Tuberculosis contact tracing among children and adolescent referred to children's hospital in Rio de Janeiro, Brazil

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

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Original

article

Tuberculosis

contact

tracing

among

children

and

adolescent

referred

to

children’s

hospital

in

Rio

de

Janeiro,

Brazil

Angela

Marcia

Cabral

Mendonc¸a

∗

,

Afrânio

Lineu

Kritski,

Clemax

Couto

Sant’Anna

SchoolofMedicine,UniversidadeFederaldoRiodeJaneiro(UFRJ),RiodeJaneiro,RJ,Brazil

a

r

t

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o

Articlehistory:

Received28September2014 Accepted22December2014 Availableonline27January2015

Keywords:

Preventivetherapy Operationalresearch Pediatrictuberculosis

a

b

s

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Objective:Todescribetheinvestigationoflatenttuberculosisinfectionandindicationfor isoniazidpreventivetherapyinchildrenandadolescentsevaluatedatthechildren’shospital.

Methods:Thisretrospectivestudyexaminesalllatenttuberculosisinfectionsubjectswith indicationforisoniazidpreventivetherapyattendedduring2002–2009atthepulmonology outpatientclinicfromchildren’shospitalinRiodeJaneiro,Brazil.Thesubjectswere clas-siﬁedintothreegroupsbyorigin:(G1)primaryandsecondaryhealthunits;(G2)children’s hospital-pulmonologyoutpatientclinic;and(G3)children’shospital-specialtyoutpatient clinics.TheassociationbetweenthevariablesexaminedandG1wasanalyzedusing uni-variateanalysis.

Results:Ofthe286latenttuberculosisinfectioncasesincluded169(59.1%)werefromG1, 56(19.6%)fromG2,and61(21.3%)fromG3.Latenttuberculosisinfectiondiagnosiswithout isoniazidpreventivetherapyprescriptionwaspresentin142(49.6%)casesbeforearrival atthepulmonologyoutpatientclinic:135(95.1%)fromG1,three(2.1%)fromG2,andfour (2.8%)fromG3.VariablesassociatedwithG1werepresenceofisoniazidpreventivetherapy criteriabeforeattendingthepulmonologyoutpatientclinic(OR:62.3;26.6–146.2),negative HIVinfectionstatus(OR:9.44;1.16–76.3);contactwithpulmonarytuberculosis(OR:5.57; 1.99–15.5),andresidinginRiodeJaneirocity(OR:1.89;1.04–3.44).

Conclusion:Strategiesthatincreaselatenttuberculosisinfectionidentiﬁcationandisoniazid preventivetherapyprescriptioninprimaryandsecondaryhealthunitsareurgentlyneeded. ©2015ElsevierEditoraLtda.Allrightsreserved.

∗ _{Corresponding}_author_at:_Rua_Sidnei_Vasconcelos_de_Aguiar,_222/casa18,_Glória,_Macaé,_RJ,_CEP:_27937-010,_Brazil. E-mailaddress:angelamcm@uol.com.br(A.M.C.Mendonc¸a).

http://dx.doi.org/10.1016/j.bjid.2014.12.005

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Introduction

Tuberculosis(TB)affects8.8millionpeopleeveryyear.1_It_is

estimatedthat10–15%ofthesecasesoccurinchildrenand adolescentsunder15years ofage. Thispercentageismost likelyhigherduetounderreportingofTBinthisagegroup.2

LatentTBinfection(LTBI)isestimatedtoaffectonethird oftheworldpopulation.1ChildhoodLTBIusuallyarisesfrom contactwithadultpulmonaryTB(PTB)patients.3

Approximately 5–10% of individuals with LTBI may progresstoactiveTBthroughoutlife,andthisprogressionmay reach40%inyoungerchildren.4,5_Isoniazid_preventive_therapy

(IPT)inthisagegroupreducesthelikelihoodofdisease pro-gressiontolessthan0.5%.5_Worldwide,_identifying_contacts_of

adultswithPTBandtreatingLTBIisconsideredapriority.1

Inmostcases,LTBIprogressesalmostimperceptiblyfrom the clinical point of view and can be confused with viral orbacterialinfectionswhensymptomatic,especiallyamong childrenandadolescents.Reactivitytothetuberculinskintest (TST)combinedwithexclusionofactiveTB6 _is_required_for

LTBIdiagnosis.

RecentguidelinesoftheInternationalUnionAgainst Tuber-culosisandLungDisease(IUATLD)inpartnershipwithother institutions encourage strategies for the care and training qualiﬁcationofPrimaryHealthCare(PHC)professionals, con-sideredtheindividuals’gatewaytohealthcare.Expandingthe investigationofLTBIandactiveTBinchildrenanddirecting asymptomaticchildofPTBcontactstoIPTatthishealthcare levelisrecommended.7

However,intheliterature,dataontheeffectivenessofsuch actionsinthePHCsofcountrieswithhighTBburden,suchas Brazil,arescarce.8–13

Operationalanalysesindevelopingcountriesshowedthat lessthanaquarterofthepediatricpopulationeligibleforIPT receivedit,showingadevaluationofthispreventivemeasure forchildhoodTB,particularlybyhealthcareprofessionals.13

Durovni8 _reported_that _only_18.4%_of_PTB _contacts_were

examined inashantytown inRio deJaneiro/Brazilin 2011 where100% ofthe community was visited bylocal health careworkers,andnoinformationwasavailableregardingIPT implementation.

This study aims to describe the investigation of LTBI withsubsequentIPTindicationinchildrenandadolescents attended in a reference hospital in Rio de Janeiro/Brazil, mostly coming from primary and secondary health units (HUs).

Study

population

and

methods

This is a descriptive, longitudinal and retrospective study conducted at the pulmonology outpatient clinic (POC) of the Jesus Municipal Hospital (Hospital Municipal Jesus – HMJ), located in the neighborhood of Vila Isabel, Rio de Janeiro/Brazil,from January2002toDecember 2009.HMJ is an exclusively pediatric HU, a municipal reference for the investigation and treatment of LTBI and TBeither associ-atedornotwiththehumanimmunodeﬁciencyvirus(HIV)in patientsunder15yearsofage.ThePOCreceiveschildrenand

adolescents from the pediatricdepartment and fromother specialtydepartmentsofthehospitalorreferredfromexternal HUs.

ThisstudywasapprovedbytheEthicsandResearch Com-mittee of the Clementino Fraga Filho University Hospital (HospitalUniversitárioClementinoFragaFilho–HUCFF)under researchprotocolnumber068/11CAAE.

Allchildrenunder15yearsofagewithLTBIreferredforIPT inthePOCandlivinginthestateofRiodeJaneiro/Brazilwere includedinthestudy,andnoindividualswereexcluded.Data were obtainedfromthemedicalrecordsofindividualswho receivedIPTinthePOC.

ConsideringtheoriginofindividualsreferredtothePOC, thefollowingstudygroupswereformed:

• Group1(G1):referredfromprimaryandsecondaryHUs. • Group2(G2):referredfromtheHMJgeneralpediatric

out-patientclinic.

• Group3(G3):referredfrom otherHMJ pediatricspecialty outpatientclinics.

Theindividuals studied were evaluatedattwo different times:atthefirstvisittothePOCandatthefollow-up,when the indicationforIPTwasdefined.ActiveTBwasexcluded onclinicalandepidemiologicalgrounds,clinicalexamination, chestradiography,and,whenindicatedandfeasible,gastric lavage fluid and/orinduced sputum examinationby Ziehl-Neelsenandcultureformycobacteria.TheBrazilianscoring systemrecommendedforchildhoodofPTB14_was_applied_to

theseindividuals.

Socio-demographic, clinical, radiological,and laboratory variableswererecordedinaformspeciﬁcallydesignedforthe study.

Atthetimeofthestudy,IPTwasindicatedaccordingtothe guidelinesoftheBrazilianMinistryofHealth(Ministérioda Saúde–MS)14_for_children_and_adolescents_under₁₅_years_of

agewithnosignscompatiblewithactiveTB.

TherewasindicationforrepeatingTSTafter8–12weeks in childrenand adolescents with initialTST<10mm. Indi-vidualswithtuberculinskintestconversion(TSTC),deﬁned asanincrease ofatleast10mmcomparedtothe previous TST,wouldalsobereferredforIPTafterexclusionofactive TB.14

Thedatacollectionformwasdevelopedusingthesoftware Access 1998,wherethe database wasstored. Theanalyses wereperformedusingthesoftwareStatisticalPackageforthe SocialSciencesversion17.0forWindows.Thevariables stud-iedweretestedforassociationwiththeexternaloriginofthe individuals.Thesigniﬁcancelevelwassetatp<0.05.The chi-squaretest,orFisher’sexacttestwhenindicated,wereusedto examineassociations.Logisticregressiontechniqueswerenot indicated,assomevariablescreatedduplicationinstatistical analysis.

Results

Intotal, 286childrenand adolescentswere includedinthe study. They had been referred to the POC with suspected activeTBor LTBIduetobeing contactsofadultswith PTB

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Table1–Distributionofclinicalandepidemiologicalcharacteristicsaccordingtostudygroupsin286individualsatthe ﬁrstvisittothePPOC.HMJ-RJ,2002–2009.

Variable G1 G2 G3 n169(%) n56(%) n61(%) Gender Female 81(47.9) 29(51.8) 29(47.5) Male 88(52.1) 27(48.2) 32(52.5) Agegroups

Children(<10yearsofage) 148(87.6) 49(87.5) 51(83.6) Adolescents(≥10yearsofage) 21(12.4) 7(12.5) 10(16.4)

Placeofresidence

CityofRiodeJaneiro 144(85.2) 42(75) 46(75.4)

StateofRiodeJaneiro 25(14.8) 14(25) 15(24.6)

CriteriaforIPTbeforeattendingatthePPOC

Yes 135(79.8) 3(5.4) 4(6.6) No 34(20.2) 53(94.6) 57(93.4) Weight,percentiles ≥10 161(95.3) 53(94.6) 55(90.2) <10 8(4.7) 3(5.4) 6(9.8) BCGvaccinationa Yes 148(100) 48(98) 57(100) No – 1(2) – NA 21 7 4

Tuberculinskintest(mm)b

≥10 164(100) 14(50) 7(35) <10 – 14(50) 13(65) NA 5 28 41 Presenceofsymptoms Yes 29(17.2) 24(42.9) 15(24.6) No 140(82.8) 32(57.1) 46(75.4)

ContactwithpulmonaryTB

Present 164(97) 51(91.1) 49(80.3)

Absent 5(3) 5(8.9) 12(19.7)

G1,individualsreferredfromexternalprimaryandsecondaryHUs;G2,individualsreferredfromtheHMJgeneralpediatricoutpatientclinic;

G3,individualsreferredfromotherHMJpediatricspecialtyoutpatientclinics;HMJ,JesusMunicipalHospital;NA,notavailable;PPOC,pediatric

pulmonologyoutpatientclinic;TB,tuberculosis.

a _n₌_254. b _n₌_212.

or not, symptomatic or not, and reactive or not to TST. All were diagnosed with LTBI and indicated forIPT atthe POC.

The individuals were distributed among the following groups: G1,169 (59.1%); G2, 56 (19.6%); and G3,61 (21.3%). Table1shows theclinical andepidemiological characteris-ticsofeachgroupattheirﬁrstvisittothePOC.G1showed greaterproportionofindividualswithLTBIdiagnosisreferred tothe POCwith noprescription ofIPTatthe place of ori-gin(135,79.8%),fromthecityofRiodeJaneiro(144,85.2%), with TST≥10mm (164; 100%), who reported contact with PTB (164; 97%), and who exhibited fewer symptoms (29; 17.1%).

AttheﬁrstvisittothePOC,wheninvestigatingsuspected casesofLTBIoractiveTB,aTSTwasrequestedfor74 individ-ualswhowerenottestedbeforecomingtotheunit,aiming to complement the investigation. Among the 286 individ-uals analyzed, 272(95%) were tested. Ofthese individuals, 212 (74.1%)had been tested before their ﬁrst visit toHMJ,

and 60 (21%) were tested after their ﬁrst visit. Regarding the TSTresult, 78%ofindividuals had induration≥10mm; 6%≥5–10mm;and11%<5mm.

ReactivitytoTST<10mmatthetimeofindicationforIPT atthePOCwasseenin49(17%)patients.Ofthesepatients,26 (53%)underwentanewTST(within6–8weeks)tosearchfor tuberculin contagiosum(TC),whichoccurred in19/26(73%) cases.

The68(24%)individualswhoweresymptomaticattheﬁrst visitwerefollowed-upuntilcompleteresolutionofsymptoms, atwhichtime IPTwasindicated.Antimicrobialdrugs were prescribedto58(85%)ofthem.Themostfrequentdiagnoses were pneumonia in31 (53%), and sinusitis in15 (26%). All individualsunderwentchestradiography.Abnormalities com-patiblewithlowerrespiratorytractinfectionswerefoundin27 (39.7%)symptomaticindividuals.Theseindividualsexhibited furthernormalcontrolradiologicalexamination,someafter appropriateantimicrobialtreatment,atwhichtimeIPTwas begun.

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Table2–Distributionofclinicalandepidemiologicalcharacteristicsaccordingtointernalandexternaloriginofthe286 individualsreferredtothePPOC.HMJ-RJ,2002–2009.

Variable Externalorigin

n169(%)

Internalorigin

n117(%)

Oddsratio(OR) (95%CI) p-Value Gender Female 81(47.9) 58(49.6) 0.93(0.58–1.50) 0.78 Male 88(52.1) 59(50.4) Agegroups <10yearsofage 148(87.6) 100(85.5) 1.19(0.60–2.38) 0.60 ≥10yearsofage 21(12.4) 17(14.5) Placeofresidence

RiodeJaneiroCity 144(85.2) 88(75.2) 1.89(1.04–3.44) 0.03 RiodeJaneiroState 25(14.8) 29(24.8)

CriteriaforIPTbeforeattendingthePPOC

Yes 135(79.8) 7(5.9) 62.3(26.6–146.2) 0.000 No 34(20.2) 110(94.1) Weight,percentiles ≥10 161(95.3) 108(92.3) 1.67(0.62–4.48) 0.29 <10 8(4.7) 9(7.7) BCGvaccinationa Yes 148(100) 105(99.1) 0.41 No – 1(0.9) NA 21 11

Tuberculinskintest(mm)b

≥10 164(100) 21(43.8) 0.001

<10 – 27(56.3)

NA 5 69

Presenceofsymptomsatﬁrstconsultation

Yes 29(17.2) 39(33.3) 0.41(0.23–0.72) 0.002

No 140(82.8) 78(66.7)

ContactwithpulmonaryTB

Present 164(97) 100(85.5) 5.57(1.99–15.5) 0.000 Absent 5(3) 17(14.5) HIVserostatusc Negative 20(95.2) 36(67.9) 9.44(1.16–76.3) 0.03 Positive 1(4.8) 17(32.1) NA 148 64

HIV,humanimmunodeﬁciencyvirus;HMJ,JesusMunicipalHospital;NA,notavailable;PPOC,pediatricpulmonologyoutpatientclinic;TB,

tuberculosis.

a _n₌_254. b _n₌_272. c _n₌_74.

Amongthe286individualsstudied,18/230(7.8%)already exhibitedpositiveserologyforHIVintheirﬁrstvisittothePOC. ThepresenceofHIVwassearchedforin56/268individuals with unknown HIV serostatus, and all results were nega-tive.

Thecomparativeanalysisbetweenindividualswith exter-nal (G1) and internal origin (G2 and G3), according to clinical and epidemiologicalcharacteristics, isdescribed in Table2.

Inthe univariateanalysis, a signiﬁcant association was observedbetweenexternalorigin(HUs)andthefollowing fac-tors:residenceinthecityofRiodeJaneiro(p=0.03);presence ofLTBcriteriawithnoIPT(p=0.000);positiveTST(p=0.001); lowerproportionofsymptomsatﬁrstvisit(p=0.002);history ofcontactwithPTB (p=0.000);and HIV-negative serostatus (p=0.03).

Discussion

This study analyzedindividuals referred tothe POC atCH withpresumedTB/LTBI.Attheﬁrstvisit,approximatelyhalf ofthecaseshadpreviouslyestablishedcriteriaforLTBI diag-nosis and indication for IPT (history of contact with PTB, TST≥10mm,absenceofsymptoms)accordingtotheNational Brazilian Guidelines.14 _{Additionally,} _80% _(135/169) _of _those

referredfromprimaryandsecondaryHUs(G1)presentedwith criteriaforanLTBIdiagnosis,andIPTwasnotindicatedatthat level.

Inourstudy,therewasasigniﬁcantassociationbetween externalorigin(G1)andnegativeHIVinfectionstatus.Wecan speculatethatHIV-infectedpatientsreceivedIPTatthe pri-maryand secondary HUs fasterthan patients notinfected

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withHIV due togreater disseminationto health care pro-fessionals of guidelines for LTBI diagnosis in HIV-infected patients.Itisnoteworthythatalmostallindividualsinfected withHIV were referred from other HMJ clinics tothe POC forIPTprescription,evenafteractiveTBwasruledout, con-ﬁrmingthedifﬁcultyfacedbythehealthcareprofessionals, eveninpediatrichospitals,inrulingout TBforsubsequent IPTprescription.4,14

In Brazil, we found no information in the literature regardingthereferralofchildrenandadolescentsfromPHC units to reference units in relation to LTBI diagnosis and indication for IPT. Similar to the reports of Banu Rekha et al.15 _and _Tornee _et _al.16 _in _India _and _Thailand,

respec-tively, weassume that inour study,the factors associated with no indication for IPT in the population that came from primary and secondary HUs may be related to the following: limited acceptance or ignorance of the impor-tance of IPT by health care professionals, ignorance of standard diagnostic criteria for LTBI by prescribing physi-cians, and loweffectivenessof measuresforTBcontrol in childrenand adolescents in theseHUs. Thislow effective-ness could also be related to the fact that children have a history ofbeing neglected regarding TB control because they contribute only minimally to spreading TB in the community.17

Moreover,wecannotruleoutthescarcityofresourcesfor performingTSTandchestradiographyinsomeprimaryand secondary HUs,which could explainthe low resolution in pediatriccasesofsuspectedactiveTBforrulingoutTBand startingIPT.8,9_The_lack_of_trained_human_resources_in

child-hoodTBinprimaryandsecondaryHUsinRiodeJaneirocould alsobeoneofthereasonsfordifficultiesininitiatingIPTin this population, asmostchildren and adolescents referred fromthoseunitstothePOChadnosymptomsthatjustifieda thoroughevaluationforactiveTBanddifficultyinprescribing IPT.

In studies with Asian children, without specifying the healthcarelevelwheretheywere conducted,doctorscited insufficientdissemination of guidelines for LTBI diagnosis, difficulties ofthe health system in implementing IPT, and fearofcreatingunnecessary adverseeffects asreasons for deficientIPT prescription.15,16 _In _Malawi,_the _barriers _cited

were:lack ofmaterialsto performTST;lack ofequipment toperform chest radiography;lack oftrained personnel to interpretthetestresults;andhigh workloadofhealthcare professionals under poor working conditions18_. _In

Indone-sia, the caregivers of child and adolescent PTB contacts who underwent screeningfor activeTB faced obstacles to thescreeningprocessbecausetheyencountereddifﬁculties in arriving at the HU due to transportation expenses and lost workdays.Thisway,92% oftheeligiblechild and ado-lescent contacts for LTBI/active TB were lost after initial evaluation.19

Inastudy inSalvador state,Brazil,Monroeet al.20 _also

found that primaryand secondary health care profession-alswereinsufﬁcientlytrainedforTBcontrol,overloadedwith work,andminimallysupervised,resultinginnoncompliance withNationalBrazilianGuidelinesformanagingthedisease. IntheRocinhashantytownofRiodeJaneiroin2011,whichhad high primaryhealthcoverage,Durovni8 _reported_that _after

100%ofthe communitywasvisited bylocalhealth profes-sionals,only18.4%ofclosecontactswerescreenedforLTBI. Recently,inanotherstudyconductedinthesameshantytown ofRiodeJaneiro,Machado21_reported_the_difﬁculty_in

track-ingchildcontactsofpatientswithPT(children’sdailycontact networkisnotlimitedtotheresidentsofahousehold,and healthcareprofessionalscannotensuresecurityinworking withchildren).Theauthorsalsoreportthatfamilyphysicians (who arenotspecialists andare focusedontheadult pop-ulation) exhibited difﬁculties in dealing with children and considered themtheresponsibilityofthepediatric special-ist.Conversely,inanoperationalstudyconductedinRiode Janeiro,Durovnietal.,10_in_a_cluster_randomized_trial,_reported

asigniﬁcant increaseinIPTprescriptionsin29 PHCclinics for the care ofHIV-infected individuals after TBscreening training,witha24%decreaseindeathsfromTBinthis popu-lation.

Overall,thedeﬁciencyofresourcesforbetterLTBIscreening inchildrenandadolescentsinprimaryandsecondaryHUshas notbeenevaluatedinBrazil,butapoorresolutionatthe pri-marycarelevelinthediagnosisofadultpresumedTBpatients attendedinﬁvemunicipalitieshasbeenhighlightedbyVilla etal.22

TheWHOemphasizesthateveninplaceswithextremely limited resources, where TST and chest radiography are not available, there is no justiﬁcation for not prescribing treatmentforactiveTBorLTBIinchildandadolescent con-tacts of adultswith PT. Currently, in these situations, the WHOrecommendsthescreeningapproachbasedon symp-toms associatedwith activeTB.3,21 _Asymptomatic _children

are directly eligible forIPT, whereas symptomaticchildren requirefurtherinvestigationtoruleoutactiveTBbeforeIPTis started.3

Aslimitationsofthisstudy,wenotethatthepopulation studiedincludedonlychildrenandadolescentstreatedatHMJ. Therefore,thestudydoesnotallowinferencesregardingall patientswithLTBIintheagerangestudiedwhoresideinthe stateofRiodeJaneiro.Furthermore,thisstudyhaslimitations inherenttostudiesthatuseasecondarydatasource,dueto theincompletenessofbasicinformation.

StrategiestoincorporatechildhoodTB/LTBIinPHCshould beencouraged,andprospectiveoperationalresearchstudies should be performed with this population. Further stud-ies should be conducted to validate our results, and new approaches that include qualitative evaluation of health servicesshouldbeprioritizedtoidentifyhinderingand facil-itatingfactorsfortheimplementationofIPTinprimaryand secondaryHUsincountrieswithhighTBburdens.

Conﬂicts

of

interest

Theauthorsdeclarenoconﬂictsofinterest.

Acknowledgements

Theauthorswould liketothanktheHMJstaff andDaniela Ramalhoforthestatisticalanalysis.

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