Project Abstract Hepatitis B virus (HBV) remains endemic in sub-Saharan Africa (SSA), despite an effective vaccine. While perinatal transmission from mother-to-child has been the prevailing theory for continued HBV endemicity based on studies in Asia, limited evidence from SSA suggests transmission at the household- and community-levels is a more important driver of transmission in SSA contexts. Given that scale-up of HBV vaccination will be slow and insufficient to reach the World Health Organization goal of HBV elimination by 2030, additional prevention measures are needed for HBV control, which first require a better understanding of HBV transmission in SSA. The Democratic Republic of the Congo (DRC) has a national HBV prevalence of ~3.3%, which translates to approximately 3.5 million chronic infections in a setting where advanced hepatology care is essentially inaccessible. This proposal builds upon a strong research infrastructure (~20 years) between scientists at the University of North Carolina at Chapel Hill (UNC) and in DRC’s capital city, Kinshasa, to study HBV transmission using data and samples from an ongoing household-based case-control study and from the DRC’s latest national Demographic and Health Survey. The overall goal of this proposal is to improve understanding of HBV transmission in a low-resourced, sub-Saharan Africa setting. The specific aims of this proposal are: 1) Characterize the epidemiology of HBV transmission in households in urban Kinshasa, DRC, and identify associated individual, household, and community risk factors; and 2) Investigate evidence of community-level horizontal transmission using phylogenetic analysis. Through this research proposal and a carefully constructed training plan, the trainee will achieve the following fellowship goals: 1) develop a unique and interdisciplinary research skillset that integrates epidemiology, geography, genetics, and infectious diseases; 2) engage in meaningful clinical training that will enhance the trainee’s future clinical practice and the translation of research findings to clinically relevant interventions; and 3) develop professional skills that will facilitate a successful academic career as a physician-scientist.