A single dose, combined vaccine against typhoid fever and hepatitis A: consistency, immunogenicity and reactogenicity.

BACKGROUND: Vaccines against hepatitis A and typhoid fever are well established and have an excellent safety and immunogenicity profile. Yet these diseases, which share the same geographic distribution, remain an important cause of morbidity in travelers to endemic countries. Combined vaccination provides dual protection and improves compliance and coverage for travelers. METHODS: This multicenter study evaluated the consistency of three lots of combined hepatitis A and typhoid fever vaccine. A total of 462 healthy subjects, aged 15-50 years, were enrolled and randomly allocated to 3 groups. The single dose of vaccine contains 25 microg typhoid Vi polysaccharide and at least 1,440 ELISA units of inactivated hepatitis A in a 1 mL dose. RESULTS: Bioequivalence of all production lots was shown in terms of safety and immunogenicity. Pain at injection site was the most frequent reported local symptom, and headache was the most frequent reported general symptom. As early as 14 days after immunization >95% of the subjects were positive for anti-Vi antibodies and >86% were positive for anti-HAV antibodies. The GMTs and seropositivity rates were maintained during the 6 month follow-up. CONCLUSION: The first combined vaccine against typhoid fever and hepatitis A was safe and elicited a very good immune response, with the majority of subjects seropositive at 1 month for both antigens. This combined vaccine offered more convenience and rapid seroconversion to travelers.

Mathematical models for assessment of long-term persistence of antibodies after vaccination with two inactivated hepatitis A vaccines.

Very few studies with inactivated hepatitis A vaccines were designed for long-term follow-up of antibody persistence. Based on the serological data from these vaccine trials, mathematical models were developed to predict the decrease of anti-hepatitis A virus (anti-HAV) antibodies after vaccination. This study was designed to compare Avaxim (0-6 months) to Havrix 720 (0-1-6 months). In this paper, both groups of vaccinees are described considering the age, gender, and weight of the subjects at enrollment. For mathematical modelling, two different approaches were used: one starting the calculations from the geometric mean titres (GMTs) at each point in time, the other basing the calculations on individual anti-HAV titres. Both vaccines are very immunogenic, although Avaxim shows a higher GMT at each point in time. When these data are used in mathematical models to predict the persistence of anti-HAV antibodies, both vaccines (Avaxim and Havrix 720) show similar long-term antibody kinetics. Antibody levels > or = 20 mIU/ml are estimated to last on average for at least 10 years after completion of the full vaccination course. Ten years after the full course, approximately 53% of subjects are estimated to have antibody levels > or = 20 mIU/ml. At 15 years, these levels will be maintained by about 34% of vaccinees. Avaxim and Havrix 720 show a similar long-term profile of persistence of anti-HAV. A mathematical model based on GMTs appeared to give equivalent results to a model based on individual serological data. The GMT method is easier to apply than the individual based method. However, the advantage of the latter method is the possibility of calculating confidence limits for the predicted values and making estimates of the percentage of subjects having a certain level of antibody titres at a certain time.

The shift in prevalence of hepatitis A immunity in Flanders, Belgium.

The purpose of this study was to obtain data on the prevalence of hepatitis A in Flanders, Belgium, in order to analyse any change in the epidemiological pattern of hepatitis A virus (HAV) in the region, and to determine at which age pre-vaccination testing would be useful. To meet these goals, a sero-epidemiological survey was conducted: 4058 serum samples were collected from a random sample of the general population in 1993-94. The overall age-standardised prevalence was 51.3%. Among non-Belgians (N = 245), the age-standardised anti-HAV prevalence was 66.4%, significantly higher than the 49.6% anti-HAV prevalence found in Belgians (N = 3186). Among Belgians, seroprevalence increased with age: from 5.4% in the youngest age group (0-14 years) to over 80% in the two oldest age groups (55-64 years and > or = 65 years). Prevalence rates were as high as 31.7% in the 25-34 year old age category, and 60.8% in the 35-44 year old age category. The age-specific prevalence figures among Belgians and non-Belgians reflect two different epidemiological patterns: the epidemiological pattern of a low endemic region for Belgians and the epidemiological profile of an intermediate endemic region forn non-Belgians. The age-specific prevalence figures in Belgians were compared with the 1979 and 1989 anti-HAV prevalence figures in Belgian first-time blood donors. A clear epidemiological shift showing decreasing HAV prevalence in the youngest age groups was found. If we accept that pre-vaccination screening is useful at a 35% prevalence rate, all persons over 35 years of age should be screened before vaccination.

Prevalence of hepatitis A, B and C in the Flemish population.

Viral hepatitis is a serious health problem throughout the world. No recent prevalence data on hepatitis A, B and C were available for the population in Flanders, Belgium. For this reason, a sero-epidemiological study was undertaken in 1993-1994 in a sample of the general population. The purpose of this study was to obtain a clear picture of the prevalence of hepatitis A, B and C. Between April 1993 and February 1994, 4,058 blood samples were drawn and collected in 10 hospitals in Flanders. The study group was representative for the Flemish population. For hepatitis A a seroprevalence of 55.1% was found. In the non-Belgian residents the HAV prevalence was significantly higher than in Belgians (62% versus 52%; chi2 = 8.05; p = 0.005). For hepatitis B. 9.9% of the study group showed serological evidence of hepatitis B markers: 6.9% of the participants was positive for anti-HBs/anti-HBc, 0.7% appeared to be HBsAg positive and 3.5% was solely anti-HBs positive. The prevalence of HBV markers in Belgians was 6.9%, significantly lower compared to the 13.4% among non-Belgians (chi 2 = 14.05; p = 0.00018). 4055 serum samples were analysed for hepatitis C serology by second generation anti-HCV tests. Anti-HCV was detected in 0.87% of the serum samples. No statistically significant difference was found in HCV prevalnece between Belgians and non-Belgians. Results of this study should help policy makers in their decisions on the most appropriate hepatitis A and B vaccination strategy and on the most effective prevention strategy for hepatitis C.