Preparing for the next public debate: universal vaccination against hepatitis B

WHO have long called for universal vaccination against hepatitis B worldwide. However, in north-western Europe low incidence of the disease has fueled debate whether targeted or universal vaccination strategies are the way to go for. Careful assessment has made it clear that the extensive targeted hepatitis B vaccination programmes in the Netherlands nevertheless fail to reach a significant part of the risk groups and have not succeeded in eliminating the disease. Modelling suggests that the public health benefits obtained through targeted programmes could be augmented considerably by universal vaccination. Therefore, the Minister of Health of the Netherlands has decided to implement universal vaccination by October 2011. We illustrate the case of the Netherlands and explore lessons, which can be learnt from the vaccination programmes against HPV and influenza A/H1N1 and how to prepare for a potential public debate that might arise when implementing universal vaccination against hepatitis B.     

Hepatitis B immunisation programmes in European Union,Norway and Iceland: Where we were in 2009?

In January 2009 25 European Union (EU) Member States (MSs), Norway and Iceland, participated in a survey seeking information on national hepatitis B vaccination programmes. Details of vaccination policy, schedule, population groups targeted for vaccination, programme funding, vaccine coverage and methods of monitoring of vaccine coverage were obtained. Twenty (74%) countries reported that they have a universal hepatitis B vaccination programme, in addition to immunisation of at risk groups; seven (26%) countries recommend HBV for high risk groups only (with some inter-country variation on groups considered at high risk). Among countries without universal hepatitis B vaccination programmes, the major factor for non-introduction is low disease endemicity.     

Hepatitis B: vaccination programmes in Europe--an update

In the eight years since the Global Advisory Group of the Expanded Program on Immunisation set 1997 as the target for integrating hepatitis B (HB) vaccination into national immunisation programs world-wide, more than 116 countries have included HB vaccine as part of their routine infant or adolescent immunisation programs. Meanwhile, many countries have performed economic evaluation studies, while others have initiated sero-epidemiological studies to generate input data for burden of disease calculation. These studies have indicated that epidemiological and economic arguments cannot be used to delay the implementation of universal hepatitis B vaccination. Some countries have improved their surveillance system and included viral hepatitis in the surveillance programs. Other have put hepatitis B vaccination on the political agenda. By the year 2000, following countries of the WHO European Region (51 countries) have implemented a universal hepatitis B immunisation programme: Andorra, Albania, Austria, Belarus, Belgium, Bulgaria, Estonia, France, Germany, Greece, Italy, Israel, Kazakhstan, Kyrgyzstan, Latvia, Lithuania, Luxembourg, Malta, Moldova, Monaco, Poland, Portugal, parts of the Russian Federation, Romania, Slovakia, Slovenia, San Marino, Spain, Switzerland, Turkey and Uzbekistan. The Netherlands and some other European countries are seriously studying the issues or are making budgetary provisions for introduction of HB vaccine into their vaccination programme. Most of the European countries, which now use the vaccine routinely, have started with adolescent or infant immunisation. Belgium (1999), France (1994) and Italy (1991) have begun with both adolescent and infant HB immunisation. France continues since 1st October 1998 with the infant immunisation programme only. The rewards of effective implementation of the programmes in these countries are becoming apparent; and their success offers an exemplary model for other countries. The deadline was 1997. Globally, work still remains to be done to support and implement interventions that will bring us closer to the WHO goal and to control, eliminate and eradicate hepatitis B in the coming generations at large. If all the 145 million infants born in 1991 had been vaccinated in this way, the number of chronic carriers would have been reduced by 7.5 million, and 1.8 million deaths prevented.     

The global impact of vaccination against hepatitis B: a historical overview

Hepatitis B virus (HBV) infection is a world wide public health problem of major concern. HBV infection may lead to chronic liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Vaccination is the most effective measure to control and prevent hepatitis B and its long-term serious sequelae on global scale, both in terms of cost-effectiveness and benefit-cost ratios. According to the WHO recommendations, universal vaccination has been currently implemented in 168 countries world wide with an outstanding record of safety and efficacy. The effective implementation of such programmes of vaccination has resulted in a substantial decrease in disease burden, in the carrier rate and in hepatitis B-related morbidity and mortality. A future challenge is to overcome the social and economic hurdles which still hamper the introduction of hepatitis B vaccination on a global scale.     

Hepatitis B school-based vaccination programmes in the USA: a model for hepatitis A and B

Following the recommendation for routine vaccination against hepatitis B virus for newborns, many states have started school-based catch-up vaccination of 11- to 12-year-olds. Implementation of these programmes requires educational and promotional initiatives to increase awareness among parents, children, teachers, school nurses, school boards and administration. Experience in Framingham, Massachusetts, suggests that over 90% of targeted hepatitis B vaccine coverage can be achieved. Because hepatitis B vaccination targeted at high-risk groups in the USA was largely unsuccessful, this suggests that the initial similar targeted approach with hepatitis A vaccination will also fail. Only about 50% of hepatitis A cases have a known risk factor, and multiple high-risk areas exist throughout the USA. However, the geographical clustering of these high-risk areas and the occurrence of periodic outbreaks, suggest that school-based hepatitis A vaccination programmes may be effective in reducing the risk of infection. A voluntary programme in San Antonio achieved 43% of the targeted coverage in its first year, and a compulsory programme is due to start in Oklahoma. The effectiveness of this programme is not yet known, but future recommendations are likely to include hepatitis A vaccination as a school entry requirement in areas with high incidence of hepatitis A.     

Long-term efficacy of hepatitis B vaccine, booster policy, and impact of hepatitis B virus mutants

The long-term efficacy of hepatitis B vaccine, long-term effectiveness of hepatitis B immunisation programmes, immune memory induced by hepatitis B vaccine, current booster policies, and impact of hepatitis B virus mutants on immunisation programmes were reviewed at the Viral Hepatitis Prevention Board (VHPB) meeting in Sevilla, Spain, March 2004. The main focus was on universal vaccination programmes with data being presented from Italy, Saudi Arabia, Singapore, Spain, Taiwan, Thailand, The Gambia, and USA (Alaska).     

Markers of hepatitis B virus infection and immunity in Victoria, Australia, 1995 to 2005

Objective: Estimating the prevalence of chronic hepatitis B virus (HBV) infection in generally low-prevalence populations containing communities with a higher disease burden is difficult. This study was conducted to estimate the prevalence of serological markers of infection with, and immunity to, HBV in the Victorian population and to analyse trends in these estimates over time.
Methods: A serological survey of 3,212 samples of convenience collected in the years 1995, 2000 and 2005 was conducted using a selection procedure designed to reduce selection bias. All samples were tested for hepatitis B surface and core antibodies; all core antibody positive samples (indicating previous infection) were then tested for the presence of hepatitis B surface antigen (HBsAg).
Results: HBsAg prevalence was 1.1% (95%CI 0.8-1.6%) with significant differences observed by area of residence, age, gender and test year. Serological evidence of immunisation in infants and adolescents were lower than established estimates following the introduction of universal vaccination for these groups.
Conclusions: This study emphasises the significant and growing problem of chronic HBV infection in Victoria and suggests lower than expected population immunity deriving from universal vaccination programs.
Implications: Greater efforts are needed to formulate a comprehensive public health response to address this relatively neglected blood borne viral infection, the burden of which is very significant in some marginalised sections of our community. Increased attention to improving the universality of our immunisation programs is also needed.     

Factors influencing hepatitis B vaccine uptake in injecting drug users

BACKGROUND: Hepatitis B infection in injecting drug users is an important public health problem. Active immunization against hepatitis B is immunogenic and safe, but uptake rates in targeted vaccination programmes are low. This study was undertaken to identify factors associated with the uptake of hepatitis B vaccination in injecting drug users attending a needle exchange service. METHODS: A retrospective cross-sectional survey of case-note data of injecting drug users who had no markers of hepatitis B infection or immunity was undertaken within a drop-in needle exchange service for injecting drug users in a large urban area in England. A qualitative study using semi-structured interviews with needle exchange staff was also conducted. RESULTS: Of 207 injecting drug users, 180 (87 per cent) had been offered vaccine, 123 (59 per cent) accepted at least one dose and 55 (27 per cent) received three or more doses. Vaccine was less likely to be offered to those sharing injecting equipment or known to have hepatitis C. Needle sharing was also associated with failure to accept vaccine, as was increasing age and the length of contact with the service. CONCLUSIONS: Those who are most at risk are least likely to be offered vaccine and accept it. This calls into doubt the effectiveness of hepatitis B vaccination strategies targeted at high-risk groups and adds weight to arguments for universal vaccination.     

Prospects for vaccination against hepatitis A and B in Catalonia (Spain)

Catalonia is in an area of intermediate endemicity for hepatitis A virus (HAV) infection. An Expert Committee has recently proposed the implementation of universal hepatitis A vaccination for 12-year-olds, based on the fact that no risk factors can be identified for hepatitis A in 50% of cases, and also that selective vaccination targeted at high-risk groups has a limited potential to reduce the incidence of hepatitis A. The well-established programme of hepatitis B vaccination of pre-adolescents in Catalonian schools has high levels of vaccination coverage. This will provide a means to introduce hepatitis A vaccination in a cost-effective way in schools, by replacing the single vaccine with the combined hepatitis A and B vaccine. High-risk groups will also continue to be targeted. A pilot programme has commenced in the 1998/1999 school year and will be evaluated after 3 years. If it is successful, it will be extended indefinitely.     

Recommendations are needed for adolescent and adult pertussis immunisation: rationale and strategies for consideration.

Pertussis vaccination of infants has dramatically reduced disease, complications and deaths in infancy and early childhood. But there is still a major public health challenge--to deal with the morbidity and economic burden of illness in older children, adolescents and adults. Furthermore, it is these groups that form a major source of infection for non-immunised and partially immunised infants who are at high risk of severe complications. Adult-type acellular pertussis vaccine confers safe and effective protection against pertussis. There are several strategies to consider for immunising older individuals. Universal vaccination of all age groups would be the best available strategy for protecting individuals. It would also reduce the potential for transmitting the disease to other susceptibles, particularly infants. However, such a policy may be difficult both logistically and economically at this time. More easily achievable as a first step would be a strategy of universal adolescent booster vaccination combined with a programme targeted at adults most likely to have contact with very young babies including healthcare and childcare workers, parents and close family contacts. There is also potential for offering vaccination to adults (and their carers and close contacts) whose medical conditions or advanced age may place them at increased risk of more severe pertussis disease. Specific details of immunisation programmes must be made on a country by country basis depending on local circumstances.     

Do selective immunisation against tuberculosis and hepatitis B reach the targeted populations? A nationwide register-based study evaluating the recommendations in the Norwegian Childhood Immunisation Programme

BackgroundSelective immunisation is an alternative to universal vaccination if children at increased risk of disease can be identified. Within the Norwegian Childhood Immunisation Programme, BCG vaccine against tuberculosis and vaccine against hepatitis B virus (HBV) are offered only to children with parents from countries with high burden of the respective disease. We wanted to study whether this selective immunisation policy reaches the targeted groups.MethodsThe study population was identified through the Norwegian Central Population Registry and consisted of all children born in Norway 2007–2010 and residing in Norway until their second birthday, in total 240,484 children. Information on vaccinations from the Norwegian Immunisation Registry, and on parental country of birth from Statistics Norway, was linked to the population registry by personal identifiers. The coverage of BCG and HBV vaccine was compared with the coverage of vaccines in the universal programme.ResultsAmong the study population, 16.1% and 15.9% belonged to the target groups for BCG and HBV vaccine, respectively. Among children in the BCG target group the BCG vaccine coverage was lower than the coverage of pertussis and measles vaccine (83.6% vs. 98.6% and 92.3%, respectively). Likewise, the HBV vaccine coverage was lower than the coverage of pertussis and measles vaccine in the HBV target group (90.0% vs. 98.6% and 92.3%, respectively). The coverage of the targeted vaccines was highest among children with parents from South Asia and Sub-Saharan Africa. The coverage of vaccines in the universal programme was similar in targeted and non-targeted groups.ConclusionsChildren targeted by selective vaccination had lower coverage of the target vaccines than of vaccines in the universal programme, indicating that selective vaccination is challenging. Improved routines for identifying eligible children and delivering the target vaccines are needed. Universal vaccination of all children with these vaccines could be considered.     

Model based analysis of hepatitis B vaccination strategies in the Netherlands

We used a mathematical model for the transmission of hepatitis B infection to compare the effectiveness of different vaccination strategies in the Netherlands. Vaccination of children of immigrants from high and medium endemic countries is an effective strategy in countries with substantial immigration of carriers from high and medium endemic countries. A targeted vaccination programme for sexually highly active risk groups has a moderate additional effect if continued over a long time period. Universal vaccination has the largest effect on the incidence of new infections at the cost of having to vaccinate many more individuals than in targeted programmes. The impact on the prevalence of chronic hepatitis B infection, however, remains limited.     

The impact of immigration and vaccination in reducing the incidence of hepatitis B in Catalonia (Spain)

ABSTRACT: * Background The Hepatitis B virus (HBV) infection is a major cause of liver disease and liver cancer worldwide according to the World Health Organization. Following acute HBV infection, 1-5% of infected healthy adults and up to 90% of infected infants become chronic carriers and have an increased risk of cirrhosis and primary hepatocellular carcinoma. The aim of this study was to estimate the reduction in hepatitis B incidence due to universal vaccination programmes in Catalonia (Spain), taking population changes into account, and to construct a model to forecast the future incidence of cases that allows the best preventive strategy to be adopted. * Methods Reported acute hepatitis B incidence in Catalonia according to age, gender, vaccination coverage, percentage of immigrants and the year of report of cases was analysed. A statistical analysis was made using three models: generalized linear models (GLM) with Poisson or negative binomial distribution and a generalized additive model (GAM). * Results The higher the vaccination coverage, the lower the reported incidence of hepatitis B (p <0.01). In groups with a vaccination coverage > 70%, the reduction in incidence was 2-fold higher than in vaccinated groups with a coverage <70% (p <0.01). The increase in incidence was significantly higher in groups with a high percentage of immigrants and more than 15% (p <0.01) in immigrant males of working age (19-49 years * Conclusions The results of the adjusted models in this study confirm that the global incidence of hepatitis B has declined in Catalonia after the introduction of the universal preadolescent vaccination programme, but the incidence increased in male immigrants of working age. Given the potential severity of hepatitis B for the health of individuals and for the community, universal vaccination programmes should continue and programmes in risk groups, especially immigrants, should be strengthened.     

Cost effectiveness of hepatitis B vaccination strategies in Ireland: an economic evaluation

BACKGROUND: In accordance with World Health Organization recommendations, many European countries have introduced universal hepatitis B vaccination policies. The UK and Ireland are exceptions. In this study, we conducted an economic evaluation of a universal infant hepatitis B vaccination programme, using a six-component vaccine, compared with the current selective strategy of vaccinating high-risk infants with a monovalent hepatitis B vaccine. METHODS: A cost effectiveness analysis was conducted using a Markov model. The perspective of the analysis was the Irish Health Service Executive. Unit cost and resource utilization data were derived from expert clinical opinion, published sources, diagnosis-related group costs for hospital admissions and local cost estimates for medical fees and laboratory investigations. A full probabilistic sensitivity analysis was undertaken. Both costs and outcomes were modelled over a period of 80 years and discounted at 3.5%. RESULTS: Assuming an incidence of acute hepatitis B virus (HBV) infection in Ireland of 8.4 per 100,000 population, the incremental cost effectiveness ratio ranged from euro10,992/life years gained (LYG) to euro67 200/LYG, at the lowest and highest price estimates for the six-component vaccine, respectively. The cost effectiveness of universal versus selective hepatitis B vaccination was sensitive to the risk of acute HBV infection, the cost of the universal infant vaccination programme and the discount rate. CONCLUSION: At a cost of euro29.00 per dose of the six-component vaccine, universal infant hepatitis B vaccination is cost effective at euro37 018/LYG. This compares favourably with other preventive programmes in Ireland.     

A dynamic model for assessing universal Hepatitis A vaccination in Canada

Vaccination against Hepatitis A virus (HAV) in Canada is currently targeted toward high-risk groups. However, universal vaccination has been adopted in several other countries with a similar disease burden. Here we develop an age-structured compartmental model of HAV transmission and vaccination in Canada to assess potential universal vaccination strategies. The model predicts that universal vaccination at age 1 (respectively 4, 9, 15), with phasing out of targeted vaccination, would reduce reported incidence by 60% (respectively 52, 36, 31%) and mortality attributable to HAV by 56% (respectively 45, 26, 25%), relative to continued targeted vaccination, over 80 years.     

Hepatitis B immunisation rates among infants in ethnic groups with high prevalences of hepatitis B surface antigen carriers

Abstract: To determine hepatitis B immunisation rates in infants from ethnic groups with hepatitis B surface antigen chronic carrier prevalence over 5 per cent, a questionnaire was sent to all Maternal and Child Health Centres in Victoria, requesting information on the hepatitis B and diphtheria–tetanus–pertussis (DTP) or combined diphtheria–tetanus (CDT) immunisation status for all infants born between 1 July 1992 and 30 June 1993 and at risk of hepatitis B infection because of maternal ethnicity. We received data on 3611 of 5744 infants (62.9 per cent) in targeted ethnic groups. Of these, 12.8 per cent had not received hepatitis B vaccine, and 81.6 per cent, 76.8 per cent and 64.0 per cent had received at least one, two and three doses respectively, while 84 per cent had received at least three doses of DTP vaccine and/or CDT vaccine. Coverage with DTP or CDT was higher than for hepatitis B vaccine ( P < 0.001), and coverage was better in areas with a higher percentage of infants in high–prevalence ethnic groups ( P < 0.001). Changes in the program in Victoria in terms of timing of the first dose of vaccine plus greater attention to follow–up may lead to improved hepatitis B immunisation rates among infants in targeted ethnic groups. Adoption of universal infant hepatitis B immunisation, by increasing familiarity with hepatitis B vaccine, is likely to be the best way to increase immunisation coverage for these infants.     

The importance of imported infections in maintaining hepatitis B in The Netherlands

In The Netherlands, in May 1999 an enhanced surveillance of hepatitis B was begun to collect detailed information of patients with acute hepatitis B virus (HBV) infection. The objective was to gain insight in transmission routes and source of infection of new HBV cases. Through public health services, patients were interviewed on risk factors. It appeared that the majority (59%) acquired the infection through sexual contact; 52% of these by homosexual and 48% by heterosexual contact. In 60% of the heterosexual cases, the source of infection was a partner originating from a hepatitis B-endemic region. Sexual transmission is the most common route of transmission of acute hepatitis B in The Netherlands and introduction of infections from abroad plays a key role in the current epidemiology of HBV. As well as prevention programmes targeted at sexual high-risk groups, prevention efforts should focus more on the heterosexual transmission from HBV carriers.     

Hepatitis A and B in children and adolescents--what can we learn from Puglia (Italy) and Catalonia (Spain)?

Viral hepatitis remains a major contributor to the global disease burden. Mass immunisation strategies against hepatitis B have been adopted by more than 90 developing and industrialised countries. Countries with low hepatitis A endemicity are experiencing cyclical outbreaks and an epidemiological shift, with larger numbers of individuals at risk of infection at an older age, resulting in increased morbidity. The high cost of outbreaks in these countries has made immunisation strategies cost-effective. The development of a vaccine against hepatitis A and a combined vaccine against hepatitis A and hepatitis B offers potentially exciting opportunities for a preventative approach in areas of both low and high endemicity. Existing mass immunisation programmes against hepatitis B will facilitate the adoption of joint strategies illustrated by the examples of Puglia (Italy) and Catalonia (Spain).     

Impact of universal vaccination programmes on the epidemiology of hepatitis B: 10 years of experience in Italy

Ten years have elapsed since routine vaccination of infants and of 12-year-old adolescent was implemented in Italy. In this period, evidence has accumulated on the epidemiological impact of universal immunisation. Coverage is on average >90% and is >or=95% in many areas of the country. Incidence of acute hepatitis B, that was already declining before 1991, was further decreased by routine vaccination programmes.This is particularly evident in adolescents and young adults (cohorts involved by mandatory vaccination), while incidence shows little changes in older subjects according to data of the last years. Prevalence of hepatitis B virus (HBV) markers detected by sero-epidemiological studies on anonymous sera confirms both the very high coverage with hepatitis B vaccination and the virtual absence of chronic HBsAg carriers in cohorts involved by routine vaccination programmes. The system of passive surveillance on adverse events following hepatitis B vaccination supports the excellent safety record of hepatitis B vaccines. In a hyperendemic area of Southern Italy, where a pilot programme was firstly implemented, it was also possible to document the decline of the involvement of hepatitis B in chronic liver pathologies (from 48% in 1982 to 18% in 1997). If coverage rates are maintained at the present levels, elimination of HBV transmission in Italy may be envisaged in few decades.     

Targeted hepatitis B vaccination--a cost effective immunisation strategy for the UK?

OBJECTIVE: To compare the potential cost effectiveness of vaccination against hepatitis B virus (HBV) targeted at genitourinary clinic (GU) attendees with that of universal infant vaccination. DESIGN: A mathematical model of sexual and perinatal transmission of HBV was used to compare the effectiveness among heterosexual and homosexual populations of programmes of mass infant vaccination and targeted immunisation of genitourinary medicine (GU) clinic attendees. Each was applied to 90% of the eligible population with differing assumptions about rates of compliance and seroconversion - problems of delivery (obtaining high compliance) was considered a significant drawback of targeted vaccination. Observed relationships between GU clinic attendance and sex partner change rates for heterosexuals and for homosexuals were used to define the rates of vaccination uptake within sexual activity risk groups. SETTING: England and Wales. RESULTS: Model results showed that for heterosexuals universal infant vaccination became more effective than clinic based vaccination only approximately 40 years after the start of the programme and that the predicted cost effectiveness of GU clinic vaccination was greater at all times. For homosexuals, clinic vaccination was always more effective over the time frame considered, but by 50 years if it were carried out without prior screening it had become appreciably less cost effective than a mass infant programme. With prior screening in GU clinics this cost effectiveness deficit was only marginal. CONCLUSIONS: Targeted vaccination might have a much greater potential than is realised at present, particularly if it were possible to improve compliance of clinic attendees. A fuller comparison between mass infant and targeted vaccination must await the specific inclusion in the model of other risk groups such as intravenous drug users. An important determinant of the relative merits of the two approaches is the relationship between rates of attendance and of changing sexual partners. Further research on this is required.