The World Health Assembly called for all countries with moderate or high hepatitis B virus (HBV) endemicity to institute routine immunization of all infants by 1995, and by 1997 over 80 countries had introduced HBV vaccine into their national programmes (1). Nevertheless, even though the effectiveness of immunizing infants has been demonstrated (2-5), many countries cannot afford HBV vaccine, the most expensive of the six vaccines in the Expanded Programme on Immunization (EPI). As a result, extensive reservoirs of HBV still exist, with some 95% of the 350 million carriers of the virus residing in poorer developing countries (6).
To reduce costs, countries have turned to plasma-derived HBV vaccines, rather than the more expensive recombinant vaccines. For example, the lowest tender price for recombinant vaccine in 1999 was US$ 5.50 (R 42.89) per 10-dose vial, compared to a tender price of US$ 3.72 (R 29.03) in 2000 for plasma derived vaccine. Although fears about the safety of plasma-derived vaccines still persist, it is generally accepted that they are both safe and effective (7). The efficacy of reduced doses of HBV vaccine has been investigated in an attempt to further decrease costs. Efficacy studies in young adults have shown highly satisfactory seroresponses using only half the recommended dose (8, 9), and adequate immunogenicity has been demonstrated using one-fifth of the recommended dosage in neonates (10), infants, and young children (11, 12). On the other hand, suboptimal seroresponses were observed when half the recommended dose was used to immunize neonates born to non-carrier mothers in Hong Kong (13) and to HBV-carrier mothers in China (Taiwan) (14). WHO has cautioned against using arbitrary dose reductions to save costs without approval from the national controlling authority and without first obtaining evidence that adequate immunogenicity would still be retained (15). In other studies, reducing the number of doses also resulted in unsatisfactory seroresponses (11, 16).
A low-cost plasma-derived HBV vaccine (Hepaccine B, Cheil Foods and Chemicals Company, Seoul, Republic of Korea) has been developed by inactivating the plasma-derived vaccine through flash heating--a procedure that is claimed to enhance HBV immunogenicity (17). In some adult studies this vaccine has been found to be highly immunogenic, with 94-97% seroconversion using only a 3-[micro]g dose (18, 19). However, the seroconversion rate has been reported to be as low as 52% in one study (20), while in another the seroresponse was slower with low-dose than with conventional doses of the vaccine (21). Similarly, in infants and children, both satisfactory (94% seroconversion) (22) and highly unsatisfactory seroresponses (58% seroconversion) (23) have been reported. Nevertheless, an efficacy study in a rural South African infant population immunized with Hepaccine B at the EPI scheduled ages of 6, 10 and 14 weeks demonstrated that 93% of the infants developed protective titres of antibodies to anti-hepatitis B surface (anti-HBs) markers (24), and in April 1995 the South African government introduced the Hepaccine B vaccine into the routine EPI programme (25).
To date, there has been no study of the effectiveness of this low-dose plasma-derived vaccine under field conditions, even though it could be an affordable solution for universal immunization programmes in developing countries. South Africa is a good location to carry out such a study, since HBV endemicity is high--estimates of the prevalence of hepatitis B surface antigen (HBsAg) range from 9.9% among adult migrant mineworkers from rural areas (26) to 10.1% among rural African children aged 0-6 years in the Eastern Cape Province (27). In this paper, we describe the effectiveness of the South African universal EPI-based immunization programme, which uses the Hepaccine B vaccine.
The study was a cross-sectional investigation of the prevalence of HBsAg, anti-HBs, and anti-hepatitis B core (anti-HBc) markers among 18-month-olds one year after they had been immunized for viral hepatitis B according to the EPI schedule at 6, 10, and 14 weeks of age. …