1、Epidemic jaundice described by Hippocrates in 5th century BCJaundice reported among recipients of human serum and yellow fever vaccines in 1930s and 1940sAustralian antigen described in 1965Serologic tests developed in 1970sHepatitis BHepatitis B VirusHepadnaviridae family (DNA)Numerous antigenic co

2、mponentsHumans are only known hostMay retain infectivity for at least 1 month at room temperature200 million carriers worldwideEstablished cause of chronic hepatitis and cirrhosisHuman carcinogen - cause of up to 80% of hepatocellular carcinomasHepatitis B Virus InfectionHBsAgHBcAgHBeAgHepatitis B V

3、irusHepatitis B Clinical FeaturesIncubation period 6 weeks to 6 months (average 120 days)Nonspecific prodrome of fever, malaise, headache, myalgiaIllness not specific for hepatitis BAt least 50% of infections asymptomaticFulminant hepatitisHospitalizationCirrhosisHepatocellular carcinomaDeathHepatit

4、is B ComplicationsChronic Hepatitis B Virus InfectionChronic viremiaResponsible for most mortalityOverall risk 10%Higher risk with early infectionRisk of Chronic HBV Carriage by Age of InfectionHepatitis B EpidemiologyReservoirHuman. EndemicTransmissionBloodborneSubclinical cases transmit Communicab

5、ility1-2 months before and after onset of symptomsChronic carriersHepatitis B Perinatal Transmission*If mother positive for HBsAg and HBeAg70%-90% of infants infected90% of infected infants become chronic carriersIf positive for HBsAg only20% of infants infected90% of infected infants become chronic

6、 carriers*in the absence of postexposure prophylaxisHigh (8%): 45% of global populationlifetime risk of infection 60%early childhood infections commonIntermediate (2%-7%): 43% of global populationlifetime risk of infection 20%-60%infections occur in all age groupsLow (2%): 12% of global populationli

7、fetime risk of infection 1 millionNew carriers 5,000Deathfulminant hepatitis 200liver cancer 1,500cirrhosis 4,000HBV Disease Burden in the United States*1999 estimatesAge of Infection of Acute and Chronic Hepatitis B Virus InfectionAcute infectionChronic infectionCDC Sentinel Sites. 1989 data.Risk F

8、actors for Hepatitis BCDC Sentinel Sites. 1992-1993 data.Hepatitis B Virus Infection by Duration of High Risk Behavior03691215Years at Risk020406080100Percent infectedIV drug userHomosexual menHCWsHeterosexualStrategy to Eliminate Hepatitis B Virus Transmission - United StatesPrevent perinatal HBV t

9、ransmissionRoutine vaccination of all infantsVaccination of children in high-risk groupsVaccination of adolescentsVaccination of adults in high-risk groups1965Discovery of Australian antigen1973Successful HBV infection of chimpanzees1981Licensure of plasma-derived vaccine1986Licensure of recombinant

10、 vaccine1991Universal infant vaccination1996Universal adolescent vaccinationHepatitis B VaccineHepatitis B VaccineCompositionRecombinant HBsAgEfficacy95% (Range, 80%-100%)Duration ofImmunity15 yearsSchedule3 DosesBooster doses not routinely recommended Hepatitis B Vaccine FormulationsRecombivax HB (

11、Merck)- 5.0 mcg/0.5 ml (pediatric)- 10 mcg/1 ml (adult)- 40 mcg/1 ml (dialysis)Engerix-B (GSK)- 10 mcg/0.5 ml (pediatric)- 20 mcg/1 ml (adult)Recommended Dose of Hepatitis B VaccineInfants and children20 yearsRecombivax HBDose (mcg)0.5 ml (5)0.5 ml (5)1.0 ml (10)Engerix-BDose (mcg)0.5 ml (10)0.5 ml

12、(10)1.0 ml (20)Hepatitis B VaccineLong-term EfficacyImmunologic memory established following vaccinationExposure to HBV results in anamnestic anti-HBs responseChronic infection rarely documented among vaccine respondersHepatitis B VaccineRoutine booster doses are NOT routinely recommended for any gr

13、oupHepatitis B Vaccine RecommendationsYear198119911995Recommendation Persons at high riskAll infantsAdolescentsIndications for Hepatitis B VaccineInfantsAdolescents 11-12 years of ageSelected adultsDosePrimary 1Primary 2Primary 3 Usual Age 0-2 months* 1- 4 months6-18 monthsMinimum Interval -1 month2

14、 monthsHepatitis B VaccineRoutine Infant Schedule*ACIP prefers the first dose of hepatitis B vaccine be given soon after birth and before hospital discharge.Third Dose of Hepatitis B VaccineMinimum of 2 months after second dose, andAt least 4 months after first dose, andFor infants, at least 6 month

15、s of ageVery Low Birthweight InfantsInfants 2000 grams respond poorly to vaccine Delay first dose until chronological age 1 month if mother HBsAg negativeBirth dose and HBIG if mother HBsAg positiveCOMVAXHepatitis B-Hib combinationUse when either antigen is indicatedCannot use 6 weeks of ageNot lice

16、nsed for use if mother HBsAg+Hepatitis B VaccineAdolescent VaccinationRoutine vaccination recommended through age 18yearsIntegrate into routine adolescent immunization visitFlexible schedulesDosePrimary 1Primary 2Primary 3 Minimum Interval - 1 month 2 months* Usual Interval -1 month5 monthsHepatitis

17、 B VaccineAdolescent and Adult Schedule*third dose must be separated from first dose by at least 4 monthsAlternative Adolescent Vaccination ScheduleTwo 10 mcg doses of Recombivax HB separated by 4-6 monthsMay only be used for adolescents 11-15 years of ageOnly applies to Merck hepatitis B vaccineAdu

18、lt Hepatitis B Vaccine CandidatesMen who have sex with menHeterosexual with multiple partnersPersons diagnosed with an STDProstitutesInjection drug usersMale prison inmatesPersons receiving dialysisHealth care workersAdult Hepatitis B Vaccine CandidatesStaff of institutions for developmentally disab

19、ledAlaskan Natives, Pacific IslandersImmigrants/refugees* Adoptees, orphans, unaccompanied minors*Household members and sexual partners of HBV carriers Extended travel to areas of high endemicityRecipients of certain blood products*from countries of high or intermediate HBV endemnicityPrevaccination

20、 Serologic TestingNot indicated before routine vaccination of infants or childrenMay be considered when vaccinating adolescents in groups with high rates of HBV infectionAlaskan NativesPacific IslandersChildren of immigrants from endemic countriesFamily members of HBV carriersPostvaccination Serolog

21、ic TestingNot routinely recommended following vaccination of infants, children, adolescents, or most adultsRecommended for:Infants born to HBsAg+ womenDialysis patientsImmunodeficient personsCertain health care workers Postvaccination Serologic TestingHealth care workers who have contact with patients or blood should be tested for antibody after vaccination.Man