Clinical and immunological impact of Schistosoma mansoni infection and treatment on the course of chronic hepatitis B virus (HBV) infection in Uganda

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Schistosoma mansoni (Sm) and hepatitis B virus (HBV) are both endemic infections in sub-Saharan Africa with substantial prevalence, morbidity and mortality. In Uganda, prevalence estimates for Sm and HBV are 25% and 10%, respectively. Sm infection biases immunological responses towards Th2 and regulatory patterns which could potentially result in significant immune interactions at various stages of HBV infection. However, limited data address the clinical or immunological impact of Sm and HBV coinfection. Proposed is a clinical and mechanistic investigation to characterize the nature and magnitude of impact from Sm infection on the course of chronic HBV. Led by Ugandan investigators proficient in leading high-level research on viral hepatitis and Schistosomiases epidemiology and immunology, this study builds on long-standing collaborative work between Ugandan, US, and UK investigators and leverages substantive in-country research infrastructure and expertise. In Aim 1, we characterize the course of Sm infection in chronic HBV patients utilizing both novel and standard assays for diagnosing Sm, while concurrently establishing a cohort of individuals for longer-term investigation. In Aim 2, we systematically evaluate HBV serology, virology and clinical measures of disease (e.g., Fibroscan, ultrasound) at study entry compared to six months post praziquantel treatment, and then over up to three years of follow-up. In Aim 3, we explore focused immunological studies comparing liver biopsy to peripheral blood samples to evaluate potential mechanisms by which Sm and HBV interaction may occur. These studies support technology transfer of a novel, highly sensitive Sm assay as well as directly support the career development of several early-stage Ugandan investigators. Findings from the proposed studies will provide novel insight for improving the clinical management and mechanistic understanding of Sm and HBV coinfection, with implications for many regions of Africa with co-occurring endemics of these two infections.