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Epidemiology and Prevention of Viral Hepatitis A to E:. Hepatitis Branch Centers for Disease Control and Prevention. An Overview. Viral Hepatitis - Historical Perspective. Enterically transmitted. “Infectious”. A. E. Viral hepatitis. NANB. Parenterally transmitted. B. D. C.

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Epidemiology and Prevention of Viral Hepatitis A to E:


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    1. Epidemiology and Prevention of Viral Hepatitis A to E: Hepatitis Branch Centers for Disease Control and Prevention An Overview

    2. Viral Hepatitis - Historical Perspective Enterically transmitted “Infectious” A E Viral hepatitis NANB Parenterally transmitted B D C “Serum” F, G, ? other

    3. Viral Hepatitis - Overview Type of Hepatitis A B C D E Source of feces blood/ blood/ blood/ feces virus blood-derived blood-derived blood-derived body fluids body fluids body fluids Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral transmission permucosal permucosal permucosal Chronic no yes yes yes no infection Prevention pre/post- pre/post- blood donor pre/post- ensure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification

    4. Acute Viral Hepatitis by Type, United States, 1982-1993 34% 47% 16% Hepatitis A Hepatitis B Hepatitis C 3% Hepatitis Non-ABC Source: CDC Sentinel Counties Study on Viral Hepatitis

    5. Estimates of Acute and Chronic DiseaseBurden for Viral Hepatitis, United States HAV HBV HCV HDV Acute infections (x 1000)/year* 125-200 140-320 35-180 6-13 Fulminant deaths/year 100 150 ? 35 Chronic 0 1-1.25 3.5 infections million million 70,000 Chronic liver disease deaths/year 0 5,000 8-10,000 1,000 * Range based on estimated annual incidence, 1984-1994.

    6. Hepatitis A Virus

    7. Hepatitis A - Clinical Features • Incubation period: Average 30 days • Range 15-50 days • Jaundice by <6 yrs, <10%age group: 6-14 yrs, 40%-50% >14 yrs, 70%-80% • Complications: Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis • Chronic sequelae: None

    8. Age-specific Mortality Due to Hepatitis A Age group Case-Fatality (years) (per 1000) <5 3.0 5-14 1.6 15-29 1.6 30-49 3.8 >49 17.5 Total 4.1 Source: Viral Hepatitis Surveillance Program, 1983-1989

    9. Hepatitis A Virus Infection Typical Serologic Course Symptoms Total anti-HAV ALT Titer Fecal HAV IgM anti-HAV 4 5 6 12 24 0 1 2 3 Months after Exposure

    10. Concentration of Hepatitis A Virusin Various Body Fluids Feces Body Fluid Serum Saliva Urine 102 104 100 106 108 1010 Infectious Doses per ml Source: Viral Hepatitis and Liver Disease 1984;9-22 J Infect Dis 1989;160:887-890

    11. Hepatitis A Virus Transmission • Close personal contact(e.g., household contact, sex contact, child day care centers) • Contaminated food, water(e.g., infected food handlers, raw shellfish) • Blood exposure (rare)(e.g., injecting drug use, transfusion)

    12. Incidence of Hepatitis A, United States, 1952-1993 40 30 Rate (per 100,000) 20 10 0 1952 1960 1970 1980 1990 Year Source: CDC, National Notifiable Diseases Surveillance System

    13. Age-specific Incidence of Hepatitis A United States, 1983-93 25 20 15 5-14 years Reported Cases (per 100,000) 15-24 years 25-39 years 10 0-4 years 5 40+ years 0 1983 1984 1985 1987 1988 1989 1990 1991 1992 1993 1986 Year Source: CDC, National Notifiable Diseases Surveillance System

    14. Sources of Hepatitis A Virus Infection byMutually Exclusive Groups, United States, 1983-93 40 30 Personal contact Percentage of Cases 20 Day care center 10 Foreign travel Drug use Outbreak 0 1985 1987 1988 1989 1990 1991 1992 1993 1983 1984 1986 Year Source: CDC, Viral Hepatitis Surveillance Program

    15. Global Patterns of Hepatitis A Virus Transmission Disease Peak Age Endemicity Rate of Infection Transmission Patterns High Low to Early Person to person; High childhood outbreaks uncommon Moderate High Late Person to person; childhood/ food and waterborne young adults outbreaks Low Low Young adults Person to person; food and waterborne outbreaks Very low Very low Adults Travelers; outbreaks uncommon

    16. Geographic Distribution of HAV Infection Anti-HAV Prevalence High Intermediate Low Very Low

    17. Hepatitis A Vaccine Efficacy Studies Vaccine Site/Age Efficacy Vaccine Group N (95% CI) Ò HAVRIX Thailand 38,157 94% (SKB) 1-16 yrs (79%-99%) 2 doses 360 EL.U. ä VAQTA New York 1,037 100% (Merck) 2-16 yrs (85%-100%) 1 dose 25 units JAMA 1994;271:1363-4 N Engl J Med 1992;327:453-7

    18. Hepatitis A Vaccination Strategies Epidemiologic Considerations • Many cases occur in community-wide outbreaks • no risk factor identified for most cases • highest attack rates in 5-14 year olds • children serve as reservoir of infection • Persons at increased risk of infection • travelers • homosexual men • injecting drug users

    19. Routine Childhood Hepatitis A Vaccination • Benefits • established delivery system • vaccination before risk period • potential to interrupt transmission • Unresolved issues/considerations • immunogenicity in infants • development of combination vaccines • duration of protection • cost-effectiveness

    20. ACIP Recommendations - Hepatitis A Vaccine Preexposure Vaccination • Persons at increased risk for infection • travelers to intermediate and high HAV-endemic countries • homosexual and bisexual men • drug users • persons with chronic liver disease • Communities with high rates of hepatitis A(e.g., Alaska Natives, American Indians) • routine childhood vaccination

    21. Features of Community-wide Hepatitis A Outbreaks Usual Age Annual Type of Anti-HAV of Case- Incidence/ Outbreak Community Prevalence patients 100,000 Periodicity Populations High rate <5 yrs old 5-14 yrs 700-1000 5-10yrs well defined 30%-40% geographically >15 yrs old or ethnically 70% -100% Intermediate <5 yrs old 5-29 yrs 50-200 may be less defined rate 10%-25% periodic than in >15 yrs old high-rate <50% communities

    22. ACIP Recommendations - Hepatitis A Vaccine Control of Community-wide Outbreaks High-rate communities • Routine vaccination of young children • Accelerated catch-up vaccination of older children

    23. ACIP Recommendations - Hepatitis A Vaccine Control of Community-wide Outbreaks Intermediate-rate communities • Targeted vaccination can be considered for groups or areas with highest disease rates(e.g., specific age groups, census tracts,drug users) • Factors to consider: • feasibility of vaccinating target groups • program cost • ability to sustain vaccination of young children

    24. ACIP Recommendations - Hepatitis A Vaccine Prevaccination Testing • Considerations: • cost of vaccine • cost of serologic testing (including visit) • prevalence of infection • impact on compliance with vaccination • Likely to be cost-effective for: • adults born, or who lived in, high endemic areas • adults >40 years of age • older adolescents and young adults in certain groups(American Indians, Alaska Natives, Pacific Islanders)

    25. ACIP Recommendations - Hepatitis A Vaccine Postvaccination Testing • Not recommended because of the high response rate among vaccinees • No commercially available test to measure vaccine response

    26. Recommended Doses and Schedules of Hepatitis A Vaccine HAVRIXâ Doses No. Schedule Group Age Doses EL.U.* (ml) (months) Children and 3 360 (0.5) 0, 1, 6-12 adolescents 2-18 years Adults >18 years 2 1,440 (1.0) 0, 6-12 *ELISA units

    27. Hepatitis A Prevention - Immune Globulin • Preexposure • travelers to intermediate and high HAV-endemic regions • Postexposure (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)

    28. Hepatitis B Virus

    29. Hepatitis B - Clinical Features • Incubation period: Average 60-90 days • Range 45-180 days • Clinical illness (jaundice): <5 yrs, <10%³5 yrs, 30%-50% • Acute case-fatality rate: 0.5%-1% • Chronic infection: <5 yrs, 30%-90%³5 yrs, 2%-10% • Premature mortality fromchronic liver disease: 15%-25%

    30. Acute Hepatitis B Virus Infection with Recovery Typical Serologic Course Symptoms anti-HBe HBeAg Total anti-HBc Titer anti-HBs IgM anti-HBc HBsAg 0 4 8 12 16 24 28 32 52 100 20 36 Weeks after Exposure

    31. Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course Acute (6 months) Chronic (Years) HBeAg anti-HBe HBsAg Total anti-HBc Titer IgM anti-HBc Years 0 4 8 16 20 24 28 36 12 32 52 Weeks after Exposure

    32. Rate of Reported Hepatitis B by Age Group United States, 1990 25 20 15 Rate (per 100,000) 10 5 0 0-14 15-19 20-29 30-39 40+ Age Group (Years) Source: CDC Viral Hepatitis Surveillance Program

    33. Age at Aquisition of Acute and Chronic HBV Infection United States, 1989 Estimates (4% ) Perinatal (24%) (4%) Children (12%) (1-10 yrs) (8%) Adolescent (6%) Adult (59%) Adult (83%) Acute HBV Infections Chronic HBV Infections

    34. Outcome of Hepatitis B Virus Infection by Age at Infection 100 100 80 80 60 60 Chronic Infection Symptomatic Infection (%) Chronic Infection (%) 40 40 20 20 Symptomatic Infection 0 0 1-6 months 7-12 months Older Children and Adults Birth 1-4 years Age at Infection

    35. Global Patterns of Chronic HBV Infection • High (³8%): 45% of global population • lifetime risk of infection >60% • early childhood infections common • Intermediate (2%-7%): 43% of global population • lifetime risk of infection 20%-60% • infections occur in all age groups • Low (<2%): 12% of global population • lifetime risk of infection <20% • most infections occur in adult risk groups

    36. Geographic Distribution of Chronic HBV Infection HBsAg Prevalence ³8% - High 2-7% - Intermediate <2% - Low

    37. Concentration of Hepatitis B Virus in Various Body Fluids Low/Not High Moderate Detectable blood semen urine serum vaginal fluid feces wound exudates saliva sweat tears breastmilk

    38. Hepatitis B Virus Modes of Transmission • Sexual • Parenteral • Perinatal

    39. Risk Factors for Acute Hepatitis B United States, 1992-1993 Heterosexual* (41%) Injecting Drug Use (15%) Homosexual Activity (9%) Household Contact (2%) Health Care Employment (1%) Unknown (31%) Other (1%) * Includes sexual contact with acute cases, carriers, and multiple partners. Source: CDC Sentinel Counties Study of Viral Hepatitis

    40. Elimination of Hepatitis B Virus Transmission United States Objectives • Prevent chronic HBV Infection • Prevent chronic liver disease • Prevent primary hepatocellular carcinoma • Prevent acute symptomatic HBV infection

    41. Elimination of Hepatitis B Virus Transmission United States Strategy • Prevent perinatal HBV transmission • Routine vaccination of all infants • Vaccination of children in high-risk groups • Vaccination of adolescents • all unvaccinated children at 11-12 years of age • “high-risk” adolescents at all ages • Vaccination of adults in high-risk groups

    42. Estimated Incidence of Acute Hepatitis B United States, 1978-1995 HBsAg screening of pregnant women recommended 80 Infant immunization recommended Vaccine licensed 70 60 OSHA Rule enacted 50 Cases per 100,000 Population Adolescent immunization recommended 40 30 20 * Decline among homosexual men & HCWs Decline among injecting drug users 10 0 78 79 81 82 83 84 85 87 88 89 90 91 92 93 94 95 80 86 Year * Provisional date

    43. Hepatitis C Prepared by Hepatitis Branch Centers for Disease Control and Prevention 9/25/00

    44. Features of Hepatitis C Virus Infection Incubation periodAverage 6-7 weeks Range 2-26 weeks Acute illness (jaundice)Mild (<20%) Case fatality rate Low Chronic infection75%-85% Chronic hepatitis70% (most asx) Cirrhosis10%-20% Mortality from CLD 1%-5%

    45. Chronic Hepatitis C Factors Promoting Progression or Severity • Increased alcohol intake • Age > 40 years at time of infection • HIV co-infection • ?Other • Male gender • Other co-infections (e.g., HBV)

    46. Serologic Pattern of Acute HCV Infection with Recovery anti-HCV Symptoms +/- HCV RNA Titer ALT Normal 6 1 2 3 4 0 1 2 3 4 5 Years Months Time after Exposure

    47. Serologic Pattern of Acute HCV Infection with Progression to Chronic Infection anti-HCV Symptoms +/- HCV RNA Titer ALT Normal 6 1 2 3 4 0 1 2 3 4 5 Years Months Time after Exposure

    48. Hepatitis C Virus Infection, United States New infections (cases)/year 1985-89 242,000 (42,000) 1998 40,000 (6,500) Deaths from acute liver failure Rare Persons ever infected (1.8%) 3.9 million (3.1-4.8)* Persons with chronic infection 2.7 million (2.4-3.0)* Of chronic liver disease - HCV-related 40% - 60% Deaths from chronic disease/year 8,000-10,000 .

    49. Estimated Incidence of Acute HCV InfectionUnited States, 1960-1999 Decline in injection drug users Decline in transfusion recipients Source: Hepatology 2000;31:777-82; Hepatology 1997;26:62S-65S

    50. Prevalence of HCV Infection United States, 1988-1994 Anti-HCV Est. Infections Percent of Group Positive millions (95% CI)Infections