Integration of hepatitis B vaccination into national immunisation programmesBMJ 1997; 314 doi: https://doi.org/10.1136/bmj.314.7086.1033 (Published 05 April 1997) Cite this as: BMJ 1997;314:1033
- Pierre Van Damme, researchera,
- Mark Kane, medical officerb,
- André Meheuson behalf of the Viral Hepatitis Prevention Board, professora
- a Centre for the Evaluation of Vaccination, Epidemiology and Community Medicine, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium
- b Global Programme for Vaccines and Immunisation, World Health Organisation, 1211 Geneva 27, Switzerland
- Correspondence to: Dr Van Damme
- Accepted 10 September 1996
Hepatitis B is a major public health problem even though safe and effective vaccines have been available for over 10 years. Because hepatitis B infection is largely asymptomatic with long term complications occurring after many years it has not received the attention it deserves. Strategies to immunise those at high risk have failed to control the disease. Delegates to the World Health Assembly of the World Health Organisation recommended in May 1992 that all countries should integrate hepatitis B vaccination into their national immunisation programmes by 1997. Some western European countries remain unconvinced that the burden of disease warrants the expense of universal vaccination. However, epidemiological data and economic evaluation show that universal hepatitis B vaccination is cost effective in countries with low endemicity and that it will control hepatitis B, reinforcing the necessity for action.
Size of the problem
More than one third of the world's population are estimated to have been infected with hepatitis B virus. Most have recovered, but there are around 350 million chronic carriers of the hepatitis B virus, about 5% of the world's population.1 About a quarter of these carriers will develop serious liver disease, including chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma. The World Health Organisation estimates that hepatitis B infection results in more than one million deaths every year worldwide.1 2 3
Based on the prevalence of carriers of hepatitis B surface antigen in the general population, countries are classified as having high (≥8%), intermediate (2-7%), or low endemicity (<2%). In Europe the level of endemicity generally increases from north to south and from west to east, but factors such as changes in family size, high risk lifestyles, and population migration from areas of high to low endemicity are also affecting the distribution of the virus.
In most European countries notification of acute hepatitis B cases is mandatory. However, wide differences exist between case definitions and in the completeness and methods of reporting, making it difficult to draw meaningful conclusions from comparisons between countries. In addition, the number of cases notified each year is far below the true overall incidence of infection.
After correcting for underreporting and for the fact that at least half of hepatitis B virus infections are asymptomatic, the Regional Office for Europe of the WHO estimates that a million people are infected in Europe every year. Of these, about 90 000 will become chronically infected carriers and about 22 000 will die from cirrhosis and liver cancer.4 Unexpectedly high prevalences of hepatitis B carriage have been found in many parts of central and eastern Europe and the newly independent states of the former Soviet Union. In the Central Asian republics of the former Soviet Union and in some countries of central and eastern Europe (such as Albania, Bulgaria, Moldova, Romania), hepatitis B is a serious threat to community health, with an estimated annual incidence of 520 infections/100 000. These countries have intermediate or high endemicity.4 The remaining countries of central and eastern Europe have an estimated annual incidence of 130 infections/100 000. Although the need for universal hepatitis B vaccination is unquestioned in areas of intermediate and high endemicity, so far, only Albania, Bulgaria, Moldova, Poland, Romania, and Slovenia have been able to implement vaccination programmes. Most of the countries of the former Soviet Union lack the financial resources to obtain these vaccines, and donors, in general, have been unwilling financially to support integration of hepatitis B vaccines into national immunisation programmes.
Although western Europe, north America, and Australia have a low endemicity of hepatitis B virus, the incidence of new infections and the burden of acute and chronic disease place hepatitis B among the most important communicable diseases. For instance, in the United States mortality from hepatitis B was five times that from Haemophilus influenzae type B and 10 times that from measles before routine vaccination of children was introduced (unpublished data, Centers for Disease Control, 1993).
High risk strategies
Although safe and effective hepatitis B vaccines have been available for over 10 years, universal vaccination is still being postponed in many countries. One reason is the weakness of our social commitment to preventive medicine and vaccines.5 Important also is the lack of medical and public awareness: the public does not perceive hepatitis B as a threat to the population at large, and governments, expected to respond to public demand, have not considered hepatitis B prevention as a priority and have opted for selective prevention strategies. Although the incidence of hepatitis B infection has decreased in many countries as a consequence of behavioural changes secondary to the AIDS epidemic, experience has shown that targeting hepatitis B vaccine at high risk groups and screening pregnant women do not work. Such strategies, which have been used in countries with low endemicity since 1982, have failed to control hepatitis B for various reasons1 6: most high risk groups are difficult to access, there is a lack of perceived risk among those at risk, and over 30% of those with acute hepatitis B infection do not have identifiable risk factors. In some countries with low endemicity universal antenatal screening for hepatitis B is not well implemented, and even when used selective antenatal screening failed to identify about half of the pregnant women whose neonates were at risk.7 8
Except in a few countries the high risk strategy has resulted mainly in the immunisation of healthcare workers and some categories of patients–for example, those receiving haemodialysis, transplants, and multiple blood transfusions or with hepatitis C infection. About 85% of vaccine has gone to the healthcare workers, who account for only 5 to 10% of reported cases of hepatitis B infection in most European countries and North America.1 While healthcare workers should certainly be immunised, this high risk strategy will not control hepatitis B on a population basis.
Need for universal immunisation
The failure of the high risk immunisation strategy and a better knowledge of the burden of disease have emphasised the necessity for action to control the risk of acquiring hepatitis B in the community. In 1991 the global advisory group of the Expanded Programme on Immunisation recommended integration of hepatitis B vaccine into all national immunisation programmes. The deadline for countries with a prevalence of carriers of 8% or more was 1995 and for other countries was 1997.2 3 This recommendation was endorsed in May 1992 by the World Health Assembly, the governing body of the WHO. In 1994, the World Health Assembly added a disease reduction target, calling for a 80% decrease in the incidence of new hepatitis B virus carriers in children by 2001.
By early 1996 more than 80 countries included hepatitis B vaccine as a routine part of their infant or adolescent immunisation programmes. These countries represent roughly 40% of the world's 145 million newborns annually but almost 60% of the world's 350 million carriers. Of these 80 countries, 53 report hepatitis B vaccine coverage to the WHO: 40% of these countries report 80% or greater coverage with three doses of hepatitis B vaccine in infants. Many countries using adolescent immunisation have not yet established effective immunisation monitoring programmes.
Among countries with low endemicity the United States, New Zealand, Canada, France, Germany, Italy, Luxemburg, Portugal, and Spain have implemented universal vaccination programmes. The Australian National Health and Medical Research Council has recently recommended infant and adolescent immunisation. Belgium, Greece, the Netherlands, Switzerland, Turkey, and other European countries are seriously studying the issues or are making budgetary provisions for introduction of the vaccination programme.
Safety and effectiveness
Data from clinical trials as well as from universal immunisation programmes show that hepatitis B vaccines are well tolerated. Several hundred million doses of hepatitis B vaccine have been given worldwide, and no serious complications have been causally linked to vaccination.9 10 Effectiveness of the hepatitis B vaccines has been shown in several community trials. The carrier rate has been reduced from over 8% to under 2% in immunised cohorts of children in Gambia, China, Singapore, Hong Kong, Taiwan, Alaska, Thailand, Indonesia, South Korea, and American Samoa. Since the introduction of routine hepatitis B vaccination in the Alaska native population in 1983, the incidence of acute hepatitis B has fallen by over 98%, and no new carriers have been detected among those vaccinated.11 Similarly, 10 years after implementation of a mass vaccination programme in Taiwan the annual incidence of hepatocellular carcinoma in children (10-14 years) has fallen.12
In western Europe universal immunisation programmes in Spain and Italy have proved highly successful. In Italy, population surveys conducted in 1994-5 show a vaccine coverage rate of over 90% both in children and adolescents; notification data show a 50% reduction of acute hepatitis B in subjects aged 15-24 years in 1994 compared with 1988.13 14
Some decision makers in northern Europe are not convinced that the burden of disease of hepatitis B justifies the expense of universal vaccination. However, cost effectiveness studies performed in countries with low endemicity (Belgium, Canada, United Kingdom, United States) consistently find that universal vaccination is economically attractive.15 16 17 18 Health policy makers should look carefully at these studies. Cost effectiveness ratios varied from $1000 to $20 000 (£625-12 500) per discounted life year gained depending on the country's epidemiological and organisational characteristics and assumptions made about cost of vaccine and coverage. In general, these calculations compare favourably with prevention and vaccination strategies for other diseases that are already implemented and well accepted. Benefits of immunisation were increased if the indirect costs of loss of productivity among those affected were taken into account. These economic evaluations indicate that economic arguments cannot be used to delay the implementation of universal hepatitis B vaccination in countries with low endemicity.
Emerging data on the long term effectiveness of hepatitis B vaccines, knowledge that infants and adolescents can be reached through already established vaccination delivery systems, and studies showing that these interventions are cost effective, indicate that hepatitis B virus can be controlled and eliminated by universal immunisation. The choice of whether to immunise infants or adolescents depends on each country's epidemiology and organisation of the vaccine delivery systems.
In future, combination vaccines containing hepatitis B will be used. Such vaccines will mean fewer injections; save on syringes, storage, transportation, record keeping, and training; and improve acceptance, integration into existing vaccination programmes, and harmonisation of vaccination schedules. However, countries should not wait for the arrival of combined vaccines before implementing universal immunisation. In Europe much work remains to be done to implement interventions that will bring us closer to the WHO goal and to control hepatitis B in the community. Only a united effort by all those involved in preventive health care can ensure effective implementation of these important preventive measures.