The impact of a Hepatitis B birth dose vaccine on HBV immunogenicity and incidence in children in the DRC

点击翻译按钮获取中文摘要

PROJECT SUMMARY Over the past few decades, viral hepatitis has become a leading cause of death globally, causing more deaths each year than malaria, HIV/AIDS, or tuberculosis. When considering Hepatitis B (HBV), this large burden of disease is largely driven by childhood infections, as 90% of infants infected with HBV will develop chronic hepatitis with lifelong sequelae. Childhood HBV infection occurs through vertical transmission (from mothers to children during childbirth) and through horizontal transmission (between members of the same household or community). In sub-Saharan Africa (SSA), where HBV remains endemic, children are vaccinated against HBV at 6, 10, and 14 weeks of age. This schedule does not protect against vertical transmission, and an estimated 1% of newborns (367,250 infants) in SSA continue to be infected with HBV at birth each year. Administration of the monovalent HBV vaccine at birth has been shown to have up to 95% protective efficacy against vertical transmission in the WHO Western Pacific region. However, few studies have been conducted to characterize the potential impact of providing a birth dose of HBV vaccine in sub-Saharan African settings. Our partners for this project, the Ministry of Health in the Democratic Republic of the Congo (DRC) are particularly interested in understanding whether to adopt a national HBV birth dose intervention. This translational study will provide estimates of the effectiveness and impact of a 4-dose HBV vaccine series (including a birth dose) in the DRC. The proposed research will utilize previously collected data and dried blood spots from two trials in Kinshasa Province, DRC: the Birth Dose Immunogenicity Study and the Continuous Quality Improvement Study. Using advanced epidemiological methods and mathematical modeling, this proposal aims to 1) compare the proportion of infants who achieve protective immunity to HBV at 12 months of age by vaccine dose series and mothers' HBV and HIV status and 2) model the impact of adopting a national 4-dose HBV vaccine series, including the birth dose, on the incidence of HBV in children under 5 in the DRC. The results will provide valuable estimates of the immunogenicity and potential impact of an HBV birth dose that will inform vaccine policy in the DRC and greater sub-Saharan African region. Through the completion of these research aims, the trainee will gain a unique set of skills in advanced epidemiologic methods, mathematical modeling, and vaccine intervention research. Expert mentors in vaccinology, immunology, modeling, and epidemiology will support the trainee's successful completion of the proposed research, associated training plan, and MD/PhD degree at the University of North Carolina at Chapel Hill. This F30 fellowship will aid the applicant's development as a future interdisciplinary physician-scientist practicing at the intersection of infectious disease, infant health, and interventional epidemiology.