erinatal-Hepatitis-B-Prevention-ProgramTX-Department-of：围产期乙型肝炎预防programtx部课件

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/?/PrenatalPerin

2、atalPostnatal05/11/2010Rates 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 immuno

3、prophylaxis ? 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 infectionHepatitis B infection has a long incubation period* between exposure and disease; provides

4、 “window” for 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 InfectionHBsAg = Hepatitis B surface antigen, marker of acute or chronic infection (infectious)HBeAg =Hepa

5、titis B e antigen, marker of high level active HBV replication (highly infectious)Serostatus of Mother % Infants InfectedHBsAgPositivePositiveHBeAgPositiveNegative70% - 90% Highest risk 5% - 20% Lower risk05/11/2010OverviewACIP recommendations for immunoprophylaxis to prevent perinatal hepatitis B i

6、nfectionHepatitis B vaccines for infantsSafetyEfficacy with and without HBIGEfficacy in preterm infantsRevaccinating non-responders05/11/2010Case Management toPrevent Perinatal HBV Infection-1(Post-exposure Prophylaxis-PEP) Identify all HBsAg-positive women and case manage their infantsEnsure their

7、infants receive hepatitis B vaccine and HBIG 12 hours of birthSituation A-Highest Risk Infants05/11/2010Case Management toPrevent Perinatal HBV Infection-2(Post-exposure Prophylaxis-PEP) Complete the recommended primary series of hepatitis B vaccineBW 2000 gm: 3-4 total doses of hepatitis B vaccineB

8、W 2000 gm (preterm infants): 4 total doses hepatitis B vaccine05/11/2010Case Management to Prevent Perinatal HBV Infections-3(Post-exposure Prophylaxis-PEP) 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 c

9、an give positive result (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) Post-vaccination serologic te

10、sts and their interpretationAnti-HBs 10 mIU/ml = immuneHBsAg, 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 Infecti

11、ons-5(Post-exposure Prophylaxis-PEP) Post-vaccination serology #1, CtdIf HBsAg-negative and anti-HBs 10 mIU/ml, the infant is still susceptibleRevaccinate with 3 more doses hepatitis B vaccine (starting as soon as possible)05/11/2010Case Management to Prevent Perinatal HBV Infections- 6(Post-exposur

12、e Prophylaxis-PEP) 1-2 months after last revaccination dose, check another post-vaccination serology (# 2) Immune - Anti-HBs 10 mIU/ml, Infected HBsAg-positive, orRemains susceptible (non-responder) - anti-HBs 2000 gm: HBIG 7 days if mothers HBsAg test positiveCase manage infant unless HBsAg-negativ

13、e05/11/2010Immunoprophylaxis to Prevent Perinatal HBV Infections-8(Post-exposure Prophylaxis-PEP) Infants born to woman with negative HBsAg at birthing hospitalEncourage hospitals to adopt universal “birth dose” policyFirst dose hepatitis B vaccine before hospital dischargeSafety net HBsAg-positive

14、contacts, errorsSituation C- Most InfantsFirst Generation Hepatitis B Vaccines Plasma Derived Commercially available in 1982Consisted of purified HBsAg (protein) from adults with chronic HBV infection; vaccine preparations treated to inactivate virusesHighly effective (90%)Concerns about transmittin

15、g blood borne pathogens; discontinued 1990 05/11/2010Second Generation Hepatitis B Vaccines Recombinant DNA Introduced 1986Genetic sequences of HBsAg protein (S gene) “copied” into yeast cells, expressed HBsAg protein, purified to remove yeast cell products Adjuvant aluminum (hydroxide, phosphate)Th

16、imerosal preservative-free since March 2000 05/11/2010Safety of Hepatitis B Vaccine1 billion doses administered globallyNo increase in temperature, no increase in fever/sepsis “work-ups” after a birth doseOlder infants, children local pain at injection site, 3% - 29% Low grade temperature (37.7oC),

17、1% -6%Serious adverse reactions extremely rare05/11/2010Multiple vaccine trials among infants.& children Hepatitis B Vaccine is SafeDoes not cause Sudden Infant Death Syndrome (SIDS)ArthritisGuillain-Barr, brachial neuritisDemyelinating diseases (optic neuritis, multiple sclerosis, transverse myelit

18、is, acute disseminated encephalomyelitis, etc) 05/11/2010Institute 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 al

19、l doses in hepatitis B vaccine series, including a dose at birthVaccines interchangeable in series05/11/20102 Combination Vaccines with Hepatitis B, for Infants and ChildrenGSK, 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

20、 6 weeks and older (NOT for birth dose; poor responses to DTaP, Hib)Not interchangeable except with monovalent hepatitis B vaccines05/11/2010Hepatitis B Vaccination Schedulesfor Infants: 3 or 4 DosesFirst 2 doses provide early protection Booster (last) dose given at a minimum age 24 weeks, adds long

21、-term protection Delayed doses do not need to be repeated but.Risk of infection continues during delay05/11/2010Hepatitis B Vaccination3 Dose Schedules for InfantsACIP recommended schedules (if mother HBsAg-negative)BW 2000 gm: age 0 (before hospital discharge), 1-2 & 6-18 monthsBW 2000 gm (preterm)

22、: at hospital discharge or age 1 month, 2-4 & 6-18 monthsOther schedules: age 0-2, 1-4, 6-18 months 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 dosesMonovalent HepB

23、vaccine at birth + 3 doses combination vaccine 2, 4, 6 monthsBW 2000 gm (preterm) born to HBsAg-positive or 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 Prev

24、ent Perinatal Hepatitis B InfectionHepatitis B immune globulin (HBIG)Hepatitis B vaccine with and without HBIG Hepatitis B vaccine responses in preterm infantsProtection for non-responders by revaccination05/11/2010HBIG (alone) to Prevent Perinatal HBV Infection among Infants born to HBeAg-Positive

25、Women, Taiwan, 1978-1982Type of ProphylaxisSchedule Age (Months)No. InfantsChronic HBV Age 15 Mo.Placebo (Saline) 1.0 mlBirth, 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 deliv

26、ery room, 95% 1hr05/11/2010Infants (%) 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 WomenHBIG temporarily protected infants from hepatitis B virus infectionMore infected infants develop

27、ed active response (immunity) to HBV infection than chronic infectionReduced 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 WomenVaccine efficacy defined as perce

28、nt protected against chronic HBV infection in first year of lifeHistorical 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

29、S, 2004, 200905/11/2010Hepatitis B Vaccine Trials Infants Born to HBeAg-Positive WomenPlasma and recombinant vaccinesDosages 2.5 - 20 g HBsAg protein RegimensFirst dose 24 hours (3-5 days) of lifeMany schedules: 0, 1, 6 months; 0,1,2,12 months; 0, 1.5, 9 months, etc)With/without HBIG 94*41377* GSK 1

30、0 ug6455100 92*180229 05/11/2010*Measured at age 9 monthsSeroprotection and ImmunogenicityImmunogenicity and seroprotection rates improve with booster dose (# 3)Higher geometric mean titer (GMT) extends period of measureable antibodySeroprotection achieved among 90+% infants after 3 doses hepatitis

31、B vaccine5-10% infants non-responding; benefit 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%

32、Netherlands1992Plasma -10 DNA- 20705-93 - 4100%Italy-1998GSK-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 Mic

33、robiolImmunol 1997. Seroprotection Rates among Infant “Non-responders”after RevaccinationSeroprotection rates achieved among 85%-95% of infant vaccine non-responders after revaccinationImproved response likely tied to older ageUse monovalent hepatitis B vaccine and routine dosage; effective, and avo

34、ids unnecessary doses of other components in combination vaccines05/11/2010Hepatitis B Vaccine for Low Birth Weight (Preterm) InfantsNo 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 high