Childhood immune responses to hepatitis B vaccine in Uganda.

Abstract

Introduction: Hepatitis B virus (HBV) infection is still a major global public health problem with approximately 296 million people infected. Sub-Saharan Africa is disproportionately over-burdened by HBV infection, with Uganda’s national prevalence at 10%. The Ministry of Health integrated childhood hepatitis B vaccination into the Uganda National Extended Program on Immunizations (UNEPI) in 2002 to reduce high morbidity and mortality rates. Childhood HBV immunization remains fundamental to elimination of HBV but the levels of African/Ugandan paediatric non-response and the underlying reasons largely remain unknown. This doctoral study sought to determine the extent and persistence of immuno-protection accorded by the vaccine in Uganda. Methods: A cross-sectional study design was utilized to conduct four sub studies. For the first sub study, a systematic review was conducted to synthesize data on African pediatric HBV vaccine responses, by including 19 eligible articles out of the 197 initially downloaded and published from 1999 to 2021 from African Journals Online (AJOL), EMBASE, Scopus, and, PubMed. The second and third sub studies qualitatively and quantitatively determined the serological status of vaccine and HBV exposure among childhood recipients of the hepatitis B vaccine who were under 5 and 15-17 years of age and enrolled on the UNEPI after the vaccine’s inception in 2002. The fourth sub study analyzed archived plasma samples to determine HBV and vaccine serological status among adolescent children living with HIV. For sub study two, three, and four, we assessed participants’ exposure to infection using a 5-panel qualitative hepatitis B Combo RDT methodology. Subsequently, immune responses to the hepatitis B vaccine were assessed in these participants’ serum or plasma using the quantitative electrochemiluminescence immuno assay (ECLIA). Results: Our systematic review revealed significantly higher proportion of HBV vaccine seroprotection (69.07%) among African children under 15 years of age than children 15 to 17 years (32.368%), 95 % CI = [34.2454% to 39.0847%] (p < 0.0001) . Findings from sub studies 2 and 3 showed that qualitative seroprevalence of hepatitis B surface antibody (anti-HBs) was 33.1%, 18.4%, and 5.9% in the under-5, among the 15–17-year-old study groups, and in adolescents living with HIV, respectively. However, quantitative anti-HBs analysis revealed that post vaccination, 74.3% of children under 5 years retained protective anti-HBs levels compared to only 14.6% among adolescents and 16.3% in adolescents living with HIV. The overall prevalence of HBsAg was 1.52%, with higher rates in adolescents (2.78%) than in children under 5 years (0.8%) and 2.0% among adolescents living with HIV. Conclusions: While infant HBV vaccination under UNEPI, like in most African extended programmes on Immunization (EPIs), provides commendable immune protection in children under 5 years, seroprotection wanes significantly by adolescence, increasing infection risks, especially in children 15-17 years of age and adolescents living with HIV. The apparent breakthrough HBV infections further suggest that the development of targeted adolescent strategies and guidelines addressing waning immunity will be essential to achieve the 2030 HBV elimination goals in Uganda and similar African settings.