Uganda Schistosomiasis Multidisciplinary Research Centre (U-SMRC)

乌干达血吸虫病多学科研究中心（U-SMRC）

• 批准号: 10434979
• 负责人: Alison Elliott
• 金额: $ 53.97万
• 依托单位: UGANDA VIRUS RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-09 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10434979
• 关键词: Address; Adult; Affect; Aflatoxins; Africa; Africa South of the Sahara; African; Age; Antigens; Biological; Biomphalaria; Case-Control Studies; Child; Chronic; Clinical; Collection; Communities; Complement; DNA; Data; Detection; Development; Disease; Ecosystem; Educational workshop; Enrollment; Environment; Epidemiology; Evolution; Fostering; Foundations; Frequencies; Fresh Water; Future; Genetic; Goals; Health; Helminths; Hemorrhage; Hepatitis B; High Prevalence; Human; Human Activities; Immune response; Infection; Interdisciplinary Study; International; Intervention; Intestines; Investigation; Joints; Lead; Leadership; Life; Life Cycle Stages; Life Style; Liver Fibrosis; Location; Malaria; Mentors; Modeling; Morbidity - disease rate; Nursery Schools; Nutritional; Outcome; Parasites; Pathogenesis; Persons; Pharmaceutical Preparations; Policies; Population; Population Genetics; Portal Hypertension; Praziquantel; Predisposition; Prevalence; Prevention; Prevention strategy; Research; Research Design; Research Personnel; Residual state; Risk; Risk Factors; Rivers; Sampling; Schistosoma; Schistosoma mansoni; Schistosoma mansonii infection; Schistosome Parasite; Schistosomiasis; Scientist; Seminal; Severity of illness; Site; Snails; Solid; Surveys; Translations; Tropical Medicine; Uganda; Variant; base; biological specimen archives; career; case control; co-infection; cohort; differential expression; disability-adjusted life years; doctoral student; empowered; exposed human population; genetic variant; geographic difference; immunogenic; immunoregulation; infection rate; infection risk; microbiome; mortality; neglected tropical diseases; next generation; nutrition; preventive intervention; programs; response; stool sample; transmission process; vector control

SUMMARY Schistosomiasis is a major neglected tropical disease, estimated to affect 240 million people worldwide, leading to loss of a minimum of 1.9 million disability-adjusted life years (DALYs) annually – 90% of this burden in sub- Saharan Africa. In East Africa, Uganda has a strong track-record of seminal studies and partnerships on schistosomiasis research. The Uganda Schistosomiasis Multidisciplinary Research Center (U-SMRC) will build on this solid foundation to develop a vibrant, Uganda-led, Uganda-based international schistosomiasis research network that fosters African capacity for transformative tropical medicine research. Uganda is highly endemic for Schistosoma mansoni (Sm). Intestinal schistosomiasis is universal in many villages around its Great Lakes and the River Nile. The Ministry of Health’s Vector Control Division (VCD), responsible for schistosomiasis control, has long been concerned by the high rates of severe schistosomal morbidity in the North-Western Lake Albert region (LA), compared to the Central and Eastern Lake Victoria region (LV), despite comparable transmission and programmes of praziquantel mass drug administration. In response to this concern, the U-SMRC’s core research goal is to understand the biological determinants of severe Sm- associated morbidity and to identify better strategies for its prevention and control. We hypothesise that key biological determinants of severe schistosomal morbidity occur at each stage of the parasite’s life cycle: in the human host, in the parasite, and in the snail host and its environment. To investigate this hypothesis, we will use two study designs: (i) cohorts of pre-school-age children (PSAC) in LA and LV, to explore the early evolution of immune responses that may lead to severe morbidity and (ii) an adult case control study to identify chronic exposures associated with severe disease. We will also collect parasite and snail samples from both settings, and develop a specimen archive for future studies. Our specific aims will be to Aim 1. Compare early-life immune responses to Sm exposure and infection between LA and LV and identify co-exposures that modulate Sm-specific immune responses and morbidity risk Aim 2. Establish a platform for local genetic surveillance of schistosome parasites in Uganda and determine whether there is a parasite genetic basis to differences in clinical outcomes in LA and LV Aim 3. Determine which population biological determinants of Biomphalaria spp. snails act as local epidemiological drivers of Sm, filtering its diversity within and between LA and LV ecosystems; and whether detection of environmental (e)DNA signatures from Biomphalaria and Sm can be used to better predict snail/parasite diversity at transmission sites and (re)infection risk within key demographic groups Data from each Aim will be used to develop a comprehensive, integrated model of the drivers of severe Sm- associated morbidity. This model will be further utilised to evaluate likely benefits of selected interventions, and to guide future policy on prevention and management.

概括 血吸虫病是一种主要被忽视的热带疾病，估计会影响全球2.4亿人 每年至少丧失190万残疾调整的终身年份（达利人） - 占该烧伤的90％ 撒哈拉非洲。在东非，乌干达拥有强大的第二次研究和合作伙伴关系的赛道 血吸虫病研究。乌干达血吸虫病多学科研究中心（U-SMRC）将 建立在这个坚实的基础的基础上，开发出充满活力的，乌干达，总部位于乌干达的国际血吸虫病 促进非洲变革性热带医学研究能力的研究网络。 乌干达对曼氏菌（SM）的血吸虫是高度的。在许多村庄 在它的大湖和尼罗河周围。卫生部向量控制部（VCD），负责 对于血吸虫病控制，长期以来一直关注的是严重血吸虫发病率的高率 与中央和东部维多利亚湖地区（LV）相比 Praziquantel群众药物管理的可比传播和计划。为此回应 令人担忧的是，U-SMRC的核心研究目标是了解严重SM-的生物决定者 相关的发病率并确定更好的预防和控制策略。 我们假设严重血吸虫发病率的关键生物学决定剂发生在每个阶段 寄生虫的生命周期：在人类寄主，在寄生虫中，在蜗牛宿主及其环境中。调查 这个假设，我们将使用两种研究设计：（i）LA和LV中的学龄前儿童（PSAC）的同类 探索免疫反应的早期演变，可能导致严重的发病率和（ii）成人病例控制 研究以识别与严重疾病有关的慢性暴露。我们还将收集寄生虫和蜗牛 两种设置的样本，并为未来的研究开发标本档案。我们的具体目标是 目标1。将早期生命免疫调查与LA和LV之间的SM暴露和感染进行比较并识别 调节SM特异性免疫反应和发病风险的共同曝光 AIM 2。建立一个在乌干达局部寄生虫局部遗传监测的平台，并确定 LA和LV的临床结果差异是否存在寄生虫遗传基础 目标3。确定生物掌菌的种群生物学决定剂。蜗牛充当本地 SM的流行病学驱动因素，过滤了其在LA和LV生态系统之间的多样性；是否 可用于检测生物掌和SM的环境（E）DNA特征 传输站点的蜗牛/寄生虫多样性以及关键人口组中感染风险 来自每个目标的数据将用于开发严重SM-驱动因素的全面，集成的模型 相关的发病率。该模型将进一步用于评估选定干预措施的可能收益， 并指导未来的预防和管理政策。