Risk Factors of Typhoid Infection in the Indonesian Archipelago

14 Pages·2016·0.81 MB·English

RESEARCHARTICLE
Risk Factors of Typhoid Infection in the
Indonesian Archipelago
SandraAlba1*,MirjamI.Bakker1,MochammadHatta2,PaulineF.D.Scheelbeek1,
RessyDwiyanti2,RomiUsman2,AndiR.Sultan2,MuhammadSabir2,
NatanielTandirogang3,MasyhudiAmir3,YadiYasir3,RobPastoor1,StellavanBeers1,
HenkL.Smits1
1 KITBiomedicalResearch,RoyalTropicalInstitute(KIT),Amsterdam,TheNetherlands,2 Departmentof
MedicalMicrobiology,MolecularBiologyandImmunologyLaboratory,FacultyofMedicine,Hasanuddin
University,Makassar,South-Sulawesi,Indonesia,3 DepartmentMicrobiology,FacultyofMedicine,
MulawarmanUniversity,Samarinda,East-Kalimantan,Indonesia
a11111
*[email protected]
Abstract
OPENACCESS
Background
Citation:AlbaS,BakkerMI,HattaM,Scheelbeek
Knowledgeofriskfactorsandtheirrelativeimportanceindifferentsettingsisessentialto
PFD,DwiyantiR,UsmanR,etal.(2016)RiskFactors
ofTyphoidInfectionintheIndonesianArchipelago. developeffectivehealtheducationmaterialforthepreventionoftyphoid.Inthisstudy,we
PLoSONE11(6):e0155286.doi:10.1371/journal. examinetheeffectofhouseholdlevelandindividualbehaviouralriskfactorsontheriskof
pone.0155286
typhoidinthreeIndonesianislands(Sulawesi,KalimantanandPapua)intheEasternIndo-
Editor:DipshikhaChakravortty,IndianInstituteof nesianarchipelagoencompassingrural,peri-urbanandurbanareas.
Science,INDIA
Received:October23,2015 Methods
Accepted:April1,2016 Weenrolled933patientsabove10yearsofageinahealthfacility-basedcase-controlstudy
betweenJune2010andJune2011.Individualssuspectedoftyphoidweretestedusingthe
Published:June9,2016
typhoidIgMlateralflowassayfortheserodiagnosisoftyphoidfeverfollowedbybloodcul-
Copyright:©2016Albaetal.Thisisanopenaccess
turetesting.Casesandcontrolsweredefinedpost-recruitment:caseswereindividualswith
articledistributedunderthetermsoftheCreative
CommonsAttributionLicense,whichpermits acultureorserologypositiveresult(n=449);controlswereindividualsnegativetoboth
unrestricteduse,distribution,andreproductioninany serologyandculture,withorwithoutadiagnosisotherthantyphoid(n=484).Logistic
medium,providedtheoriginalauthorandsourceare
regressionwasusedtoexaminetheeffectofhouseholdlevelandindividuallevelbeha-
credited.
viouralriskfactorsandwecalculatedthepopulationattributablefraction(PAF)ofremoving
DataAvailabilityStatement:Dataareavailable
eachrisksignificantindependentbehaviouralriskfactor.
throughZenodo(http://dx.doi.org/10.5281/zenodo.
53987).
Results
Funding:ThisstudywasfundedbytheUBS
OptimusFoundationwithagrantawardedon5 Washinghandsatcriticalmomentsofthedayandwashinghandswithsoapwerestrong
October2009(https://www.ubs.com/global/en/ independentprotectivefactorsfortyphoid(OR=0.3895%CI0.25to0.58foreachunit
wealth_management/optimusfoundation.html).The
increaseinhandwashingfrequencyscorewithvaluesbetween0=Neverand3=Always;
funderhadnoroleinstudydesign,datacollection
OR=3.1695%CI=2.09to4.79comparingwashinghandswithsoapsometimes/nevervs.
andanalysis,decisiontopublish,orpreparationof
themanuscript. often).Theseeffectswereindependentoflevelsofaccesstowaterandsanitation.Upto
twothirdsofcasescouldbepreventedbycompliancetothesepractices(handwashing
CompetingInterests:Theauthorshavedeclared
thatnocompetinginterestsexist. PAF=66.895%CI61.4to71.5;useofsoapPAF=61.995%CI56.7to66.5).Eatingfood
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RiskFactorsofTyphoidInfectionintheIndonesianArchipelago
outinfoodstallsorrestaurantwasanimportantriskfactor(OR=6.995%CI4.41to10.8for
everyunitincreaseinfrequencyscore).
Conclusions
Majorgainscouldpotentiallybeachievedinreducingtheincidenceoftyphoidbyensuring
adherencetoadequatehand-washingpracticesalone.Thisconfirmsthatthereisapivotal
rolefor‘software’relatedinterventionstoencouragebehaviorchangeandcreatedemand
forgoodsandservices,alongsidedevelopmentofwaterandsanitationinfrastructure.
Introduction
Typhoidfeverisanacuteandoftenlife-threateningfebrileillnessestransmittedviathefecal-
oralroutebythebacteriumSalmonellaentericaserotypeTyphi.Individualsareinfectedby
ingestionofcontaminatedwaterorfoodbutalsoaftercontactwithapatientorex-patient.
Patientsmaybecomelife-longcarriersandtheseindividualsecretingthepathogenwiththeir
stoolformasignificantfactorinthemaintenanceofthepathogeninapopulation.Thepatho-
gendoesnotinfectanimals,andtherefore,transmissionisonlyfromhumantohuman.
Thereisalackofreliabledataontheburdenoftyphoid,becauseofthelimitedavailability
ofbloodcultureservicesandthechallengesassociatedwithimplementinglargescalefeversur-
veillancetechniquestomeasurediseaseincidence[1].Thelatestestimatessuggestthatthedis-
easecaused13.5millionillnessesgloballyin2010[2].Worldwide,thehighestincidencerates
oftyphoidfeverhavebeenrecordedinAfricaandAsia[2–3].InIndonesia,astudyconducted
intheslumsofJakartaestimatedtheincidencerateoftyphoidat148.7per100000person-
yearsintheagegroup2–4yearsold,180.3intheagegroup5–15yearsoldand51.2inthose
over16yearsofage,withameanageofonsetof10.2years[4].Withouteffectivetreatment,
typhoidfeverhasacase-fatalityrateof10–30%,butthisnumberisreducedto1–4%inthose
receivingappropriatetherapy[1].
HistoricallytheWorldHealthOrganisationhasmaintainedthepositionthattyphoidcon-
trolshouldrevolvearoundthetreatmentofacutecasescombinedwithimprovementsinwater
andsanitation[1].Twovaccinesarelicensedforuse—theoralTy21avaccineandtheinjectable
Typhoidpolysaccharidevaccine[5]—inhigh-risksettings.Althoughpositiveexperiencesin
Asiaarepavingthewayforarenewedfocusonvaccinationprogrammes[6–7],reducedexpo-
suretothediseasebymeansofimprovedwaterandsanitationremainsthecornerstoneof
typhoidprevention.However,thereisagrowingrecognitionthataccesstowaterandsanitation
aloneisnotsufficient—untilhygieneisproperlypracticed,bothathomeandinthecommunity
asawhole,thedesiredimpactofimprovedwaterandsanitationservicesonhealthrelatedout-
comes(typhoidincluded)cannotberealized[8–9].
Knowledgeofriskfactorsandtherelativeimportanceofaccesstowaterandsanitation
(‘hardware’),versusindividualbehavior(‘software’)[10]isessentialtodevelopeffectivehealth
interventions.Avarietyofriskfactorsfortyphoidfeverhavebeenreportedindifferentstudies
inIndonesiaandthesecanbegenerallydividedinfactorsassociatedwithlowlevelsofeduca-
tion,contactwithatyphoidpatient,lackofaccesstocleanwaterandsanitation,inadequate
hand-washingpracticesandpoorhygiene,aswellasconsumptionofstreetfoodanddrinks
[11–14].However,nostudytodatehassystematicallyassessedtherelativeimportanceof
‘hardware’vs.‘software’andacrossavarietyofsettingsinIndonesia,encompassingbothurban
andruralareas.Furthermoreitisnotknownhowmanycasescouldpotentiallybeavertedby
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RiskFactorsofTyphoidInfectionintheIndonesianArchipelago
reducing‘highrisk’behaviorwithoutinterveningonaccesstohardware.Inthisstudy,we
examinetheeffectofhouseholdlevelandindividualbehaviouralriskfactorsontheriskof
typhoidandestimatethepopulationattributablefactorassociatedwiththeremovalofmain
riskfactorsinthreeIndonesianislandsencompassingrural,peri-urbanandurbanareas.
MaterialsandMethods
Studydesignandpatientrecruitment
Atotalof933patientswererecruitedinacase-controlstudybetweenJune2010andJune
2011from14selectedhospitalsandhealthcentresinthreeIndonesianislands:inandaround
MakassarinSouthSulawesi(Sulawesi);Jayapura(Papua);SamarindainEast-Kalimantan
(Kalimantan)(Fig1).Healthfacilitieswerelocatedinarangeofrural,urbanandperi-urban
settings—whereperi-urbanareasaredefinedasareasatthemarginsofanurbanarea,intran-
sitionfromruraltourban.Healthcentreswereincludedbasedonhealthstaffavailability,
willingnesstoparticipate,aswellasaccessibilitytoalocaldiagnosticfacility(toenableeasy
transportofbloodculturematerial).ThisincludedtwofacilitiesinKalimantan(oneina
peri-urbanarea,oneinanurbanarea),threeinPapua(twoinperi-urbanareasandoneinan
urbanarea)andnineinSulawesi(twoinruralarea,threeinperi-urbanareasandfourin
urbanareas).
Thecriteriaforenrolmentinthestudywerethefulfillmentofatleast2ofthefollowing3
typhoidsuspicioncriteria:1)feveronthedayofconsultation(bodytemperaturemeasured
axillary>37.5°C);2)feverduration(cid:1)3days;3)headachesincethestartofthefever.Onlyindi-
vidualsabovetheageof10yearsonthedayofrecruitmentwereincludedinthestudy.
IndividualssuspectedoftyphoidweretestedbymeansofthetyphoidIgMlateralflowassay
fortheserodiagnosisoftyphoidfeverfollowedbybloodculturetesting(seeparagraphbelow
fordetails).Threegroupsofapproximatelyequalsizewererecruited:1)patientswhowerepos-
itivetoserologywereenrolledaspotentialcasesandafollow-upculturetestwasdone;2)
patientswhowerenegativetoserologybutforwhomaclinicalsuspicionoftyphoidremained,
wereenrolledaspotentialcontrolsandwerealsotestedbyculture;3)patientswhowerenega-
tivetoserologyandforwhomtherewasnoclinicalsuspicionoftyphoidandwerediagnosed
withanotherdiseasewererecruitedaspotentialcontrolsandnoculturetestingwasdone(Fig
2).Thisalgorithmbuildsuponthecomplementaritybetweenthelateralflowwhich,beingan
antibodytest,hasahighersensitivityforlaterstagepatients(from7daysonward)andblood
culturetestingwhichhasahighsensitivityforearlystagepatients.[15].Thisalgorithmwas
choseninconsultationwithallstaffinvolvedinthestudyinordertoaccommodate1)study
goals(introductionofserologicaltestinginremotehealthfacilitieswhereculturetestingisnot
routinelyconducted);2)primarydiagnosticconcerns(apositiveserologyinafebrilepatient
withanotherdiagnosisastyphoidmaybeduetosensitizationinthepastwhichwarrantsafol-
low-upofallserologicaltestwithculturetesting);and3)routineclinicalpractice,whichpriori-
tizedtheuseofculturetestingfornegativeserologyonlywhennootherdiagnosiscouldbe
found—despitethefactthatduringthefirstweekofthediseaseantibodiesareoftennotdetect-
able,whichwouldjustifyaculturetestforallnegativeserologicaltests.
TheproceduresforthetyphoidIgMlateralflowassaywhichdetectsspecificIgMantibodies
havebeendocumentedelsewhere[15].Testresultswereratedfrom1+to4+dependingonthe
stainingintensityatthetestlineandaresultwasconsideredpositivewhengreaterorequalto
1+.Bloodcultureswereperformedbytheinoculationof8mlfreshlycollectedvenopuncture
blooddirectlyintoaBactecplusaerobic/Fbottle.Bacterialcultureswereallowedtogrowfor24
hoursbyincubationat37°Cafterwhich1mlofbrothwasspreadona9cmdiameter,15mlSS
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RiskFactorsofTyphoidInfectionintheIndonesianArchipelago
Fig1.Locationofstudysitesandparticipatinghealthfacilities.
doi:10.1371/journal.pone.0155286.g001
Fig2.Diagnosticalgorithm.1Feveronthedayofconsultation(bodytemperaturemeasuredaxillary
>37.5°C);feverduration(cid:1)3days;headachesincethestartofthefever.2IgMlateralflowassay
doi:10.1371/journal.pone.0155286.g002
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RiskFactorsofTyphoidInfectionintheIndonesianArchipelago
agarplate.Afteranotherincubationfor72hoursat37°Cplateswereexaminedforcolonies
andindividualcolonieswerepickedandsubjecttobiochemicalidentification.
Individualbehaviouralriskfactorswerecollectedatrecruitmentandincludedcurrentand
pastillness,sanitaryconditionsandpractices,personalhygieneincludingfrequencyofhand
washing,(outdoor)eatinghabitsandtheuseandpreparationofsafedrinkingwater,recent
traveling,recentcontactwithatyphoidpatientsandknowledgeoftyphoidandtheprevention
oftyphoid.InadditionfromDecember2010onwardsaquestionnairewassubmittedtoa
householdcontactofeachtyphoidsuspecttoelicitinformationregardinghouseholdlevel
accesstowater,hygieneandsanitation.Householdleveldatawascollectedforasubsetof494
outof933individualsenrolledinthestudy.
Datacollectionwasconductedbytrainedstaffusingsemi-structuredandpre-testedques-
tionnaires.Informationwascollectedonpaperquestionnairesandsubsequentlyenteredinan
electronicdatabase.
Statisticalanalyses
Forstatisticalanalysesthefollowingcasedefinitionwasdefinedpost-recruitment:TypeI
caseswereindividualswithaculturepositiveresultregardlessofserologicalresult(c+/s+;
c+/s-);TypeIIcaseswereindividualswhohadaculturenegativebutseropositiveresults
(c-/s+);TypeIcontrolswereindividualsnegativetobothserologyandculture(s-/c-);TypeII
controlswereindividualsnegativetoserologyandwithadiagnosisotherthantyphoid(s-/d-).
Inthispaperweconductedthemainanalysescomparingallcontrols(TypeIandII)versusall
cases(TypeIandII).Sub-setanalyseswereconductedcomparingonlyTypeIcasesandType
Icontrols.
Theeffectofindividualandhouseholdlevelriskfactorswereexaminedbyfittinglogistic
regressions.Sincemanyindividualriskfactorswerecorrelated,webuiltcompositeindicators
tosummarisetheinformationfromgroupsofcollinearvariablesintoauniquevariable.An
overallhandwashingfrequencyscore(handwashingincriticalmomentsoftheday)wascre-
atedasthearithmeticmeanofindividualvariables:handwashingafterusingthetoilet,hand
washingbeforeeating,handwashingbeforefoodpreparation,handwashingafterchangedia-
pers,handwashingwhencominghome,handwashingbeforeprayers.Eachhandwashingvar-
iablewascodedatdatacollectiononacategoricalscalerangingfrom0(never)to3(always).
Theoverallhandwashingfrequencyscorewasthereforeacontinuousscorevariableranging
from0(neverwashesatcriticaltimes)to3(washesatallcriticaltimes).Similarlytwofre-
quencyscoresforeatingmealsathomeoroutwerecreatedoutofindividualcategoricalvari-
ablesdenotingthefrequencywithwhichbreakfast,lunchanddinnerwereconsumedathome
orout(i.e.restaurantorfoodstall).Thisresultedinacontinuousscorebetween0(nevercon-
sumesmealsathome/out)to3(alwaysmealsathome/out).
Weexaminedthepopulationattributablefraction(PAF)ofremovingeachindividualbeha-
viouralriskfactor,byislandandbytypeofsetting(urban,peri-urbanandrural)toassessthe
proportionofcaseswhichcouldbepotentiallyavertedbyremovingeachfactor.ThePAFesti-
matesandconfidenceintervalswereestimatedusingtheuserdefinedpunafcccommandin
Stata,whichimplementsamaximumlikelihoodestimationoftheattributablefractionfrom
logisticmodels[16].
AllanalyseswereconductedwithStata/SE12.1forWindows.
Ethics
ThemedicalethicalcommitteeoftheHasanuddinUniversityapprovedthestudy.Written
informedconsentwasobtainedfromliterateparticipantsortheirguardiansiftheparticipants
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wereminors.Oralinformedconsentwasobtainedfromallindividualsenrolledinthestudyor
theirguardians.Forilliterateparticipantswhoonlyprovidedoralconsent,consentwasdocu-
mentedwiththesignatureofawitness.Theuseoforalconsentforilliterateparticipantswas
specificallyapprovedbytheethicscommittee.
Results
Ofthe933patientsinthestudythefollowinggroupswererecruited:1)295individualswere
positivetoserologyandenrolledaspotentialcases,151(51.2%)ofwhichweretestedpositive
byculture;2)328individualswerenegativetoserologybutwithaclinicalsuspicionof
typhoidandenrolledaspotentialcontrols,154(46.9%)ofwhichweretestedpositivebycul-
ture;3)310individualswerenegativetoserologyanddiagnosedwithanotherdiseaseand
recruitedaspotentialcontrols.Outofthese310patients,12(3.9%)werediagnosedwithden-
guehemorrhagicfever,37(11.9%)withhepatitis,48(15.5%)withleptospirosis,65(21%)
withmalaria(21.0%),66(21.2%)withupperrespiratorytractinfection(21.3%)and82
(26.5%)remainedwithanunknowndiagnosis.Accordingthecategoricalcasedefinition
definedpost-recruitmentforanalyses,outofthe933recruitedpatients,305(32.7%)were
classifiedasTypeIcases;144(15.4%)asTypeIIcases;174(18.6%)asTypeIcontrols;and
310(32.2%)asTypeIIcontrols.Therewasonlyonecleartrendinsocio-demographicchar-
acteristicsacrosscasedefinitions:casesweremorelikelytoreporta“foodrelated”profession
thancontrols(Table1).
Householdcharacteristics
ThedistributionofhouseholdcharacteristicsbycasedefinitionrevealedthatTypeIcontrols
differedfromTypeIIcontrolsandappeartobegenerallymoresimilartocasesthancontrols
(S1Table)–theyhadworseaccesstowaterandsanitation,scoredworseintermsofhygiene
indicators(kitchencleanliness,ownershipofbinsetc)andwerefrompoorerhouseholds.
Thestrongestpredictoroftyphoidriskathouseholdlevelwasavailabilityofsoapnearthe
toilet,increasingtheoddsoverfour-fold(S2Table).Thiswascloselyfollowedbyassocia-
tionswithvariablesrelatedtosanitation,whichincreasedtheoddsoftyphoidbetweenupto
nearlythreefold(methodstoemptylatrines,numberofpeoplesharingalatrine).Various
variablesrelatedtowaterqualityandaccessibilitywereassociatedwiththeoddsoftyphoid,
increasingoddsbyfactorsofaround2(forexamplenumberofbucketsavailableinthe
householdfordrinking,cookingandcleaning,availabilityofwaternearthelatrine,water
treatment,watercolour,distancetonearestwaterpoint)aswellasfoodpreparation(number
ofhomecookedmealsperday,consumptionofrawvegetables,numberoftimesthekitchen
iscleanedperweek).Socio-economicvariableswerealsoassociatedwithhigheroddsof
typhoidinpoorerhouseholdslivinginnon-permanentortraditionalhouseswithoutfridge
orwastebins.
Householdcompositionwasnotsignificantly(p>0.10)associatedwiththeoddsoftyphoid
(numberofhouseholdmembers,numberofhouseholdmembersundertheageof12).
Althoughwateravailability(numberofbucketsavailable)andaccessibility(distancetonearest
watersource,availabilityofwaternearthelatrine)werepredictorsoftyphoidrisk,thetypeof
watersource(in-housetap,taponcompound,welloncompound,wellinvillage,rive/canal/
pond)andstoragecontainers(ember,drum,watertank),howwateristakenfromtheplaceit
isstored(scoopvs.tap)orwhetherwatertastedofiron(correlatedwithwatertaste—yellow
watermorelikelytotastelikeiron,waterwithnocolourmorelikelytohavenotaste)werenot
showntohaveaneffect.Similarly,therewasnoeffectofwherefoodforhouseholdconsump-
tionissourced(market,supermarket,stalls,peddlers).Althoughwastebinownershipwas
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Table1. Baselinecharacteristicsbycasedefinition.
Typhoidcasedefinition1
TypeICases TypeIICases TypeIControls TypeIIControls Total
N=305 N=144 N=174 N=310 N=933
Setting
Urban 176 57.7% 78 54.2% 92 52.9% 169 54.5% 515 55.2%
Peri-urban 93 30.5% 55 38.2% 54 31.0% 99 31.9% 301 32.3%
Rural 36 11.8% 11 7.6% 28 16.1% 42 13.5% 117 12.5%
Island
Kalimantan 77 25.2% 26 18.1% 53 30.5% 78 25.2% 234 25.1%
Papua 59 19.3% 34 23.6% 31 17.8% 63 20.3% 187 20.0%
Sulawesi 169 55.4% 84 58.3% 90 51.7% 169 54.5% 512 54.9%
Seks
Male 144 47.2% 70 48.6% 82 47.1% 154 49.7% 450 48.2%
Female 161 52.8% 74 51.4% 92 52.9% 156 50.3% 483 51.8%
Religion
Christian 44 14.4% 21 14.6% 26 14.9% 43 13.9% 134 14.4%
Hindu 6 2.0% 2 1.4% 2 1.1% 5 1.6% 15 1.6%
Muslim 255 83.6% 121 84.0% 146 83.9% 262 84.5% 784 84.0%
Agecategory(inyears)
>=10–20 82 26.9% 27 18.8% 39 22.4% 71 22.9% 219 23.5%
>=20–30 94 30.8% 45 31.3% 55 31.6% 92 29.7% 286 30.7%
>=30–40 72 23.6% 35 24.3% 36 20.7% 61 19.7% 204 21.9%
>=40–50 32 10.5% 22 15.3% 26 14.9% 44 14.2% 124 13.3%
>=50 25 8.2% 15 10.4% 18 10.3% 42 13.5% 100 10.7%
Profession
Low-skilledlabour 46 15.1% 23 16.0% 32 18.4% 34 11.0% 135 14.5%
High-skilledlabour 7 2.3% 17 11.8% 12 6.9% 15 4.8% 51 5.5%
Homebasedorunemployed 127 41.6% 67 46.5% 85 48.9% 144 46.5% 423 45.3%
Student 80 26.2% 29 20.1% 37 21.3% 84 27.1% 230 24.7%
Foodrelated 14 4.6% 2 1.4% 1 0.6% 2 0.6% 19 2.0%
Farmer 31 10.2% 6 4.2% 7 4.0% 31 10.0% 75 8.0%
Education
None 82 26.9% 28 19.4% 35 20.1% 72 23.2% 217 23.3%
Elementary 94 30.8% 51 35.4% 69 39.7% 94 30.3% 308 33.0%
Juniorhigh 71 23.3% 45 31.3% 45 25.9% 77 24.8% 238 25.5%
Higherthanjuniorhigh 58 19.0% 20 13.9% 25 14.4% 67 21.6% 170 18.2%
1TypeIcontrolswereindividualsnegativetobothserologyandculture(s-/c-);TypeIIcontrolswereindividualsnegativetoserologyandwithadiagnosis
otherthantyphoid(s-/d-);TypeIcaseswereindividualswithaculturepositiveresultregardlessofserologicalresult(c+/s+;c+/s-);TypeIIcaseswere
individualswhohadaculturenegativebutseropositiveresults(c-/s+);
doi:10.1371/journal.pone.0155286.t001
foundtobeaprotectivefactor,whetherthewastebinwascovered,whatkindofwastedisposal
wasinplace(burning,wasteremovalservice,disposedingutter/river,holeintheground)did
nothaveanyeffect.Therewasnoeffectwithregardstoreportedfloodinthelast12months
noruseoffaecesasfertilizers(notreportedbyanyparticipant).
Duetohighcollinearityinthevariablesfromthehouseholdprofileitwasnotpossibleto
buildamultivariatemodeltoelicitindependentriskfactorsoftyphoidathouseholdlevel.
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Individualbehaviour
Graphicalanalysesandresultsfromthelogisticregression(bothunivariateandmultivariate)
revealedassociationswithonlythreebehaviouralvariables:handwashingandwashingwith
soapwerestronglyprotective,whereaseatingmealsoutwasastrongriskfactorasshowninFig
3andTable2.Similarlytothehouseholdprofileanalysesreportedabove,analysesatindividual
levelrevealedthatTypeIcontrolsdifferintermsofbehaviourfromTypeIIcontrols,andare
moresimilartothecases—TypeIcontrolshavelowerhandwashingfrequencyandnever
reportusingsoap.
Inthemultivariatemodel,foreveryunitincreaseinthehandwashingscoretherewasan
estimated62%reductionintheoddsofinfection;peoplewhoreportedtowashtheirhands
withsoapsometimesorneverhadthreefoldhigheroddsthanthosewhowashedtheirhands
often,whereastherewasnosignificantdifferencecomparedtothosewhoreportedtoalways
washtheirhands;eatingmealsoutincreasedtheoddsofinfectionbyafactorof6.9.These
effectsfromthefinalmultivariatemodeldidnotchangebymorethan10%whenadding
thefollowingsignificanthandwashingrelatedhouseholdlevelfactorstothemodel(onthe
subsetofindividualsforwhombothindividuallevelandhouseholdleveldatawasavailable):
numberofbucketsofwateravailable(n=478),availabilityofsoapnearthelatrine(n=487),
availabilityofawatersourcenearthelatrine(n=487),anddistancefromthenearestwater
source(n=492)(resultsnotshown).
Fig3.Distributionofindividuallevelriskfactorsbycasedefinition[1].1TypeIcontrolswereindividuals
negativetobothserologyandculture(n=305);TypeIIcontrolswereindividualsnegativetoserologyand
withadiagnosisotherthantyphoid(n=144);TypeIcaseswereindividualswithaculturepositiveresult
regardlessofserologicalresult(n=174);TypeIIcaseswereindividualswhohadaculturenegativebut
seropositiveresults(n=310);2Continuousscorewithvaluesbetween0=Neverand3=Always.3
Categoricalvariable0=Sometimes/Never,1=Often,2=Always.4Categoricalvariable1=Lessthanoncea
week,2=Onceaweek,3=Fewtimesaweek,4=Everyday
doi:10.1371/journal.pone.0155286.g003
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RiskFactorsofTyphoidInfectionintheIndonesianArchipelago
Table2. Estimatedeffectofindividuallevelbehaviouralriskfactorsontheoddsoftyphoid1,2.
Univariate Multivariate(N=933)
N OR 95%CI Sig.3 OR 95%CI Sig.3
Handwashingfrequencyscore4 933 0.26 0.20to0.35 <0.001 0.38 0.25to0.58 <0.001
Useofsoap 933 <0.001 <0.001
Often 1 1
Sometimes/Never 3.84 2.73to5.40 <0.001 3.16 2.09to4.79 <0.001
Always 0.61 0.37to0.99 0.049 0.60 0.33to1.07 0.083
Eatingmealsathomefrequencyscore4 933 0.92 0.71to1.19 0.520
Eatingmealsoutfrequencyscore4 933 2.30 1.63to3.24 <0.001 6.90 4.41to10.80 <0.001
Rawvegetableconsumptionathome 933 0.169
Fewtimesaweek 1
Everyday 1.12 0.84to1.51 0.431
Once/lessaweek 0.80 0.57to1.12 0.192
Latrineusage 906 0.417
Often 1
Sometimes/Never 1.15 0.81to1.65 0.430
Always 1.21 0.89to1.64 0.215
Placesusedtodefecate 933 0.925
Onlylatrines 1
Field 0.98 0.72to1.34 0.919
Pond/river/canal 0.77 0.56to1.06 0.108
1LogisticregressioncomparingcasesTypeIandTypeII(n=449)tocontrolsTypeIandII(n=484)
2Theeffectofcontactwithatyphoidpatientcouldnotbeestimatedasthemajorityofpatients(73%)didnotknowtheanswertothequestion.
3P-valuesreported:Waldtestofsignificanceofeffect,LLRtestofsignificanceofvariableinthemodel.
4Continuousscorewithvaluesbetween0=Neverand3=Always
doi:10.1371/journal.pone.0155286.t002
Thesub-setanalysescomparingTypeIcasestoTypeIcontrolsdidnotentirelyconfirmthe
mainanalyses.Thisismainlybecause,ascanbeseeninS1TableandFig3,anddiscussed
above,TypeIcontrolsaremoresimilartoTypeIandTypeIIcasesthantoTypeIIcontrolsin
householdcharacteristicsandbehavior.Asaconsequenceeffectswereeitherlessstrongand/or
nolongersignificantinthesub-setanalyses(S3Table),whichmeansthattheeffectspresented
inthemainanalysesarelikelytounderestimatethetrueeffects:TypeIcontrols,whichare
actuallymoresimilartocases,areaggregatedtogetherwithothermoregenuineTypeIIcon-
trolsthusdilutingeffects.
WecalculatedthePAFfortheremovalofeachriskfactorbytypeofsetting(Table3)andby
island(Table4)basedontheunivariatemodels(Table2).Acrossallsettingsapproximately
twothirdsofcasescouldpotentiallybeavertedifpeoplewashedtheirhandswithsoapoftenor
alwaysversussometimesornever.Similarlyapproximatelytwothirdsofcasescouldbeaverted
withmorefrequenthandwashing,i.e.ifeveryonewashedtheirhandsinallcriticalmomentsof
thedayoftenoralwaysvs.sometimesornever.Oneinfivecasescouldbeavertedbynoteating
mealsout.ThePAFassociatedwithuseofsoapwasespeciallyhighinruralareaswhere92%
ofcasescouldbeavertedwithuseofsoap,becausetheORassociatedwithsoapuseismuch
higherinthissubgroupthaninothers(OR=26.72,95%CI=6.00to118.83),whereastheprev-
alenceofsoapuseissimilaracrosssettings(overall39%ofallindividualsrespondedwashing
theirhandswithsoapinallcriticalmomentsoftheday).ThePAFassociatedwitheatingmeals
outwasthehighestinKalimantanandinperi-urbanwhereestimatedeffectswerehigherthan
PLOSONE|DOI:10.1371/journal.pone.0155286 June9,2016 9/14
RiskFactorsofTyphoidInfectionintheIndonesianArchipelago
Table3. Populationattributablefraction(PAF)and95%CIofincreasedoddsoftyphoidinfectionforeachbehaviouralriskfactor,bytypeof
setting1.
Setting
Urban Peri-urban Rural Total
N=515 N=301 N=117 N=933
Useofsoap2 63.2 49.6 92.2 61.9
(56.7to68.8) (36.5to60.0) (84.5to96.0) (56.7to66.5)
Handwashing3 65.0 74.1 53.8 66.8
(57.5to71.1) (66.1to80.3) (23.1to72.2) (61.4to71.5)
Eatingmealsout4 15.8 33.8 -6.8 19.3
(4.9to25.4) (22.3to43.7) (-4.0to18.7)5 (11.7to26.3)
1OddsratiosobtainedfromunivariatelogisticregressioncomparingcasesTypeIandTypeII(n=449)tocontrolsTypeIandII(n=484)
2Exposure:washinghandswithsoapoftenoralwaysvs.sometimesornever
3Exposure:washinghandsincriticalmomentsofthedayaveragescore>=2(oftenoralwaysvs.sometimesornever)
4Exposure:nevereatingoutvs.eatingoutsometimes,oftenoralways.
5PAFisnegativebecauseinthissubgroupeatingmealsoutisaprotectivefactor(OR=0.81,95%CI=0.36to1.80).ThePopulationProtectiveFactor
(PPF)is13.1%(95%CI-46.6%to48.5%)
doi:10.1371/journal.pone.0155286.t003
inothergroups(Kalimantan:OR=7.7295%CI=4.23to14.10;peri-urbanareas:OR=2.48
95%CI=1.55to3.94)andwherethepracticeismoreprevalent(53.8%ofindividualsinKali-
mantanand45%ofindividualsinperi-urbanareasreportedeatingmealsoutsometimes,often
oralwayscomparedto40%overall).ThePAFassociatedwitheatingmealsoutinruralareas
andinSulawesi(wherealltheruralfacilitieswerelocated)wasclosetozeroandnotsignificant.
Knowledgeaboutpreventionandtransmission
Thedataregardingknowledgeoftyphoidtransmissionanditspreventionwasmissingfor613
(65.6%)individualswhodidnotanswerthecorrespondingquestionsforunclearreasons(no
substantialdifferencesacrosstypeofsetting,island,sex,age,religion,althoughtherewere
Table4. Populationattributablefraction(PAF)and95%CIofincreasedoddsoftyphoidinfectionforeachbehaviouralriskfactor,byisland1.
Island
Kalimantan Papua Sulawesi Total
N=234 N=187 N=512 N=933
Useofsoap2 61.5 53.7 66.9 61.9
(48.2to71.3) (45.7to60.7) (59.6to72.9) (56.7to66.5)
Handwashing3 73.8 89.2 51.9 66.8
(65.2to80.4) (84.3to92.5) (40.4to61.2) (61.4to71.5)
Eatingmealsout4 69.3 37.6 -4.5 19.3
(62.4to74.9) (15.9to53.7) (-1.7to6.6)5 (11.7to26.3)
1OddsratiosobtainedfromunivariatelogisticregressioncomparingcasesTypeIandTypeII(n=449)tocontrolsTypeIandII(n=484)
2Exposure:washinghandswithsoapoftenoralwaysvs.sometimesornever
3Exposure:washinghandsincriticalmomentsofthedayaveragescore>=2(oftenoralwaysvs.sometimesornever)
4Exposure:nevereatingoutvs.eatingoutsometimes,oftenoralways.
5PAFisnegativebecauseinthissubgroupeatingmealsoutisaprotectivefactor(OR=0.8495%CI=0.57to1.25).ThePopulationProtectiveFactor
(PPF)is11.3%(95%CI-17.0%to32.7%)
doi:10.1371/journal.pone.0155286.t004
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