By the time of the 1998 survey 1041 young people (833 aged 0-14 years, 208 aged
15 years) had been vaccinated in the two villages. We excluded from the study 29 infants who were below 1 year of age and 23 children who had received two or fewer doses of vaccine, leaving 989 children. Of these 989, 856 gave a blood sample, 64 refused to take part, 33 had died, and 36 could not be traced; coverage ranged from 94% for children aged 1-4 years to 81% for those between 15 and 19 years.
Effect of vaccination on pattern of infection
The figure shows that in 1984 at the start of vaccination Manduar had a much higher prevalence of hepatitis B virus infection and HBsAg carriage compared with Keneba. Between 1984 and 1998 vaccination dramatically reduced the prevalence of hepatitis B virus infection in children from 48% (302/620) to 11% (68/624) in Keneba and from 80% (246/309) to 15% (34/223) in Manduar. The corresponding changes in HBsAg carriage rates were from 13% (83/622) to 1% (6/628) in Keneba and from 35% (108/309) to 2% (4/227) in Manduar.
Vaccine efficacy by village and age
Overall, crude vaccine efficacy against HBsAg carriage was 94% (95% confidence interval 89% to 97%), which did not vary significantly between villages or by age group (table ). Overall crude vaccine efficacy against infection was 80% (76% to 84%), which did not vary between villages but differed according to age group, being significantly lower among those aged
15 years compared with any of the other younger age categories (P<0.001). After we adjusted for age and village, the overall vaccine efficacy against carriage was 94% (89% to 97%) and against infection was 82% (78% to 85%).
Table 1 Vaccine efficacy in 1998 against chronic carriage of hepatitis B virus and breakthrough infection overall by village and by age group
Duration of response and breakthrough infections in children immunised in 1984
Table shows the data obtained from groups 1, 2, and 3 at the various surveys. These participants had a median age in 1998 of 16.2 years (range 14.2-21.7 years) and had been followed up for a median of 13.8 (13.5-14.1) years. In each of the groups, which had significantly different peak antibody responses in 1985 (P<0.0001), antibody decayed in a similar and regular exponential manner with time. The proportion of uninfected participants with undetectable antibody concentrations (<10 mIU/ml) differed between the groups (P=0.001) and increased with time (P<0.0001).
Table 2 Concentrations of antibody to hepatitis B surface antigen (anti-HbsAg) and number infected over time among vaccinated children in groups 1-3
The proportion of breakthrough infections and the cumulative proportion of breakthrough infections (consisting of current infections and past infections that were no longer detectable) also increased with time (P<0.0001 in both cases), but neither of these proportions differed significantly between the groups. By 1998, 64 of the 171 (37.4%) vaccinated participants had been infected, and of the 111 uninfected participants, 40 (36%) had undetectable concentrations of antibody.
Vaccine efficacy against infection was 49.2% (27.8% to 64.3%), 36.2% (4.7% to 57.3%), and 92.3% (57.2% to 100%) for groups 1, 2, and 3, respectively (P<0.01 for comparison between group 1 or 2 and 3). In 1998 one of 54 (2%), 4 of 57 (7%), and none of 64 participants in groups 1, 2, and 3 were chronic carriers of HBsAg. Two of the chronic carriers were infected within a year of vaccination; the three others were infected five or more years later. Vaccine efficacy against chronic carriage was 91.0% (36.8% to 98.7%), 65.8% (11.3% to 86.8%), and 100% for groups 1, 2, and 3, respectively.
Breakthrough infections and chronic carriage according to peak antibody responses
Table shows that the number of breakthrough infections was related to vaccination group (P=0.01) and to the peak antibody concentration (P=0.001). Those with an undetectable (equivalent to <10 mIU/ml) response had six times the chance of infection compared with those with high responses (>999 mIU/ml). More importantly, participants whose peak antibody response was <10 mIU/ml were 75 times more likely to become chronic carriers than those with responses
10 mIU/ml (P<0.0001). Seven out of the 10 chronic carriers, all of whom had a peak antibody response of less than 10 mIU/ml, were infected before the age of 5 years.
Table 3 Hepatitis B virus infection and chronic carriage in 1998 in relation to peak antibody concentration. Figures are numbers of breakthrough infections out of total number of children with antibody response
Logistic regression analyses of breakthrough infections and chronic carriage
Table shows the independent factors associated with breakthrough infection. Time since vaccination and peak antibody concentrations were strongly associated; sex and village had a significant but lesser effect. Dose (three or four) was not significant; neither was route of administration.
Table 4 Independent factors associated with core antibody breakthrough infection
The only factor associated with chronic carriage of hepatitis B virus was a peak response of <10 mIU/ml (8/39 (20.5%) versus 2/731 (0.27%) children with a higher response (odds ratio 95, 95% confidence interval 19 to 466)).