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

曼氏血吸虫感染和治疗对乌干达慢性乙型肝炎病毒 (HBV) 感染病程的临床和免疫学影响

• 批准号: 10161721
• 负责人: Ponsiano Ocama
• 金额: $ 13.49万
• 依托单位: INFECTIOUS DISEASES INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-08 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10161721
• 关键词: Address; Africa; Africa South of the Sahara; Antiviral Agents; Biological Assay; Biopsy; Blood; Blood specimen; CD8B1 gene; Cessation of life; Chronic Hepatitis B; Clinical; Clinical Management; Collection; Communicable Diseases; Country; DNA; Data; Development; Diagnosis; Diagnostic Procedure; Disease; Epidemiology; Feces; Foundations; Funding; Future; Geography; Grant; HIV; Hepatitis B Prevalence; Hepatitis B Virus; Hygiene; Image; Immune; Immune response; Immunologics; Immunology; Incidence; Individual; Infection; Infrastructure; Institutes; Interferon Type II; Investigation; Liver; Liver Fibrosis; London; Malignant neoplasm of liver; Measures; Medical Research; Microscopy; Morbidity - disease rate; National Cancer Institute; Natural Killer Cells; Nature; Patients; Pattern; Persons; Praziquantel; Prevalence; Primary carcinoma of the liver cells; Process; Public Health; Research; Research Infrastructure; Research Institute; Research Personnel; Risk; Schistosoma mansoni; Schistosoma mansonii infection; Schistosomiasis; Schools; Serology; Serum; Serum Markers; Staging; Technology Transfer; Tropical Medicine; Uganda; Ultrasonography; Universities; Urine; Viral hepatitis; Virus; Virus Diseases; Work; base; career development; chronic liver disease; clinical investigation; co-infection; cohort; follow-up; improved; infection burden; insight; liver biopsy; mortality; novel; peripheral blood; response; socioeconomics; treatment response; viral DNA; virology

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.

曼氏血吸虫（Sm）和B肝炎病毒（HBV）都是撒哈拉以南非洲的地方性感染， 患病率、发病率和死亡率都很高。在乌干达，Sm和HBV的流行率估计为25%， 10%。Sm感染使免疫应答偏向Th2和调节模式， 可能在HBV感染的不同阶段导致显著的免疫相互作用。但受限 数据说明了Sm和HBV共感染的临床或免疫学影响。提出的是一种临床和 机制研究，以表征Sm感染对 慢性HBV。由精通领导病毒性肝炎高水平研究的乌干达研究人员领导， 血吸虫病流行病学和免疫学，这项研究建立在长期合作的基础上， 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。 在目的1中，我们利用新的和标准的方法描述了慢性HBV患者Sm感染的过程。 用于诊断Sm的测定，同时建立用于长期研究的个体队列。 在目标2中，我们系统地评估了HBV血清学、病毒学和疾病的临床指标（例如，纤维扫描， 超声）与吡喹酮治疗后6个月相比，然后长达3年 的后续行动。在目标3中，我们探讨了比较肝活检和外周血的免疫学研究 样本，以评估Sm和HBV相互作用可能发生的潜在机制。这些研究支持 技术转让的一种新的，高灵敏度的钐测定，以及直接支持的职业发展， 几名乌干达早期调查员拟议研究的结果将为以下方面提供新的见解： 改善Sm和HBV合并感染的临床管理和机制理解， 非洲许多地区同时发生这两种感染的地方病。