1、VIRAL HEPATITIS HISTORICAL PERSPECTIVE,REPORTED CASES OF SELECTED NOTIFIABLE DISEASES PREVENTABLE BY VACCINATION, UNITED STATES, 2001,Hepatitis A Hepatitis B Pertussis Meningococcal disease H. influenzae, invasive Mumps MeaslesSource: NNDSS, CDC,10,609 7,843 7,580 2,333 1,597 266 116,HEPATITIS A VIR
2、US,HEPATITIS A VIRUS,RNA Picornavirus Single serotype worldwide Acute disease and asymptomatic infection No chronic infection Protective antibodies develop in response to infection - confers lifelong immunity,HEPATITIS A - CLINICAL FEATURES,Jaundice by 14 yrs 70%-80% Rare complications: Fulminant he
3、patitis Cholestatic hepatitis Relapsing hepatitis Incubation period: Average 30 days Range 15-50 days Chronic sequelae: None,0,1,2,3,4,5,6,7,8,9,10,11,12,13,Week,Response,Clinical illness,ALT,IgM,IgG,HAV in stool,Infection,Viremia,EVENTS IN HEPATITIS A VIRUS INFECTION,CONCENTRATION OF HEPATITIS A VI
4、RUS IN VARIOUS BODY FLUIDS,Source: Viral Hepatitis and Liver Disease 1984;9-22J Infect Dis 1989;160:887-890,Feces,Serum,Saliva,Urine,100,102,104,106,108,1010,Body Fluids,Infectious Doses per mL,Endemicity,Disease Rate,Peak Age of Infection,Transmission Patterns,Early childhood,Late childhood/ young
5、adults,Young adults,High,Moderate,Low,Very low,Low to high,High,Low,Very low,Adults,Person to person;,outbreaks uncommon,Person to person;,food and waterborne,outbreaks,Person to person;,food and waterborne,outbreaks,GLOBAL PATTERNS OF HEPATITIS A VIRUS TRANSMISSION,GEOGRAPHIC DISTRIBUTION OF HEPATI
6、TIS A VIRUS INFECTION,HEPATITIS A, UNITED STATES,ACUTE HEPATITIS A CASE DEFINITION FOR SURVEILLANCE,Clinical criteria An acute illness with: discrete onset of symptoms (e.g. fatigue, abdominal pain, loss of appetite, intermittent nausea, vomiting), and jaundice or elevated serum aminotransferase lev
7、els Laboratory criteria IgM antibody to hepatitis A virus (anti-HAV) positive Case Classification Confirmed. A case that meets the clinical case definition and is laboratory confirmed or a case that meets the clinical case definition and occurs in a person who has an epidemiologic link with a person
8、 who has laboratory-confirmed hepatitis A (i.e., household or sexual contact with an infected person during the 15-50 days before the onset of symptoms).,Source: NNDSS, CDC,REPORTED CASES OF HEPATITIS A, UNITED STATES, 1952-2002,DISEASE BURDEN FROM HEPATITIS A UNITED STATES, 2001,INCIDENCE OF HEPATI
9、TIS A BY AGE GROUP IN STATES WHERE VACCINATION IS RECOMMENDED & CONSIDERED, 1990-2001,Race/Ethnicity,non-Hispanic,Black,non-Hispanic,White,Total,Rate (per 100,000),Native American/ Alaska Native,Asian,Hispanic,10,20,30,110,120,130,10.3,4.6,5.5,6.4,20.7,121.2,0,HEPATITIS A RATES, BY RACE/ETHNICITY; 1
10、994,NUMBER OF YEARS REPORTED INCIDENCE OF HEPATITIS A EXCEEDED 10 CASES PER 100,000, BY COUNTY, 1987-1997,Close personal contact (e.g., household contact, sex contact, child day-care centers) Contaminated food, water (e.g., infected food handlers) Blood exposure (rare) (e.g., injection drug use, rar
11、ely by transfusion),HEPATITIS A VIRUS TRANSMISSION,RISK FACTORS ASSOCIATED WITH REPORTED HEPATITIS A, 1990-2000, UNITED STATES,Source: NNDSS/VHSP,PREVENTING HEPATITIS A,Hygiene (e.g., hand washing) Sanitation (e.g., clean water sources) Hepatitis A vaccine (pre-exposure) Immune globulin (pre- and po
12、st-exposure),PREPARATION OF INACTIVATED HEPATITIS A VACCINES,Cell culture adapted virus grown in human fibroblastsPurified product inactivated with formalinAdsorbed to aluminum hydroxide adjuvant,Highly immunogenic 97%-100% of children, adolescents, and adults have protective levels of antibody with
13、in 1 month of receiving first dose; essentially 100% have protective levels after second dose Highly efficacious In published studies, 94%-100% of children protected against clinical hepatitis A after equivalent of one dose,HEPATITIS A VACCINES,HEPATITIS A VACCINE EFFICACY STUDIES,HEPATITIS A VACCIN
14、ES,Age Volume 2-Dose Schedule Vaccine (yrs) Dose (mL) (mos) HAVRIX # 2-18 720 (EL.U.*) 0.5 0, 6-1218 1,440 1.0 0, 6-12 VAQTA # 2-18 25 (U*) 0.5 0, 6-1818 50 1.0 0, 6-12 * EL.U. Enzyme-linked immunosorbent assay (ELISA) units * Units # has 2-phenoxyethanol as a preservative # has no preservative,Reco
15、mmended Dosages of Hepatitis A Vaccines,Most common side effects Soreness/tenderness at injection site - 50% Headache - 15% Malaise - 7% No severe adverse reactions attributed to vaccine Safety in pregnancy not determined risk likely low Contraindications - severe adverse reaction to previous dose o
16、r allergy to a vaccine component No special precautions for immunocompromised persons,SAFETY OF HEPATITIS A VACCINE,DURATION OF PROTECTION AFTER HEPATITIS A VACCINATION,Persistence of antibody At least 5-8 years among adults and children Efficacy No cases in vaccinated children at 5-6 years of follo
17、w-up Mathematical models of antibody decline suggest protective antibody levels persist for at least 20 years Other mechanisms, such as cellular memory, may contribute,Decreased antibody concentration: Concurrent administration of IG Presence of passively-transferred maternal antibody Age Chronic li
18、ver disease Decreased seroconversion rate: HIV infection May be related to degree ofimmunosuppression Liver transplantation,FACTORS ASSOCIATED WITH DECREASED IMMUNOGENICITY TO HEPATITIS A VACCINE,USE OF HEPATITIS A VACCINE FOR INFANTS,Safe and immunogenic for infants without maternal antibody Presen
19、ce of passively-acquired maternal antibody blunts immune response all respond, but with lower final antibody concentrations Age by which maternal antibody disappears is unclear still present in some infants at one year probably gone in vast majority by 15 months,Approved by the FDA in United States
20、for persons 18 years old Contains 720 EL.U. hepatitis A antigen and20 g. HBsAg Vaccination schedule: 0,1,6 months Immunogenicity similar to single-antigen vaccines given separately Can be used in persons 18 years old who need vaccination against both hepatitis A and B Formulation for children availa
21、ble in many other countries,COMBINED HEPATITIS A HEPATITIS B VACCINE,Considerations: cost of vaccine cost of serologic testing (including visit) prevalence of infection impact on compliance with vaccination Likely to be cost-effective for: persons born in high endemic areas Older U.S. born adults Ol
22、der adolescents and young adults in certain groups (e.g., Native Americans, Alaska Natives, Hispanics, IDUs),PRE-VACCINATION TESTING,High response rate among vaccinees Commercially available assay not sensitive enough to detect lower (protective) levels of vaccine-induced antibody,POST-VACCINATION T
23、ESTING,Not recommended:,Pre-exposure travelers to intermediate and high HAV-endemic regions Post-exposure (within 14 days) Routine household and other intimate contacts Selected situations institutions (e.g., day-care centers) common source exposure (e.g., food prepared by infected food handler),HEP
24、ATITIS A PREVENTION IMMUNE GLOBULIN,ACIP RECOMMENDATIONS FOR PREVENTION OF HEPATITIS A USING HEPATITIS A VACCINE,HEPATITIS A VACCINATION RECOMMENDATIONS: GUIDING PRINCIPLES,Need comprehensive strategy to reduce overall rates Routine vaccination of children likely to be most effective Need creative a
25、pproaches Formulation not available that would allow integration into infant schedule,INCREMENTAL IMPLEMENTATION OF ROUTINE HEPATITIS A VACCINATION OF CHILDREN,1996 - Children living in communities with the highest rates 1999- Children living in states/communities with consistently elevated rates du
26、ring “baseline period” All children nationwide,Reported Hepatitis A Cases, By Year Northern Plains Indian Reservation South Dakota, 1968-2002,* Estimated first dose coverage (children 2-12 years) = 71% * 2002 Preliminary data Counties: Bennett, Corson, Dewey, Jackson, Roberts, Shannon, Todd, Ziebach
27、* Source: South Dakota Department of Health,Vaccination program*,*,HEPATITIS A INCIDENCE UNITED STATES AND NATIVE AMERICANS 1990-2001,Source: NNDSS, CDC,Vaccine Licensed,ACIP Recommendation,Native American,United States,1999 RECOMMENDATIONS FOR HEPATITIS A VACCINATION OF CHILDREN STRATEGY,Further in
28、cremental step Not the same everywhere in the country Regional recommendations using rate-based criteria during a “baseline period” Flexible implementation strategies Children or adolescents One or more single age cohorts Selected settings, e.g., day-care,INCIDENCE OF HEPATITIS A BY REGION, UNITED S
29、TATES, 1966-1997,1999 ACIP RECOMMENDATIONS FOR ROUTINE HEPATITIS A VACCINATION OF CHILDREN,Children Who Should be Routinely Vaccinated- living in states, counties, and communities where the average hepatitis A rate was 20 cases/100,000 during baseline period.Children Who Should be Considered for Rou
30、tine Vaccination- living in states, counties, and communities where the average hepatitis A rate was 20 but 10 cases/100,000 during the baseline period.,Rate 20/100,000* Recommended,Rate 10-20/100,000* Considered,Rate 10/100,000* Not statewide,1999 ACIP RECOMMENDATIONS FOR STATEWIDE ROUTINE HEPATITI
31、S A VACCINATION OF CHILDREN,* Based on average incidence rate during baseline period (1987- 97),Hepatitis A Incidence, United States,1980-2002*,*2002 rate provisional,Incidence of Hepatitis A by U.S. Region, 1990-2002*,86%,89%,50%,*2002 rate provisional,DOSES OF PEDIATRIC HEPATITIS A VACCINE PURCHAS
32、ED BY PUBLIC SECTOR BY U.S. REGION, 1995-2002,Summary of Hepatitis A Incidence by Region: Baseline, 2001, and 2002,% Baseline Cases,% Cases 2001,Rate/100,000,Baseline,2001,2002*,*2002 rate provisional,1987-97 average incidence,2002 incidence,Hepatitis A Incidence,TOP 10 STATES WITH THE HIGHEST HEPAT
33、ITIS A RATES,NOW,2001,THEN,1987,-,1997,HEPATITIS A RATE, BY AGE AND GENDERUNITED STATES, 1990,Age,60+,55-59,50-54,45-49,40-44,35-39,30-34,25-29,20-24,15-19,10-14,5-9,5,Female,Male,11.9,10.1,26.7,26.7,17.2,17.7,14.1,12.8,20.4,16.1,22.2,15.8,17.7,11.4,13.5,7.9,10.3,6.4,7.7,5.6,5.9,4.4,5.9,3.8,3.4,2.8,
34、Rate,Female,Male,Age,60+,55-59,50-54,45-49,40-44,35-39,30-34,25-29,20-24,15-19,10-14,5-9,5,2.5,2.2,4.7,4.7,3.6,3.5,3.4,2.8,6.3,3.8,7.5,3.6,9.3,2.8,8.7,2.3,6.1,2.1,5.6,2.2,5.2,2.6,3.6,2.4,2.8,2.4,HEPATITIS A RATE, BY AGE AND GENDER UNITED STATES, 2001,Rate,HEPATITIS A INCIDENCE BY GENDER, UNITED STAT
35、ES, 1990-2001,0,2,4,6,8,10,12,14,16,18,1990,1991,1992,1993,1994,1995,1996,1997,1998,1999,2000,2001,0,0.2,0.4,0.6,0.8,1,1.2,1.4,1.6,1.8,2,Male,Female,Ratio,Cases per 100,000,Year,Male : Female Rate Ratio,ACIP RECOMMENDATIONS PERSONS AT INCREASED RISK OF INFECTION, 1996,Men who have sex with men Illeg
36、al drug users International travelers Persons who have clotting factor disorders Persons with chronic liver disease,STD Treatment Guidelines MMWR May 10, 2002 51(RR06),“Vaccination against hepatitis is the most effective means of preventing sexual transmission of hepatitis A and B.”,Integration of s
37、ervices for high-risk adults,Reports of converging epidemics (STD, HIV, hepatitis) impacting MSM, IDU, and others at risk Integration of services that target MSM, IDU, and others at risk saves $ and improves services,Lack of integrated prevention activities leads to,Individuals infected with HIV, he
38、patitis and other STDs remain undiagnosed, untreated and uninformedInfected and uninformed have higher levels of risky behavior and continue to transmit Counseling is mistakenly based on limited diagnosis and individuals at risk for HAV and HBV dont get immunized,HEPATITIS A IN THE UNITED STATES -20
39、02,National rate lowest yet recorded Continued monitoring needed to determine if low rates sustained and due to vaccination Evaluation of age-specific rates to assess impact of vaccination strategy Rates increasing in some states Occurring among adults in high risk groups (e.g. MSM, drug users),HEPATITIS A VACCINATION IN THE UNITED STATES CHALLENGES FOR THE FUTURE,Continue implementation of the current recommendations for vaccination of children Sustain vaccination in face of falling ratesFurther reduce incidence Vaccination of high-risk adults Vaccination of children nationwide,
