1、Perinatal Hepatitis B Prevention ProgramTX Department of Health ServicesTrudy Murphy,MDPrevention BranchDivision of Viral HepatitisNCHHSTP/CDCMay 11,2010Immunoprophylaxis againstHepatitis B Virus Infection05/11/2010Pathways for Transmission to Infants of Hepatitis B Virus Infection/?/PrenatalPerinat
2、alPostnatal05/11/2010Rates of Symptomatic and Chronic HBV Infection by Age at InfectionAge at infectionAcute HBV(symptomatic)Chronic HBV 1 year5 years20 50%6 10%McMahon BJ J Infect Dis 1985;151:599Edmonds WJ Proc R Soc Lond B Biol Sc 1993;253:197Hyams KC.Clin Infect Dis 1995;20:992What is immunoprop
3、hylaxis?A form of post-exposure prophylaxis(PEP)using hepatitis B vaccine and high titer hepatitis B immune globulin(HBIG)to prevent perinatal and postnatal transmission of hepatitis B virus infection Hepatitis B infection has a long incubation period*between exposure and disease;provides“window”for
4、 protecting against infection05/11/2010*90 days range 60-150 days05/11/2010Risk of Perinatal HBV Transmission Varies by Degree of Virus Replication amongPregnant Women with Chronic Infection HBsAg=Hepatitis B surface antigen,marker of acute or chronic infection(infectious)HBeAg=Hepatitis B e antigen
5、,marker of high level active HBV replication(highly infectious)Serostatus of Mother%Infants InfectedHBsAgPositivePositiveHBeAgPositiveNegative70%-90%Highest risk 5%-20%Lower risk05/11/2010Overview ACIP recommendations for immunoprophylaxis to prevent perinatal hepatitis B infection Hepatitis B vacci
6、nes for infants Safety Efficacy with and without HBIG Efficacy in preterm infants Revaccinating non-responders05/11/2010Case Management toPrevent Perinatal HBV Infection-1(Post-exposure Prophylaxis-PEP)1.Identify all HBsAg-positive women and case manage their infants2.Ensure their infants receive he
7、patitis B vaccine and HBIG 12 hours of birthSituation A-Highest Risk Infants05/11/2010Case Management toPrevent Perinatal HBV Infection-2(Post-exposure Prophylaxis-PEP)3.Complete the recommended primary series of hepatitis B vaccine BW 2000 gm:3-4 total doses of hepatitis B vaccine BW 2000 gm(preter
8、m infants):4 total doses hepatitis B vaccine05/11/2010Case Management to Prevent Perinatal HBV Infections-3(Post-exposure Prophylaxis-PEP)4.1-2 months after last dose,obtain“post-vaccination serology”(#1)Wait at least 1 month after last dose:antigen from last dose of vaccine can give positive result
9、(18 days)Obtain serology as soon as possible but at least 9 months after last dose:some infants will be susceptible and will benefit from revaccination05/11/2010Case Management to Prevent Perinatal HBV Infections-4(Post-exposure Prophylaxis-PEP)4.Post-vaccination serologic tests and their interpreta
10、tion Anti-HBs 10 mIU/ml=immune HBsAg,if positive=HBV infected Educate to prevent HBV transmission and complete contact management for members of the household(screening,vaccination,referring for evaluation,care)05/11/2010Case Management to Prevent Perinatal HBV Infections-5(Post-exposure Prophylaxis
11、-PEP)4.Post-vaccination serology#1,CtdIf HBsAg-negative and anti-HBs 10 mIU/ml,the infant is still susceptible5.Revaccinate with 3 more doses hepatitis B vaccine(starting as soon as possible)05/11/2010Case Management to Prevent Perinatal HBV Infections-6(Post-exposure Prophylaxis-PEP)6.1-2 months af
12、ter last revaccination dose,check another post-vaccination serology(#2)Immune-Anti-HBs 10 mIU/ml,Infected HBsAg-positive,or Remains susceptible(non-responder)-anti-HBs 2000 gm:HBIG 7 days if mothers HBsAg test positive Case manage infant unless HBsAg-negative05/11/2010Immunoprophylaxis to Prevent Pe
13、rinatal HBV Infections-8(Post-exposure Prophylaxis-PEP)1.Infants born to woman with negative HBsAg at birthing hospital2.Encourage hospitals to adopt universal“birth dose”policyFirst dose hepatitis B vaccine before hospital dischargeSafety net HBsAg-positive contacts,errorsSituation C-Most InfantsFi
14、rst Generation Hepatitis B Vaccines Plasma Derived Commercially available in 1982 Consisted of purified HBsAg(protein)from adults with chronic HBV infection;vaccine preparations treated to inactivate viruses Highly effective(90%)Concerns about transmitting blood borne pathogens;discontinued 1990 05/
15、11/2010Second Generation Hepatitis B Vaccines Recombinant DNA Introduced 1986 Genetic sequences of HBsAg protein(S gene)“copied”into yeast cells,expressed HBsAg protein,purified to remove yeast cell products Adjuvant aluminum(hydroxide,phosphate)Thimerosal preservative-free since March 2000 05/11/20
16、10Safety of Hepatitis B Vaccine 1 billion doses administered globally No increase in temperature,no increase in fever/sepsis“work-ups”after a birth dose Older infants,children local pain at injection site,3%-29%Low grade temperature(37.7oC),1%-6%Serious adverse reactions extremely rare05/11/2010Mult
17、iple vaccine trials among infants.&children Hepatitis B Vaccine is Safe Does not cause Sudden Infant Death Syndrome(SIDS)Arthritis Guillain-Barr,brachial neuritis Demyelinating diseases(optic neuritis,multiple sclerosis,transverse myelitis,acute disseminated encephalomyelitis,etc)05/11/2010Institute
18、 of Medicine Report 20022 Monovalent Recombinant Hepatitis B B Vaccines for Infants and Children MSD,Recombivax-HB,5 g/0.5 ml dose(1986)GSK,Engerix-B,10 g/0.5 ml dose(1989)Both administered intramuscular route(IM)Approved for all doses in hepatitis B vaccine series,including a dose at birth Vaccines
19、 interchangeable in series05/11/20102 Combination Vaccines with Hepatitis B,for Infants and Children GSK,Pediarix(DTaP-IPV-HepB),HepB 10 g/0.5 ml dose(2002)MSD,Comvax(Hib-HepB),HepB 5 g/0.5 ml dose(1996)Approved for ages 6 weeks and older(NOT for birth dose;poor responses to DTaP,Hib)Not interchange
20、able except with monovalent hepatitis B vaccines05/11/2010Hepatitis B Vaccination Schedulesfor Infants:3 or 4 Doses First 2 doses provide early protection Booster(last)dose given at a minimum age 24 weeks,adds long-term protection Delayed doses do not need to be repeated but.Risk of infection contin
21、ues during delay05/11/2010Hepatitis B Vaccination3 Dose Schedules for Infants ACIP recommended schedules(if mother HBsAg-negative)BW 2000 gm:age 0(before hospital discharge),1-2&6-18 months BW 2000 gm(preterm):at hospital discharge or age 1 month,2-4&6-18 months Other schedules:age 0-2,1-4,6-18 mont
22、hs EPI(WHO)schedule:ages 6,10,14 weeks(birth dose adopted in some countries)05/11/2010Hepatitis B Vaccination4 Dose Schedules for Infants Safe:no increase in reactions with 4 doses Monovalent HepB vaccine at birth+3 doses combination vaccine 2,4,6 months BW 2000 gm(preterm)born to HBsAg-positive or
23、HBsAg-unknown status women;birth dose given(“not counted”for series)Chronological ages 0,1,2-3,6-7 months05/11/2010MMWR 2005;54(RR-16)Background for Recommended Case Management to Prevent Perinatal Hepatitis B Infection Hepatitis B immune globulin(HBIG)Hepatitis B vaccine with and without HBIG Hepat
24、itis B vaccine responses in preterm infants Protection for non-responders by revaccination05/11/2010HBIG(alone)to Prevent Perinatal HBV Infection among Infants born to HBeAg-Positive Women,Taiwan,1978-1982Type of ProphylaxisSchedule Age(Months)No.InfantsChronic HBV Age 15 Mo.Placebo(Saline)1.0 mlBir
25、th,3&6 6192%HBIG*1.0 ml x 1Birth5754%HBIG 0.5 ml x 3Birth,3&6 6726%05/11/2010Beasley RP.Dev Biol Stand 1982;54:363-375*HBIG=180 mIU/ml Birth dose administered in delivery room,95%1hr05/11/2010PlaceboHBIG 1.0ml X 1HBIG 0.5ml X 30%20%40%60%80%100%03691215Cumulative Onset of Persistent HBsAg(%)Infants
26、Age(months)Infants(%)with Chronic Hepatitis B VirusInfection by Treatment Group and AgeBeasley RP.Dev Biol Stand 1982;54:363-375HBIG Prophylaxis for Infants Born to HBeAg-positive Women HBIG temporarily protected infants from hepatitis B virus infection More infected infants developed active respons
27、e(immunity)to HBV infection than chronic infection Reduced chronic infections by 50%-75%before age 15 months New infections continued05/11/2010Beasley RP.Dev Biol Stand 1982;54:363-375Hepatitis B Vaccine Trials Infants Born to HBsAg-Positive Women Vaccine efficacy defined as percent protected agains
28、t chronic HBV infection in first year of life Historical controls for rates chronic infection,70%,90%Rates of seroprotection(anti-HBsAg 10 mIU/ml)after 3 doses,measured at age 9-12 months;geometric mean titers anti-HBsAgReviewed in:Mast E.Vaccine,Eds.Orenstein W,Plotkin S,2004,200905/11/2010Hepatiti
29、s B Vaccine Trials Infants Born to HBeAg-Positive Women Plasma and recombinant vaccines Dosages 2.5-20 g HBsAg protein Regimens First dose 24 hours (3-5 days)of life Many schedules:0,1,6 months;0,1,2,12 months;0,1.5,9 months,etc)With/without HBIG 94*41377*GSK 10 ug6455100 92*180229 05/11/2010*Measur
30、ed at age 9 monthsSeroprotection and Immunogenicity Immunogenicity and seroprotection rates improve with booster dose(#3)Higher geometric mean titer(GMT)extends period of measureable antibody Seroprotection achieved among 90+%infants after 3 doses hepatitis B vaccine 5-10%infants non-responding;bene
31、fit from revaccination05/11/2010Infant Seroprotection(SP)Rates after Revaccination with Hepatitis B Vaccine(HBsAg-Positive or-Negative Women)CountryVaccine1o SeriesNo.InfantsSP Rate1o SeriesNo.Infants#Doses%10 mIU/ml anti-HBsAgIran-2005-21380%34294%Netherlands1992Plasma-10 DNA-20705-93-4100%Italy-19
32、98GSK-10180598%38295%Iran-2008DNA 2.5,5,10138096%48183%Iran-1997GSK-10117693%221-291%05/11/2010Roushan MRH.Eur J Elin Microbiol Infect Dis 2005;del Canho R.Vaccine 1992;Belloni C.Vaccine 1998;Jafarzadeh A.Vaccine 2008;Shokri F.Med MicrobiolImmunol 1997.Seroprotection Rates among Infant“Non-responder
33、s”after Revaccination Seroprotection rates achieved among 85%-95%of infant vaccine non-responders after revaccination Improved response likely tied to older age Use monovalent hepatitis B vaccine and routine dosage;effective,and avoids unnecessary doses of other components in combination vaccines05/
34、11/2010Hepatitis B Vaccine for Low Birth Weight(Preterm)Infants No special adverse reactions(monitor for apnea as needed)LBW infants(BW 12 hr associated with higher rates perinatal HBV infection Dose 2 delayed to age 10 weeks,associated with higher rate perinatal hepatitis B infection Dose 3(booster
35、)at age 24 weeks improves long-term protection Dose 1 before hospital discharge associated with higher vaccination coverage for other vaccines 05/11/2010Fischer G et al.PIDJ 2009;Yusuf HR et al.JAMA 2000Immunoprophylaxis against Hepatitis B Virus Infection-Summary Hepatitis B vaccines are safe and v
36、ery effective for infants and children Timely completion of case management with hepatitis B vaccine and HBIG prevents 90%-95%chronic HBV infections acquired in the first year of life Revaccination effectively induces protection in 85%-95%of non-responding infants 05/11/2010Immunoprophylaxis to Prev
37、ent Perinatal Hepatitis B Infection(PEP)-Conclusion Preventing chronic HBV infection prevents development of debilitating liver cirrhosis,hepatocellular cancer,and reduces the reservoir of persons transmitting hepatitis B infection Immunoprophylaxis for perinatal infections is life saving and cost-effective05/11/201005/11/2010Thank youAcknowledgements CDC/NCIRD/ISD Lisa Jacques-Carroll CDC/NCHHSTP/DVH Tanja Walker Geoffrey Beckett John Ward Perinatal Hepatitis B Coordinators
