Accessing MDR-TB exposed Households: the PHOENiX MDR-TB ... · Accessing MDR-TB exposed Households:...
Transcript of Accessing MDR-TB exposed Households: the PHOENiX MDR-TB ... · Accessing MDR-TB exposed Households:...
AccessingMDR-TBexposedHouseholds:thePHOENiXMDR-TB
FeasibilityStudy
GavinChurchyard
(MBBCh,FCP(SA),FRCP(Edin),MMED,PhD)Co-ChairofPHOENIxFeasibilityStudyandMainTrial
MDRTBinHouseholdContacts� ContactsofMDRTBpa0entshaveahighriskofTBinfec0onanddisease
� VastmajorityofMDRTBinchildrenarisesfromhouseholdtransmission
• Systema0creviewofobserva0onalstudiesofcontactsofdrug-resistantindexcases• 4–8%propor0onwithincidentTB• 44–72%ofincidentTBaredrug-resistant
Shahetal.ClinInfectDis2014CainKPetal.IntJTubercLungDis2010
� Treatmentofpresump0veMDRTBinfec0onnotrecommended� Qualityofevidenceisseriouslylimited
� Recommendstrictclinicalobserva0onandclosemonitoringforTBdiseaseforatleasttwoyears
� ThereremainsanurgentneedfortrialsofTBpreven0vetherapyforHHcontactsofMDRTBpa0ents,par0cularlyforthoseathighriskincludingHIV-infected,TST+andyoungchildrentoinforminterna0onalevidence-basedrecommenda0ons
WHO2014GuidelinesforPrevenNveTherapyforMDRTBContacts
Recommenda)onsandResearchGaps
ProtecNngHouseholdsOnExposuretoNewlyDiagnosedIndexMulNdrug-ResistantTuberculosisPaNents
(A5300B/I2003B/PHOENIx)StudyHypothesis� Trea0ngHIV-infectedandotherchild,adolescentandadulthouseholdcontactsofMDRTBpa0ents,includingpre-XDRTBandXDRTB,whoareathighriskofdevelopingTBwithdelamanidwillsubstanNallyreducetheriskofdevelopingTB,comparedtoisoniazid
PHOENIxFeasibilitystudy
ObjecNves� Todescribethefeasibilityofiden0fying,recrui0ng,andcharacterizingadultMDRTBindexcasesandtheiradultandchildhouseholdcontacts
� TodescribetheprevalenceofLTBI,TBdiseaseandHIVinfec0onamongadultandchildhouseholdcontacts
Design� Cross-sec0onalstudywith1yearfollow-up
Samplesize� 300adultMDRindexcasesandalleligiblehouseholdcontacts
PopulaNon� IndexCase:Anadult(18yearsorolder)withpulmonaryMDRTB� Householdcontact:Apersonwholivesinthesamedwellingunitandsharesthesamehousekeepingarrangementsastheindexcase,andwhoreportsexposurewithin6monthspriortotheindexcasestar0ngMDRTBtreatment
Methods
Site-level� MDRTBcaseload� Resourceu0liza0onsurvey
IndexCases� Medicalhistory� Documenta0onofchestimagingandHIVstatus
� Sputumfordrug-suscep0bilitytes0ng
EvaluaNons
HouseholdContacts� Householdenumera0on� Medicalhistory� Documenta0onofHIVstatus(HIVtes0ng,ifunknown)
� LatentTBinfec0ontes0ng� Chestx-ray� RespiratorysamplesforTBdiagnosis� Knowledge,a_tudeandprac0ces(KAP)survey
PHOENIxFeasibilityStudySites
Botswana(1)Brazil(1)Hai0(1)Kenya(1)India(2)Peru(2)SouthAfrica(8)Tanzania(1)Thailand(2)Zimbabwe(1)
16sitesacNvated4sitesnotacNvated
MDRTBIndexCaseEnrollmentIndexCasesApproached
(Oct2015–Mar2014)410
IndexCasesScreened396(97%)
IndexCasesEnrolled308(78%)
3(3%)doesnothaveMDRTB2(2%)hasnotstartedMDRTBtreatment1(1%)illnessthatwouldinterfere1(1%)nohouseholdmember1(1%)duplicatescreeningnumber69(78%)Otherreason11(13%)unknown
Reasonsfornon-enrollment(n=88)
HouseholdContactsEnrollment
HHCreasonsfornotenrolling(n=308)HouseholdContacts
Enumerated*(*basedonn=305household)
1317
HouseholdContactsEnrolled**
(**basedonn=308households)
1018(77%)
28(9%)unabletocontact39(13%)notwilling,noreasongiven57(19%)donotwanttopar0cipateinresearch65(21%)toobusy1(<1%)fearofs0gma20(6%)ineligible63(20%)otherreasons35(11%)missingdata
ParNcipantCharacterisNcsCharacterisNc
Index(N=308)
HHC(N=1018)
Medianage,years(range) 36(18-74) 26Female 133(43%) 600(59%)*Countries(#sites)Botswana(1)Brazil(1)HaiN(1)India(2)Kenya(1)Peru(2)SouthAfrica(7)Thailand(1)
10(3%)10(3%)16(5%)58(19%)8(3%)63(20%)133(43%)10(3%)
38(4%)17(2%)52(5%)206(20%)12(1%)203(20%)460(45%)30(3%)
*14pregnantwomen
Indexcasesn=308
� Iden0fiedat� Communityclinics 53%� Generalhospital 16%� CRS 13%� ReferraltoCRS 11%� Other 1%
� Documenta0onofDSTfromlocallab� All308rifampinresistance� Only232(75%)hadINHresistancedocumented
MDRTBIndexCaseCharacterisNcs
CharacterisNc
Index(N=308)
HIV-infected 112(36%)
Diabetes 25(8%)
Currentorformersmoking 133(43%)
PreviousTB 147(48%)Chestx-raycavitaNon 201(65%)AFBsmearposiNve(n=211) 148(70%)
MDRTBtreatmentduraNon(median) 6.2weeks
AgeDistribuNonofHouseholdContacts
1%9%
25%
48%
17%
0%
10%
20%
30%
40%
50%
60%
0
100
200
300
400
500
600
<1 1-<5 5-<18 18-<50 >=50
Pediatriccapacityvariable:2-50%enrolmentofchildren<5yrsacrosssites
HIVTesNng� Overall
� 78%ofHHChadunknownHIVstatuspriortostudyentry� 71%ofHHCagreedtoHIVtes0ng� 26(5%)newinfec0onsiden0fied
� VariableuptakeofHIVtes0ngacrosssites� 9siteswith>80%uptakevs.4siteswith<50%uptake� Loweruptakeinage2-17yo(52-65%)vs.<2yrs(77%)andadults(78%)
� ReasonsfornotofferingorrefusingHIVtes0ng:� Parent/guardiannotavailabletoconsentorParent/guardianrefusal� NoIRBapprovalforHIVtes0nginchildren
� ParentsofchildHIVnega0ve(riskpercep0on)
LatentTBInfecNonLTBITesNng n(%)
NoTSTdone* 300(30%)
TSTtested 705(64%)
TST+ 392(56%)
TST- 304(43%)
Testedbutnoresult 9(1%)
NoIGRAdone 26(3%)
IGRAtested 973(97%)
IGRA+ 629(65%)
IGRA- 330(34%)
Testedbutnoresult 14(1%)
LTBI N(%)
TST+orIGRA+ 708(70%)
TST-andIGRA- 272(27%)
Unknown 27(3%)
LTBIstatuswithcombinedtesNng
*TSTnotdoneat3of16sites(2Peruand1SouthAfrica)
LatentTBInfecNonLTBITesNng n(%)
NoTSTdone* 300(30%)
TSTtested 705(64%)
TST+ 392(56%)
TST- 304(43%)
Testedbutnoresult 9(1%)
NoIGRAdone 26(3%)
IGRAtested 973(97%)
IGRA+ 629(65%)
IGRA- 330(34%)
Testedbutnoresult 14(1%)
LTBI N(%)
TST+orIGRA+ 708(70%)
TST-andIGRA- 272(27%)
Unknown 27(3%)
LTBIstatuswithcombinedtesNng
*TSTnotdoneat3of16sites(2Peruand1SouthAfrica)
LatentTBInfecNonLTBITesNng n(%)
NoTSTdone* 300(30%)
TSTtested 705(64%)
TST+ 392(56%)
TST- 304(43%)
Testedbutnoresult 9(1%)
NoIGRAdone 26(3%)
IGRAtested 973(97%)
IGRA+ 629(65%)
IGRA- 330(34%)
Testedbutnoresult 14(1%)
LTBI N(%)
TST+orIGRA+ 708(70%)
TST-andIGRA- 272(27%)
Unknown 27(3%)
LTBIstatuswithcombinedtesNng
*TSTnotdoneat3of16sites(2Peruand1SouthAfrica)
TST+andIGRA+byCountry� TST+ � IGRA+
8%
78%
35%
60%
50%
0
65%
13%
56%
0% 20% 40% 60% 80% 100%
Botswana
Brazil
HaiN
India
Kenya
Peru
SouthAfrica
Thailand
Overall
Notdone
55%
76%
73%
74%
70%
56%
80%
47%
72%
0% 20% 40% 60% 80% 100%
Botswana
Brazil
HaiN
India
Kenya
Peru
SouthAfrica
Thailand
Overall
YieldofContactTracingn=1016contacts
� Signs/symptomsrelatedtoTB� 23%HHCs<15yearsand24%of>=15years
� CXR� 971(96%)gotCXR� 169(17%)abnormal
� 130(13%)prevalentTBcases� Possible71,7%� Probable33,3%� Confirmed26,3%
� Yieldvariedbysite
PotenNallyEligibleHighRiskHouseholdContacts
CharacterisNc N(%)
Ineligible(hadprevalentTBornothighrisk) 350(34%)
PotenNallyeligible<5years≥5yearsandHIV+≥5yearsandTSTorIGRA+
666(66%)66(10%)60(9%)540(81%)
Median#ofeligiblecontactsperhousehold 2(IQR1–3)
WillingnesstotakePrevenNvetherapy
• HHCwillingnesstotakepreven0vetherapywashigh(79%)withsignificantsite-levelvaria0on
n=741HHCsmedianage3362%women42%primaryorlesseduca0on
Suryavanshi,MurilletalPosteratAmericanThoracicSociety2017
ResourceuNlizaNon
� 16sitesmade512aoemptstoevaluate308households� upto5aoemptsperhousehold
� MedianHHsizewas4peopleplusindexcase� Range1–21persons
� Median0mespentbysitestaffperaoemptwas4hours
� Range1to24hours
InfecNoncontrolHousehold&faciliNes� N95respiratorswerewornbystudystaffin15/16sites� Indexcasesworesurgicalmasksinallsites� SputumcollectedinaseparateareainallclinicsTransportaNonofparNcipants� Par00onedvehicleavailableathalfthesites� N95respiratorswornbydriversat82%ofsites� Surgicalmaskswornbypar0cipantsatallsites� Windowsopenwhentranspor0ngpar0cipantsatallsites
Sitechallenges� TSTaccess� UptakeofHIVtes0ng� Recruitmentofchildren� Sufficientstaffing� Travel/logis0cs
� Safetyofoutreachteams� Needformul0plevisits,flexibilityinhours/loca0on
� Occupa0onalexposurerisk/infec0oncontrol� Challengesofwearingpersonalprotec0veequipment� Transpor0nghouseholdcontactstothesite� Needforseparatesputumsamplingareas
� S0gma
Conclusion� EnrollingMDRTBindexcasesandhouseholdcontactsisfeasible� StrategiestoimproveHIVtes0ngbyHHCisrequired� Contactinves0ga0onofchildrenrequiresstrengthening� Householdcontactinves0ga0onsprovideahighyieldbutarelaborintensiveandrequiremul0pleresources
� Highwillingnesstopar0cipateintrialofpreven0vetherapy
ProtocolTeam� Co-Chairs:GavinChurchyard,AmitaGupta,AnnekeHesseling,SusanSwindells� ClinicalRepresentaNves:DanielJohnson,RohanHazra,ElizabethSmith� ClinicalTrialsSpecialists:LindaG.Naini,LaraHosey� StaNsNcians:MichaelHughes,SoyeonKim� DataManager:LynneJones� DAIDSPharmacist:ThucumaSise� Pharmacologists:KellyDooley,KimberlyK.Scarsi� InvesNgators:RichardE.Chaisson,MarkHarrington,SharonNachman,SaritaShah� ConsultantCardiologist:RichardFriedman� ConsultantMicrobiologist:Anne-MarieDemers� FieldRepresentaNves:SavitaM.Kanade,JanetNicotera� LaboratoryTechnologists:PatriciaAnthony,ChristopherLane� CommunityScienNficSubcommipeeRepresentaNves:UjwalAmarKadam,RonaldSsenyonga� InternaNonalSiteSpecialist:AkbarShahkolahi� LaboratoryDataManager:AdamManzella� IndustryRepresentaNve:JeffreyHavin
SiteInvesNgatorsandStudyTeams� RodneyDawsonandKimNarunsky-UniversityofCapeTownLungInsNtuteSouthAfrica(Site31792)Fund110205� AlbertoMendozaandFannyRosas-BarrancoCRSPeru(Site11301)Grant5UM1AI069438-10
� JessicaRiosandLilianaVallejos-SanMiguelCRSPeru(Site11302)Grant110199� VidyaMaveSushantMeshram-ByramjeeJeejeebhoyGovernmentMedicalCollegeCRS(Site31441)GrantU01AI069497
� NKumarasamyandEasterThamburaj-ChennaiAnNviralResearchandTreatment(CART)CRS(Site11701)GrantUM01A1069432
� KylaCominsandVictoireTicha-TASKCRS(Site31718)GrantUM1AI069521� FrancescaConradieandRalinahMaepa-WitsHelenJosephHospitalCRS(Site11101)GrantAI069463
� MarkHatherillandJus0nShenje-SouthAfricanTuberculosisVaccineIniNaNve(SATVI)(Site31793)Grant5UM1AI068636-10
� SandyNereoeFontainandStalzCharlesVilbrun-GHESKIOCentersIMIS(Site31730)Grant5UM1AI069421� AnthonyGarcia-PratsandPetraDeKoker-DesmondTutuTBCentre-StellenboschUniversity(DTTC-SU)(Site31790)
� AidaAsmelashandAyotundeOmozoarhe-GaboroneCRS(Site12701)GrantUM1AI069456� SupalertNedsuwanandTimRCressey-PHPT-ChiangraiPrachanukrohHospital(Site5116)GrantHHSN275201300003C
� DebraPetersandBreoMansfield-SowetoACTGCRS(Site12301)Grant5UM1AI069453
� UmeshGLallooandRosieMngqibisa-DurbanInternaNonalCRS,EnhancingCareFoundaNon(Site11201)Grant2UM1AI069432-08� AnaCris0naGarciaFerreiraandMariaReginaRocha-InsNtutoNacionaldeInfectologia-INI/Fiocruz(Site12101)Grant5UM1AI069476-09
� ChristopherMugahandElishaOkeyo-Kisumu(KEMRI/CDC)CRS(Site31460)Grant5UM1A1068636-09