Uganda Schistosomiasis Multidisciplinary Research Centre (U-SMRC)

摘要 血吸虫病是一种被忽视的主要热带疾病，估计在全球范围内影响2.4亿人，居 每年至少损失190万个伤残调整生命年(DALY)--这一负担的90%来自 撒哈拉非洲。在东非，乌干达在开创性研究和伙伴关系方面有着良好的记录 血吸虫病研究。乌干达血吸虫病多学科研究中心将 在这个坚实的基础上发展充满活力的、乌干达主导的、以乌干达为基础的国际血吸虫病 促进非洲热带医学变革研究能力的研究网络。 乌干达是曼氏血吸虫高度流行的国家。肠道血吸虫病在许多村庄很普遍 在五大湖和尼罗河周围。卫生部病媒控制司(VCD)，负责 对于血吸虫病的控制，长期以来一直对日本严重血吸虫病的高发病率感到担忧 西北阿尔伯特湖地区(LA)，与中部和东部维多利亚湖地区(LV)相比，尽管 吡喹酮大规模药物管理的可比传播和方案。作为对此的回应 令人担忧的是，U-SMRC的核心研究目标是了解严重Sm的生物学决定因素。 与此相关的发病率，并确定更好的预防和控制战略。 我们假设严重血吸虫病发病的关键生物学决定因素发生在血吸虫病的每个阶段 寄生虫的生命周期：在人类宿主中，在寄生虫中，在蜗牛宿主及其环境中。去调查 在这一假设下，我们将使用两个研究设计：(I)洛杉矶和LV的学龄前儿童(PSAC)队列，以 探索可能导致严重发病率的免疫反应的早期进化和(Ii)成人病例对照 确定与严重疾病相关的慢性暴露的研究。我们还将收集寄生虫和蜗牛 从这两个环境中收集样本，并为未来的研究建立一个样本档案。我们的具体目标将是 目的1.比较LA和LV对Sm暴露和感染的早期免疫反应并确定 调节Sm特异性免疫反应和发病风险的联合暴露 目的2.建立乌干达血吸虫地方遗传监测平台，确定 LA和LV的临床结局差异是否有寄生虫遗传基础 目的3.确定Biomphalaria spp.的种群生物学决定因素。蜗牛扮演当地人的角色 Sm的流行病学驱动因素，过滤其在LA和LV生态系统内和之间的多样性；以及 从Biomphalaria和Sm中检测环境(E)DNA特征可以用来更好地预测 传播地点的蜗牛/寄生虫多样性和关键人口群体内的(再)感染风险 来自每个目标的数据将被用来开发一个全面、综合的严重Sm-M驱动因素模型。 相关发病率。该模型将被进一步用于评估选定干预措施的可能益处， 并指导未来的预防和管理政策。

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.