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.

总结 血吸虫病是一种被忽视的主要热带疾病，估计影响全球2.4亿人， 每年损失至少190万残疾调整生命年（DIFE）-其中90%的负担是在 撒哈拉非洲。在东非，乌干达在以下方面的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（U-SMRC） 在这一坚实基础上，发展一个充满活力的、以乌干达为主导的、以乌干达为基础的国际血吸虫病 该研究网络促进非洲变革性热带医学研究的能力。 乌干达是曼氏血吸虫（Sm）的高度流行地。肠道血吸虫病在许多村庄很普遍 围绕着五大湖和尼罗河。卫生部病媒控制司负责 长期以来，血吸虫病控制一直受到人们的关注， 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 吡喹酮大规模给药方案的可比传播情况。针对这一 关注，U-SMRC的核心研究目标是了解严重Sm的生物决定因素， 因此，我们需要进一步研究与此相关的发病率，并确定更好的预防和控制战略。 我们假设，严重染色体病的关键生物学决定因素发生在每个阶段， 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。探讨 基于这一假设，我们将使用两种研究设计：（i）LA和LV的学龄前儿童（PSAC）队列， 探索可能导致严重发病的免疫反应的早期演变;（ii）成人病例对照 研究确定与严重疾病相关的慢性暴露。我们也会收集寄生虫和蜗牛 从这两个设置的样本，并建立一个标本档案，为今后的研究。我们的具体目标是 目标1.比较LA和LV对Sm暴露和感染的早期免疫应答， 调节Sm特异性免疫反应和发病风险的共同暴露 目标2.在乌干达建立一个对寄生虫进行当地遗传监测的平台，并确定 是否存在导致LA和LV临床结局差异的寄生虫遗传基础 目标3.确定双脐螺属物种的种群生物学决定因素。蜗牛作为当地 Sm的流行病学驱动因素，过滤LA和LV生态系统内和之间的多样性;以及 来自双脐螺和Sm的环境（e）DNA特征的检测可用于更好地预测 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用于开发一个全面的，综合的模型，严重Sm的驱动程序， 相关的发病率。将进一步利用这一模式来评估选定干预措施的可能效益， 并指导今后的预防和管理政策。