Hepatitis A booster vaccination: is there a need?

Hepatitis A is one of the most common vaccine-preventable infectious diseases in the world. Effective vaccines against hepatitis A have been available since 1992, and they provide long-term immunity against the infection. However, there is no worldwide consensus on how long protection will last or whether there will be a need for hepatitis A virus (HAV) booster vaccinations in the future. In most countries, booster-vaccination policy is guided by manufacturers' recommendations, national authorities, or both. In June, 2002, a panel of international experts met to review the long-term immunogenicity and protection conferred by HAV vaccine in different population groups. Data have shown that after a full primary vaccination course, protective antibody amounts persist beyond 10 years in healthy individuals, and underlying immune memory provides protection far beyond the duration of anti-HAV antibodies. The group concluded that there is no evidence to lend support to HAV booster vaccination after a full primary vaccination course in a healthy individual. However, further investigations are needed before deciding if boosters can be omitted in special patient-groups.

[New and re-emergent epidemics in the changing surrounding world]. / Nya och nygamla epidemier i en föränderlig omvärld.

In discussion of the emergence of 'new' diseases or the re-emergence of old ones, much attention has been focused on the appearance of hitherto unknown agents versus the transfer of known agents to new populations. The appearance of a new pathogenic microorganism is often assumed to be the result of a change in its genetic properties. Although this may occasionally be the case, in fact most emergent pathogens have already existed in nature. Some occurring in isolated human populations, others well-established in animal species for centuries. Microbial traffic between animals and man is of special interest. Such cross-species transfer of infectious agents is often the result of changes in human behaviour, or in such human activities as deforestation, dam-building and migration.

Studies on a Hib-tetanus toxoid conjugate vaccine: effects of co-administered tetanus toxoid vaccine, of administration route and of combined administration with an inactivated polio vaccine.

A freeze-dried tetanus toxoid (T) conjugated Haemophilus influenzae type b (Hib) vaccine, was reconstituted in either diphtheria toxoid (D), DT or a combined DT and inactivated polio vaccine (IPV), and administered in an open randomized trial either intramuscularly (i.m. ) or subcutaneously (s.c.) to 287 Swedish infants at three, five and 12 months of age. When not included in the mixture, IPV was administered s.c. at a separate site. The geometric mean concentrations of Hib antibodies after primary and booster vaccinations were 1.0 and 11.6 microg/ml, respectively, with no differences related to co-administration of the carrier protein T. Antibodies against T were induced by the T conjugated Hib vaccine (Hib-T) alone in 69/95 infants aged six months, and in 87/93 children aged 13 months, although infants receiving both Hib-T and T had significantly higher concentrations. Antibody responses to Hib, D, T or polio were not negatively influenced by administration route or by mixing with IPV, except that the mixed vaccine DT-IPV induced lower anti-polio GM titers after primary vaccination than did separate IPV. More local reactions were induced by the s.c. than by the i.m. route (P-values from 0.001 to 0.01). Slight increases in rates of local reactions and febrile events (>/=38 degrees C) occurred by order of dose. The low Hib antibody concentrations after the first two doses in this and other Swedish studies are unlikely to be of clinical relevance. The tetanus antibody response from T as a carrier protein alone was not sufficient for basic tetanus immunization, but should be considered in future use of additional T conjugated vaccines.

New target groups for vaccination against hepatitis A: homosexual men, injecting drug users and patients with chronic hepatitis.

In countries where the incidence of hepatitis A is low outbreaks of hepatitis A regularly occur among injecting drug users (IDUs) and homosexual men. Obviously these groups are important reservoirs of hepatitis A virus (HAV) and vaccination within these groups should be encouraged. In elderly patients, as well as in patients with chronic liver disease, hepatitis A infection may have a worse prognosis than in young and healthy patients. Also for that reason, patients with chronic liver disease, especially those with chronic hepatitis B and C, are target groups for vaccination against hepatitis A.

Safety and immunogenicity of hepatitis A vaccine in patients with chronic liver disease.

Acute hepatitis A superimposed on chronic liver disease (CLD) has been associated with severe or fulminant hepatitis. An open, multicenter study was performed to compare the safety and immunogenicity of an inactivated hepatitis A vaccine in patients with CLD with that in healthy subjects. A secondary objective was to compare the safety of the hepatitis A vaccine with that of a commercial hepatitis B vaccine in subjects with chronic hepatitis C. A total of 475 subjects over the age of 18 years were enrolled into 1 of 5 groups according to history, serological data, and previous diagnosis. Patients in groups 1 (healthy adults), 2 (chronic hepatitis B), 3 (chronic hepatitis C), and 5 (other CLD not caused by viral hepatitis) were vaccinated with two doses of inactivated hepatitis A vaccine, 6 months apart. Patients in group 4 (chronic hepatitis C) received 3 doses of a recombinant hepatitis B vaccine, according to a 0-, 1-, and 6-month schedule. Local injection-site symptoms were the most common reactions reported following vaccination in all groups (35.5% of all doses), with the hepatitis B vaccine eliciting fewer injection-site symptoms than the hepatitis A vaccine (19.8% compared with 37.5%). Although a higher percentage of healthy subjects (93%) seroconverted after a single dose of the hepatitis A vaccine than did subjects with chronic hepatitis C (73.7%) or CLD of nonviral etiologies (83.1%), more than 94% of all vaccinees were seropositive for anti-HAV after the complete vaccination course. At each time point, a lower geometric mean concentration of anti-HAV was observed for each group of CLD patients compared with the healthy control subjects. In conclusion, hepatitis A vaccine was well tolerated and induced a satisfactory immune response in patients with chronic hepatitis B, chronic hepatitis C, and miscellaneous CLD.

Why the Scandinavian countries have not implemented universal vaccination against hepatitis B.

Within the 50 member states of the WHO European region, HBsAg carriage rates vary from a high of approximately 20% to a low of 0.05%. The Scandinavian countries have the lowest carriage rates in the region (0.05%). The situation in Sweden is representative of the situation throughout Scandinavia: although a substantial number of immigrants to Sweden are HBsAg-positive, acute cases of hepatitis B continue to be seen mainly in drug addicts and their contacts and to a certain extent, in male homosexuals with multiple partners. Public health officials and governments in Scandinavia are unwilling to introduce universal vaccination of infants because hepatitis B infection is viewed as a limited public health problem that does not justify the expense and other efforts of universal immunization.

Report from Working Group 3 (the Czech Republic, Denmark, Finland, Norway, The Netherlands, Slovakia, Sweden and the UK).

The Czech Republic, Denmark, Finland, Norway, the Netherlands, Slovakia, Sweden and the UK all have very low HBsAg carrier rates; in the Scandinavian countries, for instance, carrier rates are on the order of 0.05%. Most countries in this group are unconvinced that the carrier rates and the burden of disease caused by new hepatitis infections warrant the expense of universal childhood immunization. In Scandinavia and the UK hepatitis B prevention programmes are based on immunization of high-risk groups. In Scandinavia (excepting Denmark), the UK and the Netherlands, pregnant women are screened and newborns of carrier mothers vaccinated. Only the Czech Republic and Slovakia--both of which now employ high-risk group strategies of hepatitis B prevention--have expressed interest in implementing programmes of universal hepatitis B vaccination of infants and/or adolescents.

Hepatitis C: natural history of a unique infection.

In 1988 investigators defined the agent causing most cases of non-A, non-B hepatitis and named this agent hepatitis C virus (HCV). Assays for antibody to HCV and more specific diagnostic tests (immunoblot and polymerase chain reactions) were subsequently developed. Exposure to HCV seems to result in chronic infection in a majority of cases, with progressive chronic liver disease sometimes leading to hepatocellular carcinoma. This virus is spread mainly by parenteral routes; intravenous drug users are at high risk. Sexual and intrafamilial spread has also been documented but seems to occur to a limited extent. Perinatal transmission, which is prominent in infection with hepatitis B virus, does not play an important role in the spread of HCV. Antiviral therapy with interferon alpha is usually tried in chronic hepatitis C but permanently normalizes liver function in only one-fourth of patients. The failure to demonstrate protective immunity after single or multiple episodes of infection raises doubts about the existence of neutralizing antibodies and concerns about the potential for the development of a vaccine against HCV.

New approaches to hepatitis A and B vaccines.

Plasma-derived vaccines and yeast-derived recombinant vaccines against hepatitis B virus (HBV) infection have gained an acceptable record of efficacy. However, non- or hyporesponsiveness to immunization does not only occur in cases of obesity, renal failure or immune suppression, but also in healthy individuals. There is therefore a rationale for developing more immunogenic vaccines against HBV, especially for those populations who are potential non- or hyporesponders. Currently used recombinant hepatitis B vaccines consist of antigen particles assembled with the product of 226 amino acids encoded in the S gene. Since proteins encoded in the pre-S gene are also incorporated in the HBV envelope, pre-S gene products should, at least in theory, be useful in improving protection with hepatitis B vaccines. Inactivated hepatitis A vaccines are more potent than currently used hepatitis B vaccines. Two injections of a standard dose of HAVRIX (SB) by the intramuscular route, or even a single injection using a higher dose (HAVRIX 1440), will achieve protective levels of antibodies. Therefore, increased potency is not essential with inactivated hepatitis A vaccines. New hepatitis A vaccines are likely to be recombinant or attenuated live types. Another aspect of the improvement of existing hepatitis A and B vaccines is unification into a combined form.