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

曼氏血吸虫和乙肝病毒都是撒哈拉以南非洲的地方性感染， 相当高的患病率、发病率和死亡率。在乌干达，Sm和乙肝的患病率估计为25%， 分别为10%。SM感染偏向Th2免疫应答和调节模式 可能会在乙肝病毒感染的不同阶段产生显著的免疫相互作用。然而，有限的 数据说明了Sm和乙肝病毒混合感染的临床或免疫学影响。建议的是一种临床和 Sm感染对血吸虫病过程影响性质和大小的机理研究 慢性乙肝病毒。由精通领导病毒性肝炎和高水平研究的乌干达调查人员领导 血吸虫病流行病学和免疫学，这项研究建立在两国之间长期合作的基础上 乌干达、美国和英国的调查人员，并利用大量的国内研究基础设施和专业知识。 在目标1中，我们用新的和标准的方法描述了慢性乙肝患者Sm感染的过程。 用于诊断Sm的检测，同时建立用于长期研究的个人队列。 在目标2中，我们系统地评估乙肝病毒血清学、病毒学和疾病的临床措施(例如，纤维扫描， 在研究开始时)与吡喹酮治疗后六个月，然后长达三年进行比较 跟进的问题。在目标3中，我们探索比较肝活检和外周血的有重点的免疫学研究。 以评估Sm和乙肝病毒相互作用可能发生的潜在机制。这些研究支持 一种新的、高灵敏度的Sm分析的技术转让以及直接支持 几名乌干达早期调查人员。拟议研究的结果将为以下方面提供新的见解 提高对Sm和乙肝病毒混合感染的临床管理和机制的认识 对于这两种感染同时发生的非洲许多地区来说。

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.