George Papaevangelou

Epidemiology of hepatitis A in Mediterranean countries

Infection with hepatitis A virus (HAV) is still endemic in some Mediterranean areas. In most Northern Mediterranean countries, the incidence of acute icteric hepatitis in adults is increasing. This is due to the shifting of HAV infection to adulthood as a result of the decline of its overall prevalence due to improvements in socioeconomic, sanitary and hygienic conditions. The majority of adults remain susceptible and develop overt disease when infected, since the severity of disease is highly associated with age. Epidemics are now rare, but are more extensive when they do occur. They may sometimes be caused by accidental contamination of the water supply, but are usually due to contamination of food by diseased food-handlers or result from contaminated frozen foods. Outbreaks still may occur in day-care centres and in schools. Thus travelling to endemic areas is becoming the main source of HAV infection. Intrafamilial person-to-person spread also is an important source of infection. Transmission from children to parents and other adults may occur due to lack of immunity in the adult population. Selective immunization would further reduce the incidence of the disease. However, only inclusion of the vaccine in the routine programme of childhood immunization would guarantee the disappearance of hepatitis A.

Decline of hepatitis B infection in Greece.

Hepatitis B has long been a serious public health problem in Greece. In recent years, a decline in hepatitis B infection is observed ascribable to many factors such as demographic and socioeconomic changes, medical precautions, use of disposable medical equipments, screening of blood donors and vaccination. We studied the prevalence of HBV infection in a sample of 1050 Greek male Navy recruits. 343 subjects (32.6%) had previously been vaccinated and were anti-HBs positive. We observed that during the last decade, the prevalence of immunes declined to 1.33% and the prevalence of any HBV marker declined to 2.28%. The HBsAg carrier rate declined from 3.9% in 1973 to 0.9% in 1986. Since then, it is stable at 0.95% because perinatal and vertical transmissions are still responsible for the majority of HBV chronic infections. Universal prenatal screening and infant immunization will contribute to a further decline of HBV infection.

Evaluation of a combined tetravalent diphtheria, tetanus, whole-cell pertussis and hepatitis B candidate vaccine administered to healthy infants according to a three-dose vaccination schedule

A vaccine combining hepatitis B with diphtheria, tetanus and whole-cell Bordetella pertussis (DTPwHBV) would facilitate the attainment of universal vaccination of infants against hepatitis B. A candidate vaccine was administered to 42 infants beginning at 7-15 weeks of age. Antibodies were measured from pre- and postvaccination blood samples. After three doses, at least 94.9% of the infants were protected against hepatitis B, diphtheria and tetanus. Responses to B. pertussis were considered adequate. No serious adverse events were reported. These results indicate that this candidate vaccine is safe and immunogenic when administered to infants according to a three-dose schedule, with doses 2 months apart.

Hepatitis B immunization programme: lessons learnt in Greece

Historically, Greece has had the highest burden of hepatitis B virus (HBV) infection in the European Union (EU). Heterosexual contact is the primary means of HBV transmission in Greece, accounting for approximately 30% of acute cases in adult males and 50% of acute cases in women of reproductive age [Kattamis C, Papevangelou G. Workshop Group: Greece. Vaccine 1995;13:S97-S98.]. In 1982, Greece implemented a hepatitis B prevention programme aimed at high-risk groups; unfortunately, this approach had little impact on disease incidence or prevalence. At the recommendation of the WHO and the World Health Assembly and after sustained lobbying by several scientific and medical associations in Greece, the Greek government decided to implement a national prevention programme for hepatitis B. The programme, in effect from early 1998, includes the screening of pregnant women, universal infant and adolescent immunization and immunization of high-risk groups.

Current combined vaccines with hepatitis B

Hepatitis B (HB) vaccine has been included in the national immunization programmes of more than 90 countries world-wide. Its combination with DTP (diphtheria-tetanus-pertussis) and other childhood vaccines will lower administration costs, simplify vaccine administration and improve the logistics of vaccine delivery. It is believed that the combined vaccines will increase acceptance and vaccine coverage. The immunogenicity and reactogenicity of the various components should not differ when given separately or together. The combined vaccines DTP + HB, DT + HB, HA + HB, HB + Hib have already been developed and used in several countries and DTP + HB + IPV and DTP + HB + IPV + Hib combined vaccines are currently under development. Further studies are necessary to devise appropriate schedules adjusted to the epidemiological situations of each geographic region.

Hepatitis A vaccine: persistence of antibodies 5 years after the first vaccination.

The recent development of safe and effective inactivated hepatitis A vaccines provides the opportunity to control hepatitis A. However, effective control will depend upon the duration of protection provided by the vaccine. Evaluation of persistence of antibodies over time is essential for the determination of vaccination schedules and strategies. For this purpose blood samples were obtained from 140 volunteers, 5 years after the administration of three 720 ELISA units (EU) doses of an inactivated hepatitis A vaccine according to a 0, 1 and 6 month schedule. All serum samples were tested for anti-hepatitis A virus (HAV) antibodies using a sensitive ELISA inhibition assay. All subjects, except one, had anti-HAV titres > or = 20 mIU ml-1. The geometric mean titre (GMT) was 1258 mIU ml-1. All individual titres were at least 10 times higher than the minimum protective level. According to the rate of antibody level decrease over time, the predicted duration of antibodies is estimated to be at least 20 years.

Hepatitis B Maternal-Fetal Transmission in Southern Europe

Screening of pregnant women for hepatitis B surface antigen especially in countries with a high carrier rate as in Southern Europe is absolutely necessary for the control and elimination of the disease. In most Southern European countries screening of pregnant women is highly recommended. In Greece the carrier rate in pregnant women varies between 2.8 and 3.0%. However, only 63.1% of mothers at delivery had been screened before admission to the maternity hospital. To avoid legal problems arising from obligatory screening, educational campaigns, lectures, pamphlets and further measures to increase screening of pregnant women and administering hepatitis B immunoglobulin and vaccine should be taken.

Evaluation of the immunogenicity of a recombinant vaccine against hepatitis B containing S and pre-S2 sequences using two different schedules

The immunogenicities of hepatitis B virus vaccines containing S and pre-S2 regions were compared using two different schedules of immunization (A: 0-1-2-12 months and B: 0-1-6 months). Two hundred males and females aged 17-22 years were vaccinated with 20 micrograms per dose. The follow-up period was extended up to 13 months. One month after the booster dose anti-HBs were detected in 98.9% of those vaccinated with schedule A and 100% of those vaccinated with schedule B. Geometric mean titres (GMT) of anti-HBs were significantly higher with schedule A than schedule B, reaching GMT of 16269.7 mIU ml-1 and 4372.4 mIU ml-1, respectively, one month after the booster dose. Seroconversion rates for the anti-pre-S2 antibodies one month after the booster dose were 89.4% for schedule A and 76.6% for schedule B. GMT were 157.8 mIU ml-1 and 67.5 mIU ml-1, respectively. We conclude that both vaccines elicit high titres of anti-HBs and anti-pre-S2 antibodies. Immunity lasts longer in schedule A than in schedule B.

Perspectives on Viral Hepatitis Elimination in Europe

Viral hepatitis has long been a serious public health problem in Europe. Extensive epidemics occurred during wars and mass population movements. Recent improvements in standard of living and hygiene have contributed significantly to the decline in disease prevalence. Moreover, scientific progress in the diagnosis and study of the pathogenesis of viral hepatitis has defined the epidemiological characteristics of the various types of hepatitis and led to specific measures to combat the disease. The use of disposable syringes, needles, and other medical equipment, and the universal screening of blood donors greatly contributed to the elimination of iatrogenic transmission of parenterically transmitted hepatitis viruses. Finally, the discovery and extended used of the already licensed new vaccines as well as those under development will eliminate the bulk of the disease and eradicate certain types of viral hepatitis in the near future in Europe.