Hepatitis B vaccine

• Public Health strategies
• WHO perspective
• Special issues
• Administration summary
• References
• Statistics on Hepatitis B coverage and disease incidence
• Other useful links

Public health strategies

Hepatitis B is a viral infection of the liver. More than two thousand million people alive today have been infected with the hepatitis B virus. Approximately 350 million are chronically infected and are at high risk of serious illness and death from cirrhosis of the liver and primary liver cancer, diseases that kill 500 000 to 750 000 persons a year. Hepatitis B is preventable with a safe and effective vaccine — the first vaccine against cancer.

The prevalence of chronic hepatitis B virus (HBV) infection is high (more than 8%) in certain areas of the world. These include all of sub-Saharan Africa, South-East Asia, including China, Indonesia, the Democratic People's Republic of Korea, and the Philippines; the Eastern Mediterranean except Israel; South and Western Pacific islands; the interior Amazon Basin; and certain parts of the Caribbean, i.e. the Dominican Republic and Haiti. The disease is moderately prevalent (2%–7%) in South Central and South-West Asia, Israel, Japan, Eastern and Southern Europe, the Russian Federation, and most of Central and South America. In Australia, New Zealand, Northern and Western Europe, and North America,, the prevalence of chronic hepatitis B viral infection is low (under 2% of the general population).

If the vaccine is administered before infection, it prevents the development of the disease and the carrier state in almost all individuals. It has been given to more than 500 million persons and has proved one of the safest, most immunogenic and effective vaccines. On a population basis, it is most effective when used routinely as part of the infant immunization schedule, although it can be used in persons of any age.

Dramatic decreases in the cost of the vaccine in developing countries, from US$ 20 to $0.25–0.50 per paediatric dose, have allowed public health officials to consider the mass use of this vaccine in infants. Additionally, an increasing number of countries have recognized the disease burden imposed by chronic HBV infection in terms of chronic liver disease, cirrhosis and liver cancer. These have been important factors in promoting the integration of hepatitis B vaccine into national childhood immunization schedules.

Universal infant immunization is now recognized as the proper strategy for every country for the long-term control of chronic HBV infection and its sequelae (cirrhosis and liver cancer). The vaccine first became available in the United States in 1982 when the initial strategy was to give it as pre-exposure vaccination to populations at high risk for HBV infection (e.g. health care workers, men who have sex with men, and heterosexual persons with multiple partners). When the vaccine became widely available, a similar strategy was adopted by other industrialized countries. By the mid-1980s, several countries with very high prevalence of chronic HBV infection had begun the routine immunization of infants at birth. In 1992, WHO recommended that hepatitis B vaccine be integrated into national immunization programme of all countries with a rate of chronic HBV infection of 8% or higher by 1995, and into the programme of all countries by 1997. More than 135 countries have now done so.

WHO perspective

Hepatitis B vaccine should be included in routine childhood immunization schedules for all children in all countries. Some industrialized countries administer the vaccine to adolescents as their primary immunization strategy.

The priorities for hepatitis B immunization strategies in order of importance are:

• routine infant vaccination;
• prevention of perinatal HBV transmission (from mother to baby);
• catch-up vaccination for older age groups.

Routine infant vaccination

The routine vaccination of all infants as an integral part of national immunization schedules should be the highest priority in all countries. In countries of high disease endemicity hepatitis B surface antigen (HBsAg ) prevalence (8% or more), routine infant hepatitis B vaccination can rapidly reduce transmission because most chronic infections are acquired as a result of spread either from mother to baby or from child to child in the first year of life. In countries of intermediate hepatitis B viral endemicity (HBsAg prevalence 2%–7%) and low endemicity (HBsAg prevalence below 2%), routine infant hepatitis B vaccination is also the highest priority. This is because a high proportion of chronic infections are acquired during childhood in these countries, and most infections acquired during childhood occur among children born to mothers who are NOT infected with hepatitis B virus. These infections would not be prevented by perinatal hepatitis B prevention services that screen pregnant women for HBsAg and provide post-exposure immunization for infants of HBsAg-positive mothers.

Hepatitis B vaccine schedules are very flexible. There are various options for adding the vaccine to established national immunization schedules without requiring additional visits for vaccination (table 1).

Options for adding hepatitis B vaccine to childhood immunization schedules

* Only given in countries of high disease endemicity

(m) = monovalent vaccine (m/c) = monovalent or combination vaccine (c) = combination vaccine

Programmatically, it is usually easiest if the three doses of hepatitis B vaccine are given at the same time as the three doses of DTP (table 6, option I). This schedule prevents infections acquired during early childhood, which account for most of the disease burden related to hepatitis B virus in countries of high disease endemicity, and also prevents infections acquired later in life. However, this schedule does not prevent perinatal hepatitis B virus infections because it does not include a dose of hepatitis B vaccine at birth.

Other schedule options can be used to prevent perinatal hepatitis B virus infections: a three-dose schedule of monovalent hepatitis B vaccine, the first dose given at birth and the first and third doses given at the same time as the first and third doses of DTP vaccine (option 2); or a four-dose schedule in which a birth dose of monovalent hepatitis B vaccine is followed by three doses of a combination vaccine (e.g. DTP-HepB) (option 3).

• The three-dose schedule (option 2) is less expensive but is more complicated to administer because infants receive different vaccines at the second EPI visit than at the first and third visits. In addition, it may be difficult to achieve a high level of completion of the three-dose vaccine series with this schedule in countries where a high percentage of children are not born in hospitals.
• The four-dose schedule (option 3) is easier to administer programmatically but is more costly.

Prevention of perinatal hepatitis B virus transmission

In order to prevent hepatitis B virus transmission from mother to baby the first dose of hepatitis B vaccine needs to be given as soon as possible after birth, preferably within 24 hours. In countries where deliveries take place predominantly in health facilities the most feasible strategy for preventing transmission from mother to baby is to give a dose of hepatitis B vaccine to all infants at birth. An alternative strategy is to screen all pregnant women for HBsAg and provide immunization, beginning at birth, to infants of infected mothers. However, extensive resources are required for screening pregnant women and tracking infants of infected mothers. Moreover, few countries have implemented services that have identified all the expected infants of infected mothers and tracked these infants so as to assure completion of the hepatitis B vaccine series.

The priority for the incorporation of strategies aimed at the prevention of perinatal transmission of hepatitis B virus in a particular country should take into account the relative contribution of such transmission to the overall hepatitis B disease burden and the feasibility of delivering the first dose of hepatitis B vaccine at birth. In general it is most feasible to deliver hepatitis B vaccine at birth to infants who are born in health facilities. In addition,
the availability of monovalent hepatitis B vaccine in prefilled single-dose injection devices (e.g. UnijectÔ ) can facilitate the administration of hepatitis B vaccine by birth attendants to infants delivered at home.

When considering whether a birth dose should be given the following principles should be taken into account.

• All countries

Achieving a high level of completion of the vaccine series among all infants should be the highest priority and has the greatest overall impact on the prevalence of chronic hepatitis B virus infections in children, regardless of whether it is feasible to administer a birth dose.

• Countries where a high proportion of chronic HBV infections are acquired perinatally (e.g. in South-East Asia)

A birth dose should be given to infants who are delivered in hospitals when hepatitis B vaccine is introduced. Efforts should also be made to give hepatitis B vaccine as soon as possible after birth to infants delivered at home.

• Countries where a lower proportion of chronic infections is acquired perinatally (e.g. in Africa)

The administration of a birth dose may be considered after evaluating the relative contribution of perinatal hepatitis B virus infections to the overall disease burden, and the feasibility and cost-effectiveness of providing such a dose.

Catch-up vaccination for older age groups

When hepatitis B vaccine is incorporated into routine childhood vaccination schedules, over several years the child population will gradually become protected against HBV infection, and the prevalence of chronic HBV infection will decline. The need for catch-up vaccination for older age groups such as adolescents and adults is determined by the baseline epidemiology of HBV infection in the country, the priority given to rapidly reducing the incidence of the disease and considerations of cost-effectiveness. In all countries, health-care workers who are exposed to blood in their work are likely to be at high risk for HBV infection and should be considered for immunization.

In countries of high endemicity (HBsAg prevalence 8% or more) the routine vaccination of infants rapidly reduces the transmission of HBV. In this circumstance, catch-up vaccination of older children is not usually warranted. Catch-up vaccination for older age groups has relatively little impact, since most adults have already been infected.

In countries of intermediate endemicity (HBsAg prevalence 2%–7%) and low endemicity (HBsAg prevalence under 2%) there may be a substantial disease burden attributable to chronic infections acquired by older children, adolescents and adults. Catch-up strategies targeted on these older age groups, in addition to routine infant vaccination, may be considered. Possible target groups for catch-up vaccination include cohorts such as adolescents and persons with risk factors for acquiring hepatitis B viral infection.

Booster doses: These are not recommended. Studies have shown that infants, children and adults who have responded to a three-dose hepatitis B immunization series are protected from hepatitis B for at least 15 years even if they lose detectable antibodies over time. Long-term protection relies on the immunological memory, which allows a protective anamnestic antibody response after exposure to HBV.

Public concern: Although concerns have been expressed over the past 20 years that certain chronic illnesses might be caused by hepatitis B vaccine, no evidence exists that any of these diseases are caused by the vaccine. For example, in the mid-1990s, concern was expressed that the vaccine might cause multiple sclerosis. However, studies do not support this, and a report in 2002 by the United States Institute of Medicine found no evidence of a causal relationship between hepatitis B vaccination in adults and multiple sclerosis.

Administration summary

Key references

Andre FE, Zuckerman AJ. Review: protective efficacy of hepatitis B vaccine in neonates. Journal of Medical Virology, 1994, 44:144–51.

Centers for Disease Control and Prevention. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination: recommendations of the Immunization Practices Advisory Committee (ACIP). Morbidity and Mortality Weekly Report, 1991, 40(No. RR–13):1–25.

Centers for Disease Control and Prevention. Achievements in Public Health: Hepatitis B vaccination, United States, 1982-2002. Morbidity and Mortality Weekly Report, 2002, 51(25): 549–552.

Chang MH, Cen CJ, Lai MS, et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. New England Journal of Medicine, 1997, 336:1855–1859.

European Consensus Group on Hepatitis B Immunity. Are booster immunisations needed for lifelong hepatitis B immunity? Lancet, 2000, 355:561–565.

Harpaz R, McMahon BJ, Margolis HS, et al. Elimination of chronic hepatitis B virus infections: results of the Alaska immunization program. Journal of Infectious Diseases, 2000, 181:413–418.

Hepatitis B immunization. Introducing hepatitis B into national immunization services.
(Fact sheet.) Geneva, 2001 (unpublished document WHO/V&B/01.28; available from Vaccines and Biologicals, World Health Organization, 1211 Geneva 27, Switzerland and on the Internet at www.who.int/vaccines-documents/DocsPDF01/www598.pdf).

Institute of Medicine Immunization Safety Review Committee. In: Straton K, Almario D, McCormack MC, eds. Hepatitis B vaccine and demyelinating disorders, 2002. Washington DC: National Academy Press, 2002.

Other relevant sites and links:

Information bank; Useful facts, figures and safety of commonly used vaccines

V&B documents available on the internet

National Centre for Infectious Diseases; Home page for Viral Hepatitis

WHO Fact Sheet on Hepatitis B

Viral Hepatitis Prevention Board; Home page

International Travel and Health; Vaccination Requirements and Health Advice

Updated February 2003

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