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 strategies tailored to different endemicity levels: Some considerations

Hepatitis B is a serious public health problem. Worldwide three different levels of hepatitis B endemicity (high, intermediate and low) can be distinguished. Areas with different levels of endemicity require tailored vaccination strategies to fit the needs for individuals at risk and/or countries, depending on the infection risk per age group, vaccination rate, duration of protection after vaccination, cost effectiveness of vaccination strategies and ease of implementation in the national immunization schedules.This opinion paper evaluates these factors and proposes a combination of infant risk group and universal adolescent vaccination for low endemic countries thus targeting the different groups at risk. A universal infant vaccination schedule starting with a newborn vaccination within 24 h after birth is more appropriate in intermediate- and high-endemic regions.     

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.     

Hepatitis B vaccination coverage among adults aged ≥ 18 years traveling to a country of high or intermediate endemicity,United States, 2015

BackgroundPersons from the United States who travel to developing countries are at substantial risk for hepatitis B virus (HBV) infection. Hepatitis B vaccine has been recommended for adults at increased risk for infection, including travelers to high or intermediate hepatitis B endemic countries.PurposeTo assess hepatitis B vaccination coverage among adults ≥ 18 years traveling to a country of high or intermediate endemicity from the United States.MethodsData from the 2015 National Health Interview Survey (NHIS) were analyzed to determine hepatitis B vaccination coverage (≥1 dose) and series completion (≥3 doses) among persons aged ≥ 18 years who reported traveling to a country of high or intermediate hepatitis B endemicity. Multivariable logistic regression and predictive marginal analyses were conducted to identify factors independently associated with hepatitis B vaccination.ResultsIn 2015, hepatitis B vaccination coverage (≥1 dose) among adults aged ≥ 18 years who reported traveling to high or intermediate hepatitis B endemic countries was 38.6%, significantly higher compared with 25.9% among non-travelers. Series completion (≥3 doses) was 31.7% and 21.2%, respectively (P < 0.05). On multivariable analysis among all respondents, travel status was significantly associated with hepatitis B vaccination coverage and series completion. Other characteristics independently associated with vaccination (≥1 dose, and ≥ 3 doses) among travelers included age, race/ethnicity, educational level, duration of U.S. residence, number of physician contacts in the past year, status of ever being tested for HIV, and healthcare personnel status.ConclusionsAlthough travel to a country of high or intermediate hepatitis B endemicity was associated with higher likelihood of hepatitis B vaccination, hepatitis B vaccination coverage was low among adult travelers to these areas. Healthcare providers should ask their patients about travel plans and recommend and offer travel related vaccinations to their patients or refer them to alternate sites for vaccination.     

中国乙型肝炎疫苗免疫策略及新生儿以外人群接种乙型肝炎疫苗的可行性分析

中国是乙型肝炎(乙肝)病毒(Hepatitis B Virus,HBV)高感染率国家,实施国家乙肝疫苗(Hepatilis B Vac-cine,HepB)预防接种后,乙肝病毒表面抗原(HBsAg)携带率在免疫人群中显著下降,控制乙肝取得显著成就.然而,要进一步降低HBV的感染率,需不断完善国家的免疫策略,在落实新生儿HepB免疫规划的基础上,将HepB预防接种向儿童和成人高危人群扩大.     

Sero-epidemiology of mumps in western Europe

Six countries (Denmark, England and Wales, France, Germany, Italy and The Netherlands) conducted large serological surveys for mumps, in the mid-1990s, as part of the European Sero-Epidemiology Network (ESEN). The assay results were standardized and related to the schedules and coverage of the immunization programmes and the reported incidence of mumps. Low incidence of disease and few susceptibles amongst adolescents and young adults was observed in countries with high mumps vaccine coverage (e.g. The Netherlands). High disease incidence and large proportions of mumps virus antibody negative samples in adolescent and young adult age groups was noted in countries with poor vaccine coverage (e.g. Italy). The build-up of susceptibles in older children and adolescents in England and Wales, France, the former West Germany and Italy indicate the possibility of further mumps outbreaks in secondary school environments. To control mumps in western Europe, current MMR immunization programmes will need to be strengthened in a number of countries. Sero-surveillance of mumps is an important component of disease control and its usefulness will be enhanced by the development of an international mumps standard.     

Hepatitis B epidemiology in Asia, the Middle East and Africa

Asia and Africa have previously been classified as areas of high endemicity for hepatitis B virus (HBV), but in some countries highly effective vaccination programmes have shifted this pattern towards intermediate or low endemicity. Thus, China is now the only country in Asia where HBV endemicity is high. Countries with intermediate endemicity include India, Korea, the Philippines, Taiwan and Thailand, and those with low endemicity include Japan, Pakistan, Bangladesh, Singapore, Sri Lanka and Malaysia. Most countries in Africa have high HBV endemicity, with the exceptions of Tunisia and Morocco, which have intermediate endemicity. Zambia has borderline intermediate/high endemicity. In the Middle East, Bahrain, Iran, Israel and Kuwait are areas of low endemicity, Cyprus, Iraq and the United Arab Emirates have intermediate endemicity, and Egypt, Jordan, Oman, Palestine, Yemen and Saudi Arabia have high endemicity. All of these Middle East countries reach a large proportion of their population with hepatitis B vaccination, which is reducing the infection rate, particularly in Saudi Arabia. The vaccination programme in Taiwan has also greatly reduced the HBV infection rate. Future vaccination programmes must take into account the mode of transmission of HBV, the healthcare infrastructure to deliver vaccination, and the socioeconomic and political factors in each individual country, to determine the most cost-effective way of infection control.     

The transmission dynamics of hepatitis B in the UK: a mathematical model for evaluating costs and effectiveness of immunization programmes.

Complex hepatitis B (HBV) epidemiology makes it difficult to evaluate and compare effectiveness of different immunization policies. A method for doing so is presented using a mathematical model of HBV transmission dynamics which can represent universal infant and adolescent vaccination strategies and those targeted at genito-urinary (GU) clinic attenders and infants born to infectious mothers. Model structure, epidemiological underpinning, and parameterization, are described. Data from the UK National Survey of Sexual Attitudes and Lifestyles is used to define patterns of sexual activity and GU clinic attendance; data deficiencies are discussed, in particular that of UK seroprevalence of HBV markers stratified by age, sex, and risk factors. General model predictions of endemic HBV marker prevalence in homosexual and heterosexual populations seem consistent with published UK data. The simulations exhibit non-linearities in the impact of different vaccination strategies. Estimated number of carriers prevented per vaccine dose for each strategy provides a measure of costs and benefits, varying temporally over the course of a programme, and with level of vaccine coverage. Screening before vaccination markedly increases payback per dose in homosexuals but not in heterosexuals; mass infant vaccination gives the poorest effectiveness ratio and vaccination of infants after antenatal screening the best; in general, increasing vaccine coverage yields lower pay-back per dose. The model provides a useful framework for evaluating costs and benefits of immunization programmes, but for precise quantitative comparison more UK epidemiological data is urgently needed.     

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.     

Simultaneous injection of hepatitis B vaccine with BCG and killed poliovirus vaccine.

In most developing countries, hepatitis B virus is endemic and prevention has to be carried out early in life and on a mass scale. In these regions, simultaneous administration of multiple antigens is normal practice. We have therefore investigated the interaction of hepatitis B vaccine with BCG and inactivated polio vaccine. The serological antibody response to poliovirus and HBsAg as well as the cellular immune response to tuberculin post BCG immunization were assessed. The immune responses to HBsAg, BCG and polio vaccines injected simultaneously were comparable to those observed after separate administration of each vaccine. Moreover, no increase of adverse reactions was noted. Results confirmed that HB vaccine could be introduced into the WHO expanded programmes on immunization without impairing the expected protective efficacy against the targeted vaccine-preventable diseases.     

Measuring hepatitis B uptake in a new universal infant program

BACKGROUND: Vancouver-Richmond Health Board has the highest reported rate of hepatitis B in Canada, including an annual average of 25 cases in children under 12 years of age, based on reports from 1994-1997 inclusive. The current provincial adolescent grade-six hepatitis B immunization program does not protect against childhood infection. The regional health board implemented universal infant hepatitis B immunization in September 1998. METHOD: Immunization coverage data were obtained on a random sample of 191 infants born in March 1999 one year after initiation of the program. RESULTS: By eight months of age, 97.9% of children had received some vaccinations. 73.8% of infants had received three doses of hepatitis B vaccine and 12.6% had received two doses. In comparison, 89% had received three doses and 7.9% two doses of DPTP-Hib vaccine. 13.1% of infants had not received any hepatitis B vaccine. For a majority (67%) of these children, their physician's lack of awareness or lack of acceptance of the program constituted the reason for no hepatitis B vaccine uptake. Only one parent cited adverse publicity as the reason for refusing vaccination. INTERPRETATION: This survey reveals a successful first year of the program without harm to the pre-existing childhood vaccination programs. Hepatitis B vaccine uptake can be improved by increased awareness among physicians and parents.     

Prevalence of HBsAg mutants and impact of hepatitis B infant immunisation in four Pacific Island countries

The prevalence rate of hepatitis B virus (HBV) infection in Pacific Island countries is amongst the highest in the world. Hepatitis B immunisation has been incorporated into national programmes at various times, often with erratic supply and coverage, until a regionally co-ordinated programme, which commenced in 1995 ensured adequate supply. The effectiveness of these programmes was recently evaluated in four countries, Vanuatu and Fiji in Melanesia, Tonga in Polynesia and Kiribati in Micronesia. That evaluation established that the programmes had a substantial beneficial impact in preventing chronic hepatitis B infection [Vaccine 18 (2000) 3059]. Several studies of hepatitis B vaccination programmes in endemic countries have identified the potential significance of surface gene mutants as a cause for failure of immunisation. In the study outlined in this paper, we screened infected children and their mothers for the emergence and prevalence of these variants in specimens collected from the four country evaluation. Although the opportunity for the emergence of HBV vaccine escape mutants in these populations was high due to the presence of a considerable amount of the virus in the population and the selection pressure from vaccine use, there were no "a" determinant vaccine escape mutants found. This suggests that vaccine escape variants are not an important cause for failure to prevent HBV transmission in this setting. Other HBsAg variants were detected, but their functional significance remains to be determined. The failure to provide satisfactory protection during such immunisation programmes reflects the need for achieving and sustaining high vaccine coverage, improving the timeliness of doses as well as improving 'cold-chain' support, rather than the selection of vaccine-escape mutants of HBV.     

Progress in the control of hepatitis B infection in the Western Pacific Region

Hepatitis B virus infection is a serious problem globally, and particularly in the Western Pacific Region where the population suffers disproportionately from the infection and its sequelae. By 2001, every immunization programme in the Region had included hepatitis B vaccine in their schedule. However, many challenges remain if every one of the 26 million children born in the 37 countries and areas of the Region each year is to be protected against hepatitis B infection. In 2003, the Regional Committee of the World Health Organization's Western Pacific Region resolved to improve hepatitis B control by making it one of two new pillars for strengthening the Expanded Programme on Immunization. The Committee endorsed the strategies of the Regional Plan to improve hepatitis B control through immunization, reducing chronic HBV infection (chronic carriage rate) to less than 1%, and aiming for coverage of at least 80% of the birth cohort in every district with three doses of hepatitis B vaccine by 2005. To help guide this process, an assessment was made of the progress to date, and is reported in this paper. Coverage data used in this evaluation were not independently verified, and could over-estimate progress made in some countries. Whilst there has indeed been great progress in the Region, a number of national programmes still lack the ability to reach all children with immunization services. Other major issues that need to be addressed are the challenges of delivering a timely birth dose, and for certain countries, the affordability of the vaccine over the short- and long-term.     

Global progress toward universal childhood hepatitis B vaccination, 2003

In 1992, the World Health Organization (WHO) set a goal for all countries to integrate hepatitis B vaccination into their universal childhood vaccination programs by 1997. This report summarizes the global progress achieved toward vaccination of children against hepatitis B virus (HBV) infection. Although many countries have introduced hepatitis B vaccination into their national vaccination programs, efforts are needed to increase coverage with the 3-dose hepatitis B vaccination series and expand vaccination programs into countries where the vaccine has not yet been introduced.     

Crucial factors that influence cost-effectiveness of universal hepatitis B immunization in India

This study examines the parameters crucial to cost-effectiveness of universal hepatitis B immunization in India. An incremental cost-effectiveness analysis was done using a decision tree (Markov model) to follow up a hypothetical cohort of 100,000 newborns for the effects of hepatitis B acquired vertically at birth. The measure of effectiveness was disability-adjusted life-years gained. Uncertainty analysis and Scenario analysis were done using Latin hypercube sampling. Hepatitis B endemicity is the most important factor, followed by the cost of vaccine. Other factors of some influence are vaccination coverage, vaccine efficacy, HBeAg positivity, and vaccine wastage.     

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.     

Global control of hepatitis B virus: does treatment-induced antigenic change affect immunization?

Since its widespread introduction, the hepatitis B vaccine has become an essential part of infant immunization programmes globally. The vaccine has been particularly important for countries where the incidence of hepatitis B virus-related hepatocellular carcinoma is high. Effective treatment options for individuals with chronic hepatitis B infection were limited until 1998 when lamivudine, the first nucleoside analogue drug, was introduced. As a single treatment agent, however, lamivudine has a significant drawback: it induces lamivudine-resistant hepatitis B virus strains that may pose a risk to the global hepatitis B immunization programme. Mutations associated with drug treatment can cause changes to the surface antigen protein, the precise part of the virus that the hepatitis B vaccine mimics. However, the emergence of antiviral drug-associated potential vaccine escape mutants (ADAP-VEMs) in treated patients does not necessarily pose a significant, imminent threat to the global hepatitis B immunization programme. Nonetheless, there is already evidence that current treatment regimens have resulted in the selection of stable ADAP-VEMs. Treatment is currently intended to prevent the long-term complications of hepatitis B virus infection, with little consideration given to potential adverse public health impacts. To address individual and public health concerns, trials are urgently needed to find the optimal combination of existing drugs that are effective but do not induce the emergence of ADAP-VEMs. This paper examines the mechanism of antiviral drug-selected changes in the portion of the viral genome that also affects the surface antigen, and explores their potential impact on current hepatitis B immunization programmes.     

Hepatitis-B vaccine introduction into the routine immunization schedule--Andhra Pradesh experience

Hepatitis B is a viral infection of the liver and is serious global public health problem with a high risk of death from cirrhosis of the liver and liver cancer, diseases that kill about one million persons each year globally. Globally, of the 2 billion people who have been infected with the hepatitis B virus (HBV), more than 350 million have chronic (lifelong) infections. It is preventable with safe and effective vaccines that have been available since 1982. Although the vaccine will not cure chronic hepatitis, it is 95% effective in preventing chronic infections from developing, and is the first vaccine against a major human cancer. More than 160 countries have already added this vaccine to their routine immunization programmes. Available epidemiologic studies in India and AP indicate that India is in intermediate endemic status (with a prevalence of 2 to 7%) and the best way to reduce the prevalence as per the strategies outlined by WHO is to introduce Hep-B vaccine into routine immunization. AP is the first State in India to introduce Hep-B vaccine in the routine immunization in a phased manner. In-spite of the initial apprehensions and slow take up, the program is proven to be successful and Govt. of India has made budgetary provisions in the 10th plan for introduction in rest of India.     

Modelling rubella in Europe

The prevention of congenital rubella syndrome (CRS), as a complication of rubella infection during pregnancy, is the main aim of rubella vaccination programmes. However, as vaccination of infants leads to an increase in the average age at which those who were not immunized become infected, certain rubella vaccination programmes can lead to an increase in the incidence of CRS. In this paper we use a mathematical model of the transmission dynamics of rubella virus to investigate the likely impact of different vaccination policies in Europe. The model was able to capture pre- and post-vaccination patterns of infection and prevalence of serological markers under a wide variety of scenarios, suggesting that the model structure and parameter estimates were appropriate. Analytical and numerical results suggest that endemic circulation of rubella is unlikely in Finland, the United Kingdom, The Netherlands, and perhaps Denmark, provided vaccine coverage is uniform across geographical and social groups. In Italy and Germany vaccine coverage in infancy has not been sufficient to interrupt rubella transmission, and continued epidemics of CRS seem probable. It seems unlikely that the immunization programmes in these countries are doing more harm than good, but this may be partly as a result of selective immunization of schoolgirls. Indeed, in both these countries, selective vaccination of schoolgirls with inadequate vaccination histories is likely to be an important mechanism by which CRS incidence is suppressed (unlike the other countries, which have had sufficiently high infant coverage rates to withdraw this option). Reducing inequalities in the uptake of rubella vaccine may bring greater health benefits than increasing the mean level of coverage.     

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).