Determinants of Default from Tuberculosis Treatment among Patients with Drug-Susceptible

14 Pages·2015·0.22 MB·English

RESEARCHARTICLE
Determinants of Default from Tuberculosis
Treatment among Patients with Drug-
Susceptible Tuberculosis in Karachi, Pakistan:
A Mixed Methods Study
NatashaChida1,2*,ZaraAnsari3,HamidahHussain4,MariaJaswal4,StephenSymes1,
AamirJ.Khan3,4,ShamaMohammed3
1 JayWeissInstituteforHealthEquityatSylvesterComprehensiveCancerCenter,UniversityofMiamiMiller
SchoolofMedicine,Miami,Florida,UnitedStatesofAmerica,2 DepartmentofInternalMedicine,Divisionof
InfectiousDiseases,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland,UnitedStatesof
America,3 InteractiveResearchandDevelopment,Karachi,Sindh,Pakistan,4 IndusHospitalResearch
Center,IndusHospital,Karachi,Sindh,Pakistan
*[email protected]
OPENACCESS
Abstract
Citation:ChidaN,AnsariZ,HussainH,JaswalM,
SymesS,KhanAJ,etal.(2015)Determinantsof
DefaultfromTuberculosisTreatmentamongPatients
withDrug-SusceptibleTuberculosisinKarachi, Purpose
Pakistan:AMixedMethodsStudy.PLoSONE10(11):
Non-adherencetotuberculosistherapycanleadtodrugresistance,prolongedinfectious-
e0142384.doi:10.1371/journal.pone.0142384
ness,anddeath;therefore,understandingwhatcausestreatmentdefaultisimportant.Paki-
Editor:José-MaríaGarcía-García,HospitalSan
stanhasoneofthehighestburdensoftuberculosisintheworld,yettherehavebeenno
Agustín.Aviles.Asturias.Spain,SPAIN
qualitativestudiesinPakistanthathavespecificallyexaminedwhydefaultoccurs.Wecon-
Received:March29,2015
ductedamixedmethodsstudyatatuberculosisclinicinKarachitounderstandwhypatients
Accepted:October21,2015 withdrug-susceptibletuberculosisdefaultfromtreatment,andtoidentifyfactorsassociated
Published:November12,2015 withdefault.Patientsattendingthisclinicpickupmedicationsweeklyandundergofamily-
supporteddirectlyobservedtherapy.
Copyright:©2015Chidaetal.Thisisanopen
accessarticledistributedunderthetermsofthe
CreativeCommonsAttributionLicense,whichpermits Methods
unrestricteduse,distribution,andreproductioninany
medium,providedtheoriginalauthorandsourceare In-depthinterviewswereadministeredto21patientswhohaddefaulted.Wealsocompared
credited. patientswhodefaultedwiththosewhowerecured,hadcompleted,orhadfailedtreatment
DataAvailabilityStatement:Allrelevantquantitative in2013.
dataarewithinthepaperanditsSupporting
Informationfile.Regardingourqualitativedata,our Results
participantsdidnotconsenttohavetheirfull
transcriptsmadeavailable.However,theydid Qualitativeanalysesshowedthemostcommonreasonsfordefaultwerethefinancialbur-
consenttohavingexcerptsoftheirtranscriptsmade denoftreatment,andmedicationsideeffectsandbeliefs.Theinfluenceoffinanceson
available.Therefore,duetoethicalrestrictions,
othercausesofdefaultwasalsoprominent,aswasconcernabouttheeffectoftreatmenton
excerptsarepresentwithinthemanuscript,butif
familymembers.Inquantitativeanalysis,of2120patients,301(14.2%)defaulted.Univari-
furtherexcerptsarerequested,pleasecontact
[email protected]. ateanalysisfoundthatmalegender(OR:1.34,95%CI:1.04–1.71),being35–59yearsof
age(OR:1.54,95%CI:1.14–2.08),orbeing60yearsofageorolder(OR:1.84,95%CI:
Funding:Thisworkwassupportedbyaninternal
grantfromtheJayWeissInstituteforHealthEquityat 1.17–2.88)wereassociatedwithdefault.Afteradjustingforgender,diseasesite,and
PLOSONE|DOI:10.1371/journal.pone.0142384 November12,2015 1/14
DefaultfromTuberculosisTreatmentinKarachi,Pakistan
SylvesterComprehensiveCancerCenter,atthe patientcategory,being35–59yearsofage(aOR:1.49,95%CI:1.10–2.03)or60yearsof
UniversityofMiamiMillerSchoolofMedicine.NC ageorolder(aOR:1.76,95%CI:1.12–2.77)wereassociatedwithdefault.
receivedfundingasaSocialMedicineandHealth
EquityInternalMedicineResidentattheUniversityof
Conclusions
MiamiMillerSchoolofMedicine.Thereisnogrant
numberforthisinternalaward.TheJayWeiss Inmultivariateanalysisagewastheonlyvariableassociatedwithdefault.Thislackofidenti-
Institutehadnoroleinstudydesign,datacollection
fiableriskfactorsandourqualitativefindingsimplythatdefaultiscomplexandoftendueto
andanalysis,decisiontopublish,orpreparationof
themanuscript.Funder'surl:http://sylvester.org/jw. extrinsicandmedication-relatedfactors.Moretolerablemedications,improvedsideeffect
management,andinnovativecost-reductionmeasuresareneededtoreducedefaultfrom
CompetingInterests:Theauthorshavedeclared
thatnocompetinginterestsexist. tuberculosistreatment.
Introduction
Pakistanisoneofthehighest-burdentuberculosis(TB)countriesintheworld,withanannual
caseincidenceof500,000[1].ThePakistanNationalTuberculosisProgramreporteduniversal
directlyobservedtherapy(DOT)coverageinthepublicsectorin2005,andrecentlybegan
implementingpublic-privatemodelsofcaretoimprovecasedetection[2,3].Despitethese
accomplishmentsTBcontinuestobeasignificantpublichealththreat;Pakistanhasbecomea
high-burdenmultidrugresistant-TB(MDR-TB)country,andin2013accountedfor80%ofthe
WorldHealthOrganizationEasternMediterraneanRegion'sMDR-TBburden[1].
Non-adherencetoTBtherapycanleadtodrugresistance,prolongedinfectiousness,and
death[4].ThePakistanNationalTuberculosisProgramestimatesthedefaultratefornewcases
tobelessthan4%,butrecentstudieshavefoundratesbetween7–16%[2,3,5–8].Defaultis
influencedbyfactorsthatvarybygeographiclocation,suchaseconomicsandhealthbeliefs;
therefore,successfulinterventionsrequireanawarenessoflocalcontexts[9–11].Inaddition,
understandingtheeffectsofbeliefsontreatmentbehaviorisnecessarytofullyevaluatedefault
[12].Whilequantitativeresearchishelpfulforidentifyingriskfactorsfordefault,itisunableto
completelyinvestigatepatients’reasonsforleavingcare.Theadditionofqualitativedataisnec-
essaryforin-depthevaluationsofdefaultinTBprograms,yetmuchoftheexistingstudieson
defaulthavenotincludedqualitativeanalyses[4].Forexample,inPakistantherehavebeenno
qualitativestudiesspecificallyexaminingwhypatientsdefault;threepreviouslypublishedstud-
iesdidincludesmallsub-groupsofdefaultersaspartsoflargerwork,buttheprimaryobjective
ofthesestudieswasnottoidentifyreasonsfordefault[13–15].
Thisstudywasconductedtodeterminewhypatientswithdrug-susceptibleTBinKarachi
defaultfromTBtreatment,andtoidentifypatientfactorsassociatedwithdefault.Weachieved
theseaimsbyperformingaretrospectiveanalysisoftheIndusHospitalTBClinic’spatient
database,andbyadministeringin-depthinterviewstopatientswhohadpreviouslydefaulted.
MaterialsandMethods
Ethicalconsiderations
Theinstitutionalreviewboards(IRB)ofInteractiveResearchandDevelopment,Karachi,Paki-
stan,andtheUniversityofMiamiMillerSchoolofMedicine,Miami,UnitedStateseach
approvedthestudy.
Studysettingandpopulation
ThestudyinvolvedparticipantswhohadattendedtheoutpatientTBclinicoftheIndusHospi-
tal,afree-of-charge150-bedfacilitylocatedinalow-incomeindustrialareaofKarachi.Over
20millionpeopleliveinKarachi;manyaremigrantworkersfromvariedethnicbackgrounds
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DefaultfromTuberculosisTreatmentinKarachi,Pakistan
[6].IndusHospital'scatchmentpopulationconsistsof2.5millionpeople,andapproximately
350patientsareseenintheTBcliniceachday[16].TheIndusHospitalhasonetreatmentpro-
gramforpatientswithdrug-susceptibleTBandanotherforpatientswithdrug-resistantTB.
Thisstudyevaluatedpatientsinthedrug-susceptibleprogram.Drugresistanceisdetermined
1
whenpatientspresenttoclinicforthefirsttimebyuseoftheGeneXpert MTB/Riftest;if
rifampinresistanceisdetected,patientsundergodrug-susceptibilitytesting.
Patientswithdrug-susceptibleTBaretreatedperguidelinesfromthePakistanNationalTB
ControlProgram[17].Thosewhoarebeingtreatedforthefirsttime(Category1)receive2
monthsofisoniazid,rifampin,pyrazinamide,andethambutol,and4monthsofisoniazidand
rifampin.PatientswhotransferintotheIndusprogramfromanotherfacilitywhileontherapy
arealsoconsideredCategory1.Patientswhoareexperiencingre-treatment(Category2)
receiveof2monthsofisoniazid,rifampin,pyrazinamide,ethambutol,andstreptomycin;1
monthofisoniazid,rifampin,pyrazinamide,andethambutol;and5monthsofisoniazid,
rifampin,andethambutol[17].Patientspickupmedicationsfromtheclinicweeklyand
undergodailyfamily-supportedDOT.TheTBclinickeepsadatabaseofcontactinformation
forpatientswhoaretreatedattheclinic.Whenpatientsinitiatecaretheyareaskediftheycon-
senttobecontactedforresearchpurposesinthefuture;thosewhodonotconsentcannotbe
contactedforresearch.
Qualitativedatacollection
Afemalestudymembertrainedinqualitativemethodsconductedsemi-structuredin-depth
interviewswithadultpatients(ages18andolder)whohaddefaultedfromTBtreatment.This
studymemberwasnotinvolvedwithclinicalcareattheIndusHospital.In-depthinterviews
werechosenasthemethodofdatacollectionduetothesensitiveandcomplexnatureofrea-
sonsfordefault.Theinterviewfocusedonreasonsfordefaulting,butalsocontainedcues
relatedtohealthexperiences,relationships,TBbeliefs,andfinances(Table1);theinterview
waspilotedwith5volunteerclinicpatientspriortoimplementation.
Qualitativestudyparticipantswererecruitedbytelephone;usingtheTBclinic'sdatabaseof
patients,thestudymemberidentifiedpatientswhohaddefaultedsincetheclinicopenedin
2007.Outofthe632patientsidentifiedasdefaultersinthedatabasebetween2007and2013,
contactinformationwasavailablefor331.Wethensoughttoemployamaximumvariation
samplingstrategybasedondemographicvariables,buthaddifficultytracingthepatients[18].
Wesubsequentlyattemptedtocontactall331patientsandwereabletosuccessfullytrace42
people.Twoagreedtoparticipate,whiletherestrefused.Themostcommonreasonsforrefusal
citedbypatientswerenotbelievingtheyeverhadTB,feelingbetter,andbeingconcerned
abouttheircommunityfindingouttheyhadbeentreatedforTB.
Table1. Examplesofin-depthinterviewquestions(Englishtranslations).
PleasetellmewhatyouknowaboutTB.
CanyoutellmewhyyouwereunabletocompletetreatmentatIndus?
CanyoudescribewhatyouroverallexperiencegettingtreatmentatInduswaslike?
NowIwantyoutothinkbacktothetimeyoustoppedgoingtoIndusforTBtreatment.Tellmewhat
happenedandwhatyoudid.
CanyoudescribeyourrelationshipswithyourfamilyafteryouwerediagnosedwithTB?
CanyoudescribeyourrelationshipswithyourneighborhoodafteryouwerediagnosedwithTB?
TB=tuberculosis
doi:10.1371/journal.pone.0142384.t001
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WesubsequentlyobtainedIRBapprovaltoperformtelephoneinterviewsandre-calledall
ofthepatientswhohadpreviouslynotansweredorrefusedtoparticipate.19patientsagreedto
beinterviewed;wethereforeconducted2in-personand19telephoneinterviewswith10men
and11women.Duringoneinterviewapatientstatedshehadtransferredhercaretoanother
facilityandhadnotdefaulted;herinterviewwasthereforenotanalyzed.Weintendedtouse
saturationtodetermineoursamplesize,butduetoourdifficultywithtracingpatientsthiswas
notpossible.Ofnote,thepatientswewereattemptingtocontacthaddefaultedbetween2007
and2013;however,ofthe21whoagreedtobeinterviewed19happenedtohavedefaultedin
2013,while2haddefaultedin2012.
AllinterviewswereconductedinUrdu(thenationallanguageofPakistan)andtookplace
betweenJuneandAugustof2014.Boththeparticipantsandthestudymemberwerealonedur-
ingtheinterviews.Priortoeachinterviewtheparticipantswereinformedofthereasonforthe
studyandverbalinformedconsentwasobtained;anIRB-approvedoralconsentscriptwas
used,anddocumentationofconsentwasrecordedonthescript.Astheinterviewsoccurredvia
telephone,writteninformedconsentwasnotpossible.Interviewswereaudiorecordedintheir
entirety,transcribedverbatimintoUrdu,andsubsequentlytranslatedintoEnglish;tomaintain
anonymityparticipantnameswerenotincludedontranscriptions.Themediantimetocom-
pletetheinterviewwasapproximately30minutes.
Quantitativedatacollection
Thestudypopulationincludedallpatientsinthedrug-susceptibleTBprogramwhohadatreat-
mentoutcomein2013.Treatmentoutcomesincludedthefollowing:“treatmentcure,”“treat-
mentfailure,”“treatmentcompletion,”“died,”“defaulted,”“changeindiagnosis,”or“transferred
caretoanotherTBprogram.”ThedefinitionsoftheseoutcomeswerederivedfromWorldHealth
OrganizationandPakistaniguidelines[1,17].Treatmentcurewasdefinedashavingconfirmed
TBandbeingsmearorculture-negativeatboththeendoftreatmentandonatleastoneprior
occasion.Duetothedefinitionrequiringasmearorcultureresultattheendoftherapy,whichis
difficulttoobtaininpatientswithextrapulmonaryTB,onlypulmonaryTBpatientscouldbeclas-
sifiedascured.TreatmentfailurewasdefinedaseitherapatientwithpulmonaryTBhavinga
positivesmearorcultureresultat5monthsoftreatmentorlater,orapatientwithextrapulmon-
aryTBhavingapoorclinicalresponseat5monthsoftreatmentorlater.InpulmonaryTB
patients,treatmentcompletionwasdefinedascompletingtherapywithoutevidenceoftreatment
failure,andnothavingrecordofanegativesmearorcultureresultatboththeendoftherapyand
ononeprioroccasion.InextrapulmonaryTBpatients,treatmentcompletionwasdefinedassuc-
cessfullycompleting6–8monthsoftreatment.Bothtreatmentcureandtreatmentcompletion
wereconsideredsuccessfultreatmentoutcomes.Defaultwasdefinedasstartingtherapyandhav-
ingatreatmentinterruptionof2ormoreconsecutivemonths.
Patientswhowereactivelyreceivingtreatmentduringthestudyperiod(thatis,hadnot
completedastandard6–8monthcourseoftherapyandthereforedidnothaveatreatmentout-
come)werenotpartofthestudypopulation.Welimitedtheanalysisto2013becausethiswas
theyearthemajorityofourqualitativestudypatientslefttreatment.Patientdemographicsand
clinicaloutcomeswereabstractedfromtheTBclinic’spatientdatabase(S1Dataset).Ourpri-
maryoutcomewasdefaultstatus,whichwasdefinedasatreatmentinterruptionof2ormore
consecutivemonths[1].
Qualitativedataanalysis
Analysiswasundertakenbytheprimaryauthorusingthematicframeworkanalysis[18].After
apreliminaryreadingofthetranscripts,recurringthemeswereidentified.Inductivecodes
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DefaultfromTuberculosisTreatmentinKarachi,Pakistan
weredeveloped,andalltranscriptionswerecatalogedaccordingtothedefinedcodingsystem.
Thecodeswerethencompiledintolargercategoriesandthenoverallthemes.Oneadditional
studymembertrainedinqualitativemethodsindependentlyreviewedthecodingandcatego-
ries;disagreementswerereviewedandresolvedbyathirdstudymember.Theanalysiswas
donemanually.
Quantitativedataanalysis
Thedemographicandclinicalcharacteristicsofthestudypopulationwereevaluated.Wethen
performedbinarylogisticunivariateandmultivariateregressiontoassessfactorsassociated
withdefault.Patientsinthecohortwhodefaultedfromtreatmentwerecomparedtopatients
whohadnot.Patientswhodidnotdefaultwerethosewhocompletedastandard6–8month
courseoftreatment(regardlessofwhethertheywerecategorizedastreatmentcure,treatment
completion,ortreatmentfailure).Patientswhodied,transferredtheircaretoanotherfacility,
orhadachangeindiagnosiswereexcludedfromtheunivariateandmultivariateanalysis.Vari-
ablesintheunivariatemodelthathadap-valueof0.2orlesswereincludedinthemultivariate
model.Oddsratiosand95%confidenceintervalsforeachvariablewerecalculated,andp-val-
uesoflessthan0.05wereconsideredsignificant.DatawasanalyzedusingSPSSversion21.
Results
Qualitativeresults
Fivethemesregardingreasonsfordefaultemergedduringanalysis:thefinancialburdenof
treatment,medicationsideeffectsandbeliefs,TBbeliefs,healthsystemeffects,andtheeffectof
TBdiagnosisandtreatmentoninterpersonalrelationships.Thethemes,categories,andcodes
arepresentedinTable2;quotationsareusedtoillustratethecategories.
Priortostoppingtherapypatientscarefullyconsideredtheperceivedbenefitsandharmsof
treatment.Theirdecisiontoleavecarewasguidedbyspecificreasons,ratherthancasualdeci-
sion-making.Patientsreportedmajor,or"primary"reasonsfordefault,thennoted"secondary"
reasons(whichcontributedtotheirdefaultbutdidnotcauseit).Themostcommonlynoted
primaryreasonsfordefaultwerethefinancialburdenoftreatmentandmedicationsideeffects
andbeliefs;themostcommonsecondaryreasonwasfinancialburden.Mostpatientsalso
describedadditionalproblemsthatmadetreatmentdifficultbutdidnotdirectlycontributeto
theirdefault;themajorityoftheseproblemswererelatedtofinancesandissueswiththehealth
system.
Financialburden. Halfofthesamplereportedfinancesasaprimaryorsecondaryreason
fordefault,makingitthemostcommonthemereferencedoverall.Mostpatientswereprimarily
concernedaboutthefinancialburdenofthetreatmentontheirfamilies:
"Ihadnootherreasontoleavetheprogrambutthefinancialburdenitputonmyfamil-
y...myfatherusedtocomewithmetothedoctor,andwewouldtakearickshaw.Thecost
wouldalmostbea100rupeesforoneperson...200rupeesisalargesumforsomeonethat
makes4000rupeesamonth.Noonewillstoptakingmedicinesunnecessarily.Wedon’t
haveadeathwish."(femalepatient)
Allofthecostsnotedbypatientswereeitherindirectordirectnon-medicalcosts;forexam-
ple,themajorityofthepatients(regardlessofgender)wereaccompaniedtoclinic,andmany
reportedlostwagesforthemselvesortheiraccompagnateurduetolongclinicwaitingand
traveltimes.Overall,halfofthesamplereportedthattreatmentnegativelyaffectedtheiror
theirfamily'swork.
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Table2. Themeswithrelatedcategoriesandinductivecodes.
Themes Categories Codes
Financialburden Workeffects Missedworktogotoclinicandfiredorthreatenedwithbeing
fired
Couldnotworkduetosymptomsorsideeffects
Familymembermissedworktogotoclinic
Indirectcosts Costoftransportationtoclinic
Costoffoodsandadditionalmedicationstodecreaseside
effects
Treatmentcostspreventedfamilyfromobtainingfood,
schooling,otherneeds
Medicationsideeffectsandbeliefs Sideeffects Feltworseontreatment
Couldnotperformhouseholddutiesduetosideeffects
Pillswerelargeandpainfultoswallow
Decidedtotrytreatmentwithplanstostopifdidnotfeelbetter
soon
Medicationfailed Sideeffectsmeanttreatmentwasnotworking
Notfeelingbetterquicklymeanttreatmentwasnotworking
Medicationwasharmful Treatmentcausessterility
AmericanschangedTBmedicinetomakepatientssterile,like
poliovaccine
MedicinecausedmoreillnessthanTBdid
Medicinewasexpired
Medicationsuccess Feltbettersonofurthertreatmentrequired
Feltbettersocostoftreatmentwasanunnecessaryexpense
Feltbettersonot“worthit”toexperiencesideeffects
TBbeliefs ContingencyPlan Feltbetterandwillreturntocareifsymptomsrecur
Couldnotaffordtreatmentsowillreturntocareifsymptoms
becomesevere
Willwaituntilmoneyavailabletoreturntotreatment
Curability TBiscurableifonetakesmedicine
TBisnotcurableandislikecancer
TBiscurablebuttreatmentdidnotwork
Healthsystemeffects Negativeprovider Providerdidnotlistentoconcerns
interactions
Providerandclinicstaffwererude
Positiveprovider Providerandclinicstaffwerekindandrespectful
interactions
Providerwasgoodbutdidnotunderstandsideeffectseverity
Providerwasgoodbutunawaremedicationswereharmful
Healthcaretime Tooktoolongtotravelbetweenhomeandclinic
Clinicvisittookalldayandledtoworsesymptoms
Clinicvisittookfamilymembersawayfromworkfortoolong
Healthsystem AllgovernmenthospitalsandclinicsinPakistanarebad
dissatisfaction
ThegovernmentdoesnotcareaboutTBpatients
EffectofTBdiagnosisandtreatmentoninterpersonal Supportivehome Familywassupportiveandhelpful
relationships relationships
Familyateless/spentlessonthemselvessomorecouldbe
spentontreatment
Familyadministeredmedicationsandreinforcedadherence
(Continued)
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DefaultfromTuberculosisTreatmentinKarachi,Pakistan
Table2. (Continued)
Themes Categories Codes
Unsupportivehome Mother-in-lawcausedillnessandwasnotgivingthecorrect
relationships medicines
Mother-in-lawimpliedhavingTBdecreasedmasculinity
Husbandforcedtreatmentdiscontinuation
Community-basedstigma Friendsavoidedinteraction
Communitymembersgossipedandavoidedinteractions
TBdiagnosismustbehiddenfromthecommunity
Marriageability NoonewillmarrysomeonewithTB
NoonewillmarrytherelativesofsomeonewithTB
Guilt Unabletocontributetohouseholdduetoillness
Costoftreatmentwasaburdenonthehousehold
Familycouldsuffersocialstigma
TB=tuberculosis
doi:10.1371/journal.pone.0142384.t002
Financialconcernsalsoinfluencedpatients’experiencesofothercausesofdefault.Among
patientswhodefaultedduetomedicationsideeffects,gastrointestinalsymptomswerecom-
mon.Manyboughtspecialfoodsorover-thecountermedicationstoeasetheirsymptoms,
whichincreasedoverallcosts.Inaddition,patientsoftenreportedhavingtohiretaxisorrick-
shawstogettotheclinic,ratherthantakingpublictransportation;thiswasbecausetheyfelt
weakfromtheirTBinfection,medicationsideeffects,orboth:
"Ihadtotakeataxibackandforth(toclinic)becauseIwasweak...Apartfromthat,Ihad
topayfortheextramedicineItooktokeepmyselfhealthy...Ihadtothinktwiceabout
comingfortreatmentbecauseoftheextracostsassociatedwithit."(malepatient)
Medicationburdenandbeliefs. Medicationsideeffectswerethemostcommonly
reportedprimaryreasonfordefault.Whenpatientsdefaultedduetosideeffectsitwasbecause
theirsymptomsweresevereandmadethemfeelworsethantheirTB-relatedsymptomsdid:
"Icouldn’tsleepatnight.Everythingmademesickandnauseous...Everythingwasgoing
wrong...themedicationwasmakingmeworse.”(malepatient)
Somepatientsthoughttheirsideeffectsindicatedthemedicationshadeitherfailedorwere
harmful.TwomalepatientsstatedthatbothTBmedicationsandthepoliovaccinewerebeing
giventointentionallycausesterility:
"InthesamewaythattheAmericansinfiltratedusingthepoliomedicine,theystarteddoing
thesamewithTBmedicine...Icouldnottaketheriskofnothavingchildren."(male
patient)
Otherpatientsstoppedtherapybecausetheyfeltbetterandbelievedthismeanttheyhad
receivedenoughtreatment,orfeltthattheycouldnotjustifythecostoftreatmentwhentheir
symptomshadimproved.
TBbeliefs. Allbut3ofthepatientsbelievedTBwascurableandthoughttreatmentwas
beneficial;theyoftencreatedacontingencyplantoreturntocareiftheirhealthdeterioratedor
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iftheirprimaryreasonfordefaultresolved.Inaddition,theyoftenrealizedtheymightgetill
withTBinthefuturebecausetheyhadnotcompletedtreatment:
"IcametogetthemedicationtopushmyTBawayforafewyearssoIcansetupmylife.IfI
getsymptomsagainwecantakeitfromthere...Rightnowitwasjustnotsmartformeto
beapartoftheprogram.IjustoptedforthreemonthsoftreatmentthatIcouldafford...I
gotstrongerandIwasabletostartworking."(femalepatient)
The3patientswhodidnotbelieveTBwascurableheldthisconvictionpriortobecomingill
andhadseenfamilymembersdieofTB.Thesepatientsallcommentedtherewasnoreasonto
suffertheperceivedharmsofTBtreatment(costs,sideeffects,etc.),asitwouldnotcurethem.
Healthsystemeffects. Mostofthepatientsnotedgoodhealthproviderinteractions;how-
ever,despitethistheydidnotacceptprovidercounselingthatcontradictedtheirpreexisting
beliefsaboutTB:
"Thedoctorwasverynicetome...howeveritdidn’thelptakeawaymyfears.Iwascon-
vincedthatIhadgottenthis(TB)becauseofmymother-in-lawandthatitwasherfault."
(femalepatient)
Amongthe4patientswhodefaultedduetonegativeproviderinteractions,3weredissatis-
fiedwiththeentirePakistanihealthsystemandbelievedtherewasnoutilityseekingcare
elsewhere.
EffectofTBdiagnosisandtreatmentoninterpersonalrelationships. Themajorityof
patientshidtheirdiagnosesfromtheircommunitiesduetoconcernsaboutcommunity-based
stigma,butnonestatedthiswasareasonfordefault.Twomenand3womenwereconcerned
theirortheirfamilymembers'marriageabilitywoulddecreaseifthecommunityfoundoutthey
hadTB:
"HavingTBisahorrorstory.Whywouldanypersonwanttomarrytheirdaughterorson
intothatkindofanatmosphere?Whywouldtheywanttomarrymeorhaveapartinmy
familyifIhaveTBorAIDSforexample?"(malepatient)
Mostpatientshadsupportivehomerelationshipsbutwerehighlyconcernedaboutthe
impactoftheirtreatmentontheirfamilies;the4patientswhocitedguiltasaprimaryorsec-
ondaryreasonfordefaultallhadsupportivehomerelationships.Twopatientstoldtheirfami-
liestheywereleavingtreatmentduetosideeffectsorfeelingbetter,whentheyactuallywere
worriedaboutfinances:
"He(husband)usedtogetlessoftheotherfoodsohecouldgetmorefoodforme...Ialways
feltguilt...Itoldmyhusbandthesideeffectsweretoomuch,butthecostwasthemain
problem..."(femalepatient)
Ofthe3patientswhoprimarilyorsecondarilydefaultedduetounsupportivehomerela-
tionships,eachhadauniqueexperience.Onewomanstoppedtreatmentbecausehermother-
in-lawtreatedherpoorlyafterherdiagnosis,anotherstoppedbecauseherhusbanddemanded
it,andonemanhadnofamilyandfeltunmotivated.
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Quantitativeresults
2120patientsinthedrug-susceptibleTBprogramhadatreatmentoutcomein2013;66.0%had
pulmonarytuberculosis.Successfultreatmentwasachievedby77.5%ofpatients,while14.2%
defaulted.Theremainingpatientsdied(2.7%),transferredout(2.2%),failedtreatment(2.6%)
orhadachangeindiagnosis(0.8%).Table3showsthedemographicandclinicalcharacteristics
ofthepatients.
Patientswhohaddied,transferredout,orhadachangeindiagnosis(totaling122patients)
werenotincludedintheunivariateormultivariateanalysis.Theseanalyseswerethereforeper-
formedon1998patients.Ourunivariateanalysisshowedthatmalegender(OR:1.34,95%CI:
1.04–1.71),being35–59yearsofage(OR:1.54,95%CI:1.14–2.08),orbeing60yearsofageor
older(OR:1.84,95%CI:1.17–2.88)weresignificantlyassociatedwithdefault(Table4).
Table3. Demographicandclinicalcharacteristicsofstudypopulation.
Variables Total(n=2120)n(%)
Gender
Female 1221(57.6)
Male 899(42.4)
TypeofPatient
New 1677(79.1)
PreviouslyTreated 443(20.9)
Age
0–17 547(25.8)
18–34 945(44.6)
35–59 473(22.3)
60onwards 155(7.3)
SiteofTB
Pulmonary 1399(66.0)
Extrapulmonary 721(34.0)
PatientCategory
CAT-1 1802(85.0)
CAT-2 318(15.0)
TreatmentOutcome
TreatmentCompletion/Cure 1643(77.5)
Default 301(14.2)
TreatmentFailure 54(2.6)
DiagnosisChange 17(0.8)
Transferout 47(2.2)
Died 58(2.7)
StageofTreatmentDuringDefault
Intensive 189(62.8)
Continuous 112(37.2)
SmearStatusatBaseline*
Positive 575(60.4)
Negative 376(39.6)
*Smearstatusavailablefor951patientswithpulmonaryTB
TB=tuberculosis;CAT=treatmentclass;CAT-1=firsttreatmentwithfirst-linedrugs;CAT-2=retreatment
withfirst-linedrugs;Intensivephase=first2monthsoftreatment;Continuationphase=4–6monthsof
treatmentfollowingthefirst2monthsoftreatment
doi:10.1371/journal.pone.0142384.t003
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DefaultfromTuberculosisTreatmentinKarachi,Pakistan
Table4. Univariateanalysisofsociodemographicandclinicalvariablesassociatedwithdefault.*
Factor Non-default(n=1697)n(%) Default(n=301)n(%) OR(95%CI) p-value
Gender
Female 1002(86.5) 156(13.5) 1
Male 695(82.7) 145(17.3) 1.34(1.04–1.71) .020
TypeofPatient
New 1348(85.1) 236(14.9) 1
PreviouslyTreated 349(84.3) 65(15.7) 1.06(0.79–1.43) .685
Age
18–34 778(86.4) 122(13.6) 1
0–17 459(87.9) 63(12.1) 0.87(0.63–1.21) .422
35–59 356(80.5) 86(19.5) 1.54(1.14–2.08) .005
60onwards 104(77.6) 30(22.4) 1.84(1.17–2.88) .008
PatientCategory
CAT-1 1453(85.4) 248(14.6) 1
CAT-2 244(82.2) 53(17.8) 1.27(0.92–1.76) .147
SiteofTB
Pulmonary 1107(84.2) 208(15.8) 1
Extrapulmonary 590(86.4) 93(13.6) 0.84(0.64–1.09) .192
*1998patients;excludespatientswhodied,transferredout,orhadachangeindiagnosis
TB=tuberculosis;CAT=treatmentclass;CAT-1=firsttreatmentwithfirst-linedrugs;CAT-2=retreatmentwithfirst-linedrugs
doi:10.1371/journal.pone.0142384.t004
Afteradjustingforgender,siteofdisease,andpatientcategoryinthemultivariateanalysis,
being35–59yearsofagewassignificantlyassociatedwithdefault(aOR:1.49,95%CI:1.10–
2.03),aswasbeing60yearsofageorolder(aOR:1.76,95%CI:1.12–2.77)(Table5).
Table5. Multivariateanalysisofsociodemographicandclinicalvariablesassociatedwithdefault.*
Factor OR(95%CI) p-value
Gender
Female 1
Male 1.24(0.97–1.60) .087
Age
18–34 1
0–17 0.92(0.66–1.27) .604
35–59 1.49(1.10–2.03) .009
60onwards 1.76(1.12–2.77) .014
PatientCategory
CAT-1 1
CAT-2 1.18(0.84–1.64) .336
SiteofTB
Pulmonary 1
Extrapulmonary 0.92(0.70–1.21) .554
*1998patients;excludespatientswhodied,transferredout,orhadachangeindiagnosis
TB=tuberculosis;CAT=treatmentclass;CAT-1=firsttreatmentwithfirst-linedrugs;CAT-2=retreatment
withfirst-linedrugs
doi:10.1371/journal.pone.0142384.t005
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