The Success of a Universal Hepatitis B Immunization Program as Part of Thailand's EPI after 22 Years' Implementation

Abstract

Hepatitis B vaccination for newborns was introduced in two provinces in 1988 as part of Thailand's Expanded Program on Immunization (EPI), and extended to the whole country in 1992. Our previous studies showed that children and adolescents who were born after the implementation of this program had a carrier rate of less than 1%, compared with 5-6% before implementation. In 2014 we performed hepatitis B serosurveys among 5964 subjects in the different geographic regions of the country to evaluate the long-term immunogenicity and impact of universal hepatitis B vaccination in newborns as part of the 22-year EPI program, by assessing HBsAg, anti-HBc and anti-HBs seropositivity status. The number of HB virus (HBV) carriers, both children and young adults, who were born after universal HB vaccination was markedly reduced. The carrier rates among the age groups 6 months to 5 years, 5-10, 11-20, 21-30, 31-40, 41-50 and >50 years were respectively 0.1, 0.29, 0.69, 3.12, 3.78, 4.67 and 5.99%. The seropositivity rate for HBsAg in the post-EPI group was 0.6%, whereas in the pre-EPI group it was as high as 4.5% (p<0.001). HBV infection by means of detectable anti-HBc had also drastically declined in the population born after the HB vaccine was integrated into the EPI program. We estimated that the total number of HBV carriers amounted to 2.22 million, or 3.48% of the total population, most of whom are adults. The HB vaccine is the first vaccine shown to be effective in preventing the occurrence of chronic liver disease and hepatocellular carcinoma. Universal vaccination campaign will contribute to the eventual eradication of HBV-associated disease.

Fig 1. The implementation of universal HB immunization in 1988–1992.

The Expanded Program on Immunization (EPI) began in two provinces, Chiang Mai and Chon Buri, in 1988, increased to 12 provinces in 1990, and covered the entire country by 1992.

Fig 2. Map of Thailand showing the seven provinces in this study.

Uttaradit and Phitsanulok represent the northern provinces; Lop Buri and Ayutthaya represent the central provinces; Trang and Narathiwat represent the southern provinces; and Khon Kaen represents a northeastern province (all denoted in orange).

Fig 3. The prevalence of HBV assessed by seropositivity levels of HBsAg and anti-HBc and the seroprotective level of anti-HBs.

Individuals were divided into seven age groups (<5, 5–10, 11–20, 21–30, 31–40, 41–50 and 51–60 years plus). The proportions of individuals positive for HBsAg (A), anti-HBs (B), and anti-HBc (C) are shown on the y-axis. The age at which EPI began is denoted by a vertical line. The ‘before EPI’ group was defined as individuals > 22–24 years of age (depending on the province). The ‘after EPI’ group was defined as individuals < 22–24 years of age.

Fig 4. The prevalence of HBsAg, anti-HBs, and anti-HBc among populations residing in four parts of Thailand.

The seven age groups were <5, 5–10, 11–20, 21–30, 31–40, 41–50 and 51–60 years plus (x-axis). The y-axis represents the percentage of the population with positive HBsAg (A), seroprotective anti-HBs (B) and positive anti-HBc (C).

Fig 5. The prevalence of anti-HBs and geometric mean titers (GMTs) in the Thai population.

The x-axis represents the seven age groups and the sample size in each age group. Scale on the left represents the percentage of the population with positive anti-HBs. Scale on the right represents the GMTs in each age group, with the means indicated as black squares. Antibody measurements were negative (white), 1–10 mIU/ml (blue), >10 100 mIU/ml (yellow), >100–1000 mIU/ml (dark blue) and > 1000 mIU/ml (red). GMTs were calculated from anti-HBs > 1 mIU/ml.

Fig 6. The percentage of (A) HBsAg seropositivity rate, (B) anti-HBs seroprotectivity rate and (C) anti-HBc seropositivity rate in the Thai population in 2004 and 2014.

The red line represents the data in 2014, with the means indicated as red dots, and the black line represents the 2004 data, with means indicated as black dots.

Fig 7. Estimation of the numbers of HBV carriers in the Thai population.

The x-axis represents the seven age groups. Scale on the left represents Thai population. Scale on the right represents the percentage of HBV carriers, with the means indicated by black dots.

Fig 8. The percentage of hepatitis B vaccine coverage after the vaccine was integrated into the EPI program.