Infantil,Pelotas,RS,Brazil} b_{UniversidadeFederaldePelotas,InstitutodeBiologia,ProgramadePós-graduac¸ãoemParasitologia,Pelotas,RS,Brazil} c_{UniversidadeFederaldePelotas,ProgramaPós-graduac¸ãoemEpidemiologia,Pelotas,RS,Brazil}

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Articlehistory:

Received13July2016 Accepted13October2016 Availableonline1December2016

Keywords:

Chagasdisease

Trypanosomacruzi

AIDS

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Chagasdiseasereactivationhasbeenadefiningconditionforacquiredimmunedeficiency syndromeinBrazilforindividualscoinfectedwithTrypanosomacruziandHIVsince2004. Althoughthefirstcoinfectioncasewasreportedinthe1980s,itsprevalencehasnotbeen firmlyestablished.Inordertoknowcoinfectionprevalence,across-sectionalstudyof200 HIVpatientswasperformedbetweenJanuaryandJuly2013inthecityofPelotas,insouthern RioGrandedoSul,anendemicareaforChagasdisease.Tensubjectswerefound posi-tiveforT.cruziinfectionbychemiluminescencemicroparticleimmunoassayandindirect immunofluorescence.Thesurveyshowed5%coinfectionprevalenceamongHIVpatients (95%CI:2.0–8.0),whichwas3.8timesashighasthatestimatedbytheMinistryofHealthof Brazil.Sixindividualshadaviralloadhigherthan100,000copiesper␮L,astatistically signif-icantdifferenceforT.cruzipresence.Thesefindingshighlighttheimportanceofscreening HIVpatientsfromChagasdiseaseendemicareas.

©2016SociedadeBrasileiradeInfectologia.PublishedbyElsevierEditoraLtda.Thisisan openaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/ by-nc-nd/4.0/).

American trypanosomiasis,also known as Chagas disease (CD),isa neglectedtropical condition.1,2 _{TheWorld Health}

Organizationestimatesthateightmillionpeopleworldwide arepresentlyinfectedwithTrypanosomacruzi.2

CDchronicinfectionischaracterizedbylowparasitelevels inthebloodandincardiacand/ordigestivetracttissues,which typicallypersiststhroughoutlife.Thechronicinfectionmay

∗ _{Correspondingauthor.}

E-mailaddress:marcos.villela@ufpel.edu.br(M.M.Villela).

manifestitselfasindeterminateorsymptomatic,and20–30% ofChagaspatientsdevelopcardiomyopathy,megaesophagus, ormegacolon.3_{Nevertheless,thediseasemayseriouslyaffect}

transplantrecipients,cancerpatients,andindividualsliving withAIDSduetoimmunosuppression.4,5_{Indeed,T.cruzi,like}

otherinfectiousorganisms,isanopportunisticprotozoanin thesepatients.6,7

http://dx.doi.org/10.1016/j.bjid.2016.10.006

1413-8670/©2016SociedadeBrasileiradeInfectologia.PublishedbyElsevierEditoraLtda.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).

Table1–SociodemographicandbehavioralprofileofpatientssurveyedforTrypanosomacruzi/HIVcoinfectioninthe

extremesouthofBrazil.n=200.

Sociodemographicvariable n % Gender Male 99 49.5 Female 101 50.5 Age Upto29 41 20.5 30–39 51 25.5 40–49 53 26.5 50+ 55 27.5 Completedyearsof education 0–4 49 24.5 5–8 86 43.0 9+ 65 32.5

Maritalstatus Married 105 52.5

Single 76 38.0

Widowed 8 4.0

Divorced 11 5.5

Monthlyincomea _{<1minimumwage 117 58.5}

>1minimumwage 48 24.0 Nowage 35 17.5 Smoking Yes 174 87.0 No 26 13.0 Alcohol consumption Everyday 3 1.5 >onceaweek 45 22.5 <onceaweek 8 4.0 Never 144 72.0

Druguse Yes 26 13.0

No 174 87.0 Antiretroviral therapy Yes 143 71.5 No 57 28.5 CD4+_Tlymphocytes (cellsmm3₎ Upto350 51 25.5 >350 149 74.5

Viralload(copiesper ␮L)

<50 146 73.0

51–100,000 40 20.0

>100,000 14 7.0

a _{Minimumwage=R$780.00amonth,aboutU$250.00inJuly2015.}

MigrationfromruraltourbanareasinBrazilandotherLatin Americancountrieshasparticularlyincreasedtheprobability ofindividuals withChagas disease tocontractHIV.8,9

Con-sequently,Chagasdiseasereactivationincoinfectedpatients wasdeclared anAids-definingcondition in2004;asa con-sequence, the BrazilianNetwork ofCare and Studies onT. cruzi/HIV coinfection was created in 2006.8,10,11 _{The 2008}

Guidelines from the Brazilian Ministry of Health11

recom-mendedaChagasDiseaseserologicaltestforallHIVpatients, especially those from endemic areas, at the first medical assessment.

In those countries where CD is endemic, the coinfec-tionHIV/T.cruziraterangesfrom1.3%to7.1%,12_whereasin

Braziltheestimateis1.3%.11_{AccordingtodatafromHIV/AIDS}

reportsoftheMinistryofHealthinBrazil,theSouthernand Central-Westernregionsofthecountryhavethehighest num-berofreportedcases.Amongmunicipalitieswithmorethan 100,000inhabitants,thecityofPelotasoccupiesthetwentieth position,with5943cases.9_{Inthesamemunicipality,astudyof}

252HIV+_patients13_{measuredtheserologictestingindexfor}

Chagas,finding a3.2%rate(eightpatients),sevenofwhom

were negative fortrypanosomiasis and onehad no results availableinhismedicalrecord.Theauthorsexpressed con-cernonthelowserologictestingindexforCDinHIV+_patients,

sincethestudy wasconductedinanareaconsideredtobe endemicforthepresenceofT.cruzianditsvectors.14,15

Giventhelackofcoinfectiondatainendemicareas and the relevanceofthe topictopublic health,the aimofthis studywastoevaluatetheT.cruzi/HIVcoinfectionprevalence inpatientscaredforataspecializedservicecenterinthecity ofPelotas,RioGrandedoSulState,Brazil,aswellasto eval-uatecoinfectioncorrelation,ifany,withgender,age,CD4+_T

lymphocytes,andviralload.

Across-sectionalstudywasconductedwithpatientsbeing monitoredatinthe SpecialCareService(SCS)ofthe Med-icalSchooloftheFederalUniversity ofPelotas(UFPEL),Rio GrandedoSulState,Brazil.Thisserviceisapartnershipwith the MunicipalHealth Department of Pelotas, and provides caretopublichealthsystempatients.Thepopulationunder study comprisedof 200 HIV infectedpatients, characteriz-ingarepresentativeSCSsample.Theageofpatientsranged between18to80years,andincludedbothmaleandfemale

Table2–AssociationofTrypanosomacruzi/HIVcoinfectionintheextremesouthofBrazilwithsociodemographicfactors,

CD4+_{Tlymphocytes,andviralload.n=200,ofwhich10werecoinfected.}

Variable n % p-Valuea _{Oddsratio(95%CI)}b

Age Upto29 2 4.9 0.609 1 30–39 1 2.0 0.39(0.03–4.45) 40–49 4 7.7 1.63(0.28–9.34) 50+ 3 5.5 1.13(0.18–7.06) Gender Male 6 6.0 0.535 1 Female 4 4.0 0.63(0.02–2.33)

Completedyearsofeducation

0–4 4 8.2 0.461 1 5–8 3 3.5 0.41(0.09–1.89) 9+ 3 4.6 0.54(0.11–2.55) Maritalstatus Married 6 5.7 0.501 1 Single 2 2.6 0.44(0.09–2.27) Widowed 1 12.5 2.35(0.25–22.4) Divorced 1 9.1 1.65(0.18–15.11) Monthlyincome <1minimumwage 9 6.3 0.287 1 >1minimumwage 1 1.7 0.26(0.03–2.09) CD4+_{Tlymphocytes(cells/mm}3₎ Upto350 6 7.8 0.280 1 >350 4 4.0 0.49(0.13–1.82)

Viralload(copiesperL)

<50 3 4.1 0.027 1

50–100,000 1 2.4 0.58(0.07–5.00)

>100,000 6 23.1 7.00(1.5–32.23)

a _{Fisher’sexacttest.} b _{Logisticregression.}

patients.ThestudywasperformedbetweenJanuaryandJuly 2013.

Socioeconomic,demographic,andbehavioralinformation was collected according to a pre-tested structured ques-tionnaire.Thefollowing dataregardingsocioeconomic and demographicvariableswerecollected:residenceinaT.cruzi

endemicarea(yesorno),gender(maleorfemale),agegroup (upto29,30–39,40–49,50yearsorolder),educationinschool years(0–4,5–8,9ormore),maritalstatus(married,single, wid-owed,ordivorced),andmonthlyincome(uptooneormore thanoneminimumwage).Thefollowingbehavioralvariables wereobtained:smoking,currentlyoruptothemonthbefore theinterview(yesorno);alcoholintakecurrentlyoruptothe monthbeforetheinterview(lessthanonceaweek,morethan onceaweek,everyday,ornever);currentoccasionaldruguse (yesorno).Treatmentwithantiretroviraltherapy(yesorno), CD4+_{Tlymphocytes(upto350or>350cells/mm}3_),andviral

load (<50,51–100,000, or >100,000copies/␮L) were obtained frommedicalrecords.

Bloodsampleswere collectedandtestedforanti-T.cruzi

IgGattheClinicalAnalysisLaboratoryoftheFederal Univer-sityofPelotas.SampleswerefirsttestedbyChemiluminescent Microparticle Immunoassay(ARCHITECT Chagas®, Abbott). Positive results from this test were checked by indirect immunofluorescence (WAMA® Diagnóstica) according to manufacturer’sinstructions.Samplestestingpositiveonboth

assayswereconsideredinfected,andtestresultswere trans-ferredtopatientrecordsandmadeavailabletobothphysicians andpatients.

Sociodemographic,anti-T.cruziIgG,andbehavioralfactors wereanalyzedbydescriptivestatisticsusingStata®12 (Stata-CorpLP,CollegeStation,TX,USA).Foranalysisofcoinfection againstsociodemographicvariables,CD4+_{Tlymphocytes,and}

viral load Fisher’s exact test and logistic regression were usedtocompareproportionsandobtainoddsratios, respec-tively.

ThestudywasreviewedandapprovedbytheEthics Com-mittee of the Medical School of the Federal University of Pelotas, Brazil according to Resolution 466/12 on research involving human subjects ofthe BrazilianNational Health Council. Allsubjectsofthis researchwereadultsand were askedtosignaninformedconsentafterbeinginformedon thepurposeandproceduresofthestudy.

Table1showssociodemographicandbehavioral character-isticsofthe200patientswhoparticipatedinthestudy.There were norefusalsbyrespondentsduringtheresearch.49.5% (99)ofthe respondentsweremale and50.5% (101),female. Mostofthepatients(54%)were40yearsofageorolder,and 43% had 5–8 years of schooling, while52% were married. Amongthosewhoreportedhavinganincome(82.5%),58.5% earneduptooneminimumwage.Astobehavioralvariables, 87%smoked,28%haddrunkalcoholinthepreviousmonth

and87% hadneverusedillicitdrugs.Mostpatients (71.5%) were undergoing antiretroviral treatment and 74.5% ofthe patientshadLTCD4+_{counthigherthan350cells/mm}3_.

TenindividualstestedpositiveforT.cruzi,correspondingto 5%prevalence(95%CI:2.0–8.0)amongHIVpatients.Allwere onantiretroviraltherapy.Theonlyvariablesignificantly dif-ferentbetweencoinfectedandmonoinfectedpatientswasthe rateofviralloadhigherthan100,000copiesper␮L,asshown inTable2.

Ofthe200individualsevaluatedinthisstudy,10were diag-nosedwithcoinfectionT.cruzi/HIV(5%),arate3.8-foldhigher thanthe1.3%estimatebythe MinistryofHealthin2013.11

Thus,thesurveyhighlightsT.cruziasapotential opportunis-ticparasiteinHIVpatientsfromareaswhereChagasdisease isendemic,16 _{suchassouthernRioGrandedoSul,Brazil.A}

surveyofHIV/T.cruzicoinfectioninEuropeinpatientsfrom Bolivia,Argentina,orthe SouthernCone,confirmed a1.9% coinfection.16_{AstudyinArgentina,acountrywiththelargest}

numberofreportedcoinfectioncases,alongwithBrazil,17_the

prevalenceofT.cruzi/HIVcoinfectionwas4.2%,similartothat inthisstudy.18

Highviralloads andareductioninCD4+ _Tlymphocytes

canleadto immunosuppression,and may beconsidered a reactivationriskfactor,19_{althoughtherearenoreliable}

meth-odsofpredictingthisreactivation.Inthisstudy,mostpatients wereonantiretroviraltherapy,whichappearstopreventor controlChagasreactivation.4_{Indeed,the10coinfected}

indi-vidualsinthisstudyhadnosymptomsconsistentwithChagas reactivation.However,thesepatientsneedtobemonitored carefully,asmortalitymayreach80%iftreatmentisdelayed foratleast30daysaftertheonsetofChagassymptoms,while earlytreatmentreducesitto20%.10

As to the variables analyzed, there was a statistically significant association only for coinfection and viral load above100,000copies(OR=7.0).Althoughsuchassociationwas found,onecannotbesurewhetheritistheT.cruziparasitethat causedthisviralloadincrease.Nevertheless,evaluationshave shownanassociationbetweenCDreactivation,thedecrease inCD4+_{cellcount,andincreaseinviralload.}20_This

associa-tionwasnotobservedinthisstudy,onceCDreactivationcases werenotdetected.Therefore,otherdetailedreviewsonthis topicareneeded.

This coinfection has been poorly characterized, and remains unknown to or neglected by many health profes-sionals. Serological tests for Chagas disease in southern Brazil were requestedat thefirst medical appointmentfor only 3.2% of HIV cases, even though the 2013 Consen-susDocument of the Ministryof Health recommendsthat such tests be requested for all HIV patients at the first appointment.11,13

Duetothe possibility ofthe occurrenceofboth etiolog-ical agents in the same individual and the likely severity of this coinfection, it was concluded that the Ministry of Health guidelines as to the need for T. cruzi serological testsinHIV+ _{patientsfromCD endemicareas arerelevant.}

Our study showed a coinfection rate 3.8-fold higher than that estimated for Brazil. Furthermore, patients who have beenmadeawareofthisconditioncanbenefitfrom special-izedmedicalcare,thusavoidingeventualdamageresulting fromit.

Funding

Provided by Programa de Apoio à Pós-Graduac¸ão (PROAP), Coordenac¸ãodeAperfeic¸oamentodePessoaldeNívelSuperior (CAPES),Brasília,DF,Brazil.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgements

ToSCSstaffandthepatientswhoparticipatedinthesurvey.

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