Prevention of Hepatitis B: the Foundation of Viral Hepatitis Prevention Harold S. Margolis, M.D. Division of Viral Hepatitis National Center for Infectious Diseases Centers for Disease Control and Prevention Atlanta, GA

Reasons to Combine Viral Hepatitis and HIV/AIDS Prevention Major public health problems Routes of transmission overlap Effective prevention tools immunization, blood screening, universal precautions, risk reduction, treatment Well established programs for HIV/AIDS Lack of integrated prevention activities leads to transmission of both diseases, especially viral hepatitis Hepatitis C: the tipping point for a new direction in prevention

Estimated Number of Persons with Chronic Bloodborne Virus Infections 1998 Region Population (millions) HIV HCV HBV Africa 749 22.7 22.5 59.3 Asia 3,585 7.3 107.5 286.8 Latin America 504 1.7 15.1 10.3 Europe 729 0.8 21.8 10.9 Oceania 30 0.0 0.9 2.4 North America 305 9.1 1.9 Total 5,902 33.4 176.9 371.6 Chronic infections

Routes of Transmission and Opportunities for Prevention of Infection with Hepatitis Viruses and HIV Overlap Substantially

Risk Factors for Transmission of Hepatitis Viruses and HIV Proportion of Infections (%) Risk Factor Rare 30 5-7 (past) 40 15 14 HBV Past 7- 20 10 <<1 20 1 60 HCV 9 Past 2 <<1 10 47 31 HIV Transfusion Unknown Occupational Heterosexual partners MSM Injection drug use These infections are transmitted by injection drug use, and sex Relative importance differs somewhat for each agent, however, the prevention messages are the same for all three

Prevention and Control of Viral Hepatitis: its becoming more than HBV infection HAV, HBV and HCV infection are endemic in most parts of the world, including the independent states of the former Soviet Union. First priority = prevention of HBV infection in infants and young children = infant hepatitis B immunization Routine disease surveillance will identify hepatitis B and hepatitis C in other age groups 1.    Although hepatitis C virus appears to be endemic in most areas of the world, temporal and geographic differences have been observed in the epidemiology of hepatitis C that are related to differences in the frequency and extent to which various risk factors contribute to the transmission of HCV. The two risk factors most frequently cited as being responsible for transmission of HCV infection are blood transfusion from unscreened donors and injecting drug use. However, the potential roles of other medical and dental procedures, cultural practices, and high-risk behaviors have not been appreciated.

Components of a Hepatitis B Immunization Program Infant Catch-up for older children – ages defined by local epidemiology Health care workers Other high-risk adults – groups defined by local epidemiology Assessment of effectiveness of HepB immunization Vaccination coverage (age-specific) Population-based serologic assessment Acute disease surveillance Surveillance for Acute Viral Hepatitis All age groups Serologic conformation Risk factor data - immunization status, source of infection 1.    Although hepatitis C virus appears to be endemic in most areas of the world, temporal and geographic differences have been observed in the epidemiology of hepatitis C that are related to differences in the frequency and extent to which various risk factors contribute to the transmission of HCV. The two risk factors most frequently cited as being responsible for transmission of HCV infection are blood transfusion from unscreened donors and injecting drug use. However, the potential roles of other medical and dental procedures, cultural practices, and high-risk behaviors have not been appreciated.

A Model Hepatitis B Prevention Program Immunization infant catch-up for older children health care workers other high-risk adults Prevent transfusion-transmitted infection - safe blood and blood products screening of blood donors for HBsAg good manufacturing practices for blood products pooled products include virus inactivation Safe injection practices in all settings Infection control practices to prevent transmission of bloodborne infections Surveillance to assess prevention effectiveness 1.    Although hepatitis C virus appears to be endemic in most areas of the world, temporal and geographic differences have been observed in the epidemiology of hepatitis C that are related to differences in the frequency and extent to which various risk factors contribute to the transmission of HCV. The two risk factors most frequently cited as being responsible for transmission of HCV infection are blood transfusion from unscreened donors and injecting drug use. However, the potential roles of other medical and dental procedures, cultural practices, and high-risk behaviors have not been appreciated.

Injections among Unvaccinated Children < 5 years of age with Acute Hepatitis, Romania 1997-1998 Reported Cases HBV HAV Cases Controls OR 95%CI Received an injection 16 41 5.1 2.3-11 No injection 23 300 Ref Population attributable risk among unvaccinated = 32%

Prevalence of HCV Infection in Blood Donors < 0.1% - Very Low >5% - High 1.1-5% - Intermediate 0.2-1% - Low Unknown Anit-HCV Prevalence * *Anti-HCV defined by EIA and supplemental testing

Proportion of HCV Infections Attributable to Unsafe Injections Case-Control Studies Population Country Year Age Attributable % Taiwan (Ho) 1993 Children 84%* (Chen) 1990-94 Adults 20%* (Sun) 1990 Adults 57% Pakistan (Luby) 1994-95 All 51%* Egypt (El Sakka) 1996-97 All 88%* * Calculated from data provided by authors Source: SIGN, WHO

Health-Care Procedures and HCV Infection Low/Moderate Endemic Countries Surgery Dental Country HCV Pos HCV Neg HCV Pos HCV Neg Case-Control USA 10% 12% 24% 24% Italy 17%* 2% 22%* 11% Cross-Sectional Italy 56%* 36% 91%* 80% 77% 57% 90% 90% Taiwan 13% 3% 24% 28% Pakistan No data 33% 39% Japan 32%* 10% No data * P<.05, independent of other risk factors

Unsafe Injections and HCV Infection Moderate Endemic Countries History Reused Needles/Syringes Country HCV Pos HCV Neg OR (95% CI) Italy 63% 31% 3.8 (2.7, 5.3) 89% 53% 7.0 (4.4, 11.2) 76% 72% 1.2 (0.6, 2.5) Taiwan 26% 8% 4.2 (1.2, 14.5) Pakistan (>5/yr) 36% 6% 8.2 (1.9, 41.4)

Geographic Patterns of Age-Specific Prevalence of HCV Infection 10 20 30 40 50 0-9 10-19 20-29 30-39 40-49 50+ Age Group (Years) Percent Anti-HCV Positive Egypt Japan, Italy U.S., Australia

Burden of Disease Attributable to Unsafe Injections, Developing and Transitional Economy Countries, Preliminary Data HCV HBV HIV Total number of infections 4.8 m 64.7 m 5.5 m Infections attributable to unsafe injection 2.1 m 23.0 m 0.1 m Attributable fraction 44% 36% 2% Source: Armstrong, Hauri, Hutin

Posttransfusion Hepatitis in Developing Countries Inappropriate use of blood and blood products – single unit transfusions common Lack of organized transfusion services Most transfused units not tested for HBV or HCV Related donors often used – perception that less likely to be infected Paid donors continue to be used in many countries

Posttransfusion Hepatitis C All volunteer donors HBsAg Donor Screening for HIV Risk Factors Anti-HIV ALT/Anti-HBc Anti-HCV Improved HCV Tests Good afternoon- Review CDC’s progress in implementation of prgrams to prevent hepatitis C Integration into CDC’s existing public health programs Adapted from HJ Alter , et al . Clin Chem 1997

Injecting Drug Use: HBV and HCV Infection Highly efficient mode of transmission Rapidly acquired after initiation Four times more common than HIV Prevalence 50-90% after 5 years Predominant risk factor in low prevalence countries Emerging risk factor in medium prevalence countries –acute hepatitis B and hepatitis C in adults are often the best indicator of injection drug use problem

Duration of Injecting (months) Risk of Bloodborne Virus Infections Injection Drug Users Baltimore 1983–1988 20 40 60 80 100 HCV HBV Seroprevalence (%) HIV 6 12 18 24 30 36 42 48 54 60 66 72 Duration of Injecting (months) Garfein RS. Am J Public Health. 1996;86:655.

Injecting Drug Use and HCV Infection High/Moderate Endemic Countries Minor role in the distant past Highest incidence of hepatitis C now seen in young adults in some countries (e.g., Italy, Japan) sentinel event for emergence of injecting drug use History of injecting drug use becoming more common 50% of persons with acute hepatitis C (Italy, Russia) 40% of HCV-positive persons <40 yrs old vs. 0% >40 (Italy) 2/3 of HCV-positive commercial blood donors (Egypt)

Relative Importance of Risk Factors for Hepatitis C and Prevention Strategies by HCV Endemicity High/Moderate Endemicity Transfusion Other Nosocomial Sexual Other Injection Drug Use Low Endemicity Safe blood supply Safe injections Infection control Risk reduction services Testing and counseling

Relative Importance of Risk Factors for Hepatitis B and Prevention Strategies by Endemicity High/Moderate Endemicity Nosocomial Other Perinatal/Horizonal Other Injection Drugs Sex Low Endemicity Infant Immunization Safe blood supply Safe injections Infection control Infant, adolescent, adult immunization Risk reduction services