PreventionPrevention ofof perinatalperinatal HBVHBV transmission:transmission: EvaluationEvaluation ofof programsprograms andand successsuccess storiesstories fromfrom CentralCentral AsiaAsia andand KazakhstanKazakhstan Michael O. Favorov MD, Ph.D., D.Sc. Ludmila Mosina MD CDC Central Asia Office Division of Viral Hepatitis, NCID, Centers for Disease Control and Prevention Key Elements in Developing a Program to Prevent HBV Transmission Define epidemiology of disease Quantify disease burden Develop a comprehensive prevention strategy Identify resources to implement program Define epidemiology of disease and quantify disease burden ReportedReported AcuteAcute ViralViral HepatitisHepatitis IncidenceIncidence RateRate inin CentralCentral AsiaAsia byby Country,Country, 19871987--20052005 1600 Kazakhstan 1400 Kyrgyzstan p 1200 e Tajikistan r 1000 Turkmenistan 1 0 Uzbekistan 0 800 0 600 0 0 400 200 0 7 8 9 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 8 8 8 9 9 9 9 9 9 9 9 9 9 00 Year 2 EtiologyEtiology ofof acuteacute viralviral hepatitishepatitis inin KazakhstanKazakhstan,, 20042004 non A-C HВV - 0,9% 15,5% HDV - 0,1% HСV - 2,5% HЕV- 0,02% HАV - 81,0% AcuteAcute ViralViral HepatitisHepatitis SentinelSentinel SurveillanceSurveillance Sites,Sites, KyrgyzstanKyrgyzstan 20002000 Total Total CCaasesses repor reportedted – –20,42220,422 SentinelSentinel S Sitesites CaseCasess – –11,178,178 (5.8%) (5.8%) 20012001 Total Total casescases repor reportedted – –111,3981,398 SentinelSentinel S Sitesites CaseCasess – –679679 (5.9%) (5.9%) Jaundice EtiologyEtiology ofof AcuteAcute ViralViral HepatitisHepatitis inin KyrgyzstanKyrgyzstan,, SentinelSentinel SurveillanceSurveillance Data,Data, 20002000--20052005 HAV 4% HAV+HCV 2% 12% HAV+HBV HAV+HBsAg 2% HBV HBV+HCV 18% 54% HDV HCV 5% NANC 1% 2% N=3898 ChronicChronic liverliver diseasesdiseases reportedreported inin Turkmenistan,Turkmenistan, 19891989--19951995 2300 2200 2100 2000 1900 1800 per 100 000 1700 1600 1500 HDV super-infection 1400 1300 89 90 91 92 93 94 95 SerologicallySerologically defineddefined viralviral hepatitishepatitis B,B, C,C, andand andand DD amongamong patientspatients withwith chronicchronic liverliver diseasesdiseases AshgabatAshgabat,, Turkmenistan,Turkmenistan, 19951995 9.3% 1.3% HBV 44.0% 22.0% HBV+HCV HDV HDV+HCV HCV Other 2.0% 21.3% N=300 EstimatedEstimated ViralViral HepatitisHepatitis DiseaseDisease BurdenBurden inin CentralCentral AsiaAsia RegionRegion priorprior toto HBHB UniversalUniversal ImmunizationImmunization ImplementationImplementation Average number of patients per year : Acute Viral Hepatitis - 220 000 Chronic Liver Diseases 1 025 750 Average number of Deaths per year : Acute Viral Hepatitis - 2 310 Chronic Liver Diseases -12 265 SinceSince 19961996 CDCCDC CentralCentral AsiaAsia officeoffice hashas beenbeen workingworking inin closeclose collaborationcollaboration withwith MinistriesMinistries ofof HealthHealth inin thethe fivefive countriescountries ofof thethe regionregion TechnicalTechnical supportsupport fromfrom DivisionDivision ofof ViralViral Hepatitis,Hepatitis, NCIDNCID,, CDCCDC,, WHO,WHO, andand UNICEF;UNICEF; FinancialFinancial supportsupport fromfrom USAIDUSAID CACA Mission,Mission, andand GAVIGAVI;; DevelopedDeveloped andand implementedimplemented ComprehensiveComprehensive HepatitisHepatitis BB PreventionPrevention ProgramProgram inin thethe regionregion HepatitisHepatitis BB UniversalUniversal NewbornsNewborns ImmunizationImmunization StatusStatus inin CARCAR,, 19981998 Sustainable Programs Government funds Coverage > 85% <5% 0% 0% 0% HepatitisHepatitis BB UniversalUniversal NewbornsNewborns ImmunizationImmunization StatusStatus inin CARCAR,, 20012001-- 20062006 Since 2001 Sustainable Programs 1998 (Government funds) Coverage > 85% 2001 (GAVI funds) Coverage > 80% 2000 (GAVI funds) Coverage > 80% 2001 (GAVI funds) Coverage > 80% 2001 (GAVI funds) >60% Newborns IncidenceIncidence raterate ofof acuteacute hepatitishepatitis BB byby ageage groupgroup priorprior toto vaccinationvaccination (1990)(1990) andand 2000,2000, KazakhstanKazakhstan 200.0 179.9 180.0 160.0 140.0 120.0 96.1 100.0 87.3 100 000 r e 71.7 p 80.0 63.3 60.0 44.0 44.6 47.5 33.3 40.0 27.4 23.7 22.6 17.9 20.0 9.3 11.3 8.2 5.8 2.2 0.6 0.0 < до1 1 1 год 2 года 3-6 лет 7-14 15-19 20-29 30-39 40-49 50-59 60 лет года лет лет лет лет лет лет и Age выше 1990 2000 AcuteAcute HBVHBV incidenceincidence raterate inin 20002000 andand 20052005 inin KazakhstanKazakhstan 200 180 P 160 e r 140 1 120 0 2000 0 100 0 2005 0 80 0 60 0 40 20 0 <1 1-2 3-6 7-14 15-19 20-29 30-39 40-49 50-59 60&> **-- universaluniversal vaccination vaccination since since 1998 1998 ReportedReported AcuteAcute ViralViral HepatitisHepatitis BB amongamong vaccinatedvaccinated children,children, Kazakhstan,Kazakhstan, 20032003--20052005 20032003 –– 44 20042004 –– 00 20052005 –– 55 HepatitisHepatitis BB incidenceincidence amongamong childrenchildren underunder 55,, KyrgyzKyrgyz SentinelSentinel Surveillance,Surveillance, 20002000--20020055 70,0 120 60,0 57,6 100 96 96 50,0 86 80 000 40,0 66 100, % 60 30,0 46 dence per ci 40 n I 20,0 18,8 26 13,6 20 10,0 10,2 10,2 8,7 0,0 0 2000 2001 2002 2003 2004 2005 HBV infection (anti-HBc total) and chronic HBV infection (HBsAg) among HB-immunized and non-immunized children, Almaty, Kazakhstan, 2001 16,0 14,3 14,0 12,0 10,0 % HBsAG 8,0 % aHBcor-total 6,0 4,8 4,0 2,0 1,2 0,0 0,0 1998-2000 1995-1997 1993-1994 (не (новорожNewbornsденные) (пCatchривит ыupе 6п-7р ивитyearsы oldе) "вдvaccinationогонку") unvaccinated N=351 P1-2 <0.001 Anti-HBs among HB-immunized and non- immunized children, Almaty, Kazakhstan/ 2001 99,1% 92,4% 100 88,1% 90 80 70 60 50 40 1 1 2 дозы 30 20 9,6% 10 0 2 1998-2000 1996-1997 1995 1993-1994 1-3 years old новnewbornsорожденные 1, 3 года 5 years(5 леoldт) 6-67- ле7 тyears, неприв oldитые unvaccinated Catchвдогонку up vaccination P1-2 <0.001 N=351 HepatitisHepatitis BB vaccinevaccine effectivenesseffectiveness study,study, KyrgyzstanKyrgyzstan,, 20052005 DesignDesign -- CohortCohort StudyStudy ExposedExposed groupgroup –– vaccinatedvaccinated childrenchildren 33--55 yearsyears ofof ageage UnexposedUnexposed groupgroup –– unvaccinatedunvaccinated childrenchildren 77--99 yearsyears ofof ageage SourceSource ofof exposureexposure datadata –– medicalmedical recordsrecords onon HepBHepB vaccinationvaccination OutcomeOutcome measuremeasure –– lablab teststests forfor HBsAgHBsAg andand totaltotal antianti--HBcHBc HepatitisHepatitis BB VaccineVaccine EffectivenessEffectiveness inin PreventionPrevention ofof ChronicChronic HepatitisHepatitis B,B, KyrgyzstanKyrgyzstan,, 20052005 HBsAg + HBsAg - Total Attack rate (%) Vaccinated 2 468 470 0.4 Unvaccinated 11 488 499 2.2 Total 13 956 969 1.3 RR = 0.2 (0.04 – 0.9) P<0.05 VE = 80.6% (13.4 – 95.7) P<0.05 HepatitisHepatitis BB VaccineVaccine EffectivenessEffectiveness iinn PreventionPrevention ofof HepatitisHepatitis BB Infection,Infection, KyrgyzstanKyrgyzstan,, 20052005 IgG IgG Total Attack antiHBC + antiHBC - rate (%) Vaccinated 9 461 470 0.4 Unvaccinated 52 447 499 2.2 Total 61 908 967 1.3 RR = 0.2 (0.09 – 0.4) P<0.05 VE = 81.6% (63.1 – 90.8) P<0.05 ConclusionConclusion 11 ViralViral hepatitishepatitis havehave presentedpresented andand remainremain aa significantsignificant threatthreat toto thethe publicpublic healthhealth inin thethe countriescountries ofof CentralCentral AsiaAsia HBsAgHBsAg routineroutine infantinfant immunizationimmunization isis thethe mostmost effectiveeffective strategystrategy forfor HBVHBV,, HDVHDV preventionprevention inin thethe regionregion MoreMore thenthen 80%80% ofof casescases ofof ChronicChronic HepatitisHepatitis B,B, andand HepatitisHepatitis BB infectioninfection wouldwould havehave occurredoccurred amongamong thethe vaccinatedvaccinated groupgroup hadhad theythey notnot beenbeen vaccinated,vaccinated, werewere preventedprevented byby HBsAgHBsAg immunizationimmunization ConclusionConclusion 22 EstimateEstimate 1010 000000 liveslives werewere savedsaved perper yearyear byby implementationimplementation ofof regionalregional ViralViral HepatitisHepatitis BB preventionprevention programprogram ProgramProgram implementationimplementation isis aa crucialcrucial elementelement ofof capacitycapacity buildingbuilding inin thethe areaarea ofof infectiousinfectious diseasesdiseases surveillance,surveillance, prevention,prevention, andand controlcontrol throughthrough anan integratedintegrated approachapproach ofof epidemiologicalepidemiological andand laboratorylaboratory strengtheningstrengthening SustainableSustainable programsprograms positivelypositively impactimpact thethe healthhealth ofof thethe regionregion andand serveserve toto decreasedecrease thethe burdenburden ofof infectiousinfectious diseasesdiseases.