RFA-GH-22-001, Monitoring morbidity, evaluation of new diagnostic tools; interventions to reduce or interrupt transmission, and improving surveillance for intestinal schistosomiasis.

项目摘要/摘要 血吸虫病(SCH)表现为一系列的疾病，其中一些是常见的感染。 有两个物种(如贫血和生长受阻)，有些是物种特有的(例如， 曼氏血吸虫感染的肝肿大和血吸虫感染的肾积水)。 尽管近年来见证了大规模药物管理(MDA)用于SCH控制的规模扩大 在世界范围内，还没有采用单一的直接发病标志物来监测丙二醛的临床影响。 包括强有力的监测和评估(M&E)活动的适当的疾病监测仍然存在 这是确保疾病控制项目成功的关键因素。在任何位置的前面和中心 成功的监测工作需要新的和改进的诊断方法。不幸的是， SCH和土壤传播蠕虫病(STH)的诊断工具对人的敏感性较低 感染较轻，目前用于常规年度监测和评估的费用太高。 有效的诊断工具，对新治疗或配方和其他替代方案的药物警戒 包括灭螺在内的控制干预措施也仍然是阻断传播努力的核心。在……里面 为了达到监测发病率、评估新诊断的预期目标 减少或阻断传播的工具和干预措施，以及改善对S. Mansoni和STH在肯尼亚西部，提出了4组相互关联的研究。一个横截面 将利用调查设计来确定曼氏葡萄球菌(Sm)的感染水平， 或否，血吸虫病相关肝病发病率和血吸虫病防治监测指标 肯尼亚西部的锡亚县(Sm流行)和维希加(Sm非流行)县(目标1)。几个 将每年评估一次结果(粪便镜检、疟疾、贫血)，并在基线和中期进行评估 和学龄儿童的期末(腹部超声、肠道炎症)(SAC，8-14 青少年(≥14至18岁)和成年人(≥Y18至60岁)。作为监视工作的一部分 和M&E，目标2将确定洗涤战略的影响作为干预措施之一 肯尼亚卫生部NTD计划的突破传输战略(BTS)中的包在一个子 维希加县(洗手区)和霍马巴伊县(非洗手区)(目标2，目标1)。洗 与丙二醛对SCH和STH影响增加相关的水平将根据以下因素确定 精心设计的WASH问卷横截面发放给300名SAC(8-14岁)和 在基线、中期和中期，每个子县2个病房内的100名户主(18-60岁) 学习结束了。粪便和尿液样本将从同一SAC收集，每个SAC都有洗涤数据 时间点，并将用于评估曼氏葡萄球菌和STH的感染状态(加藤-卡茨用于粪便； 尿液的POC-CCA)。一种清洁评估工具，可以识别社区目标以帮助减少 流行率将得到验证。作为额外监测活动的一部分，存在、物种类型 血吸虫病中间钉螺媒介的传染性将在5个病房进行评估， 曼氏葡萄球菌在西部的卡卡梅加、邦戈马、维希加和跨尼佐亚等县的流行率最高 肯尼亚，以便为国家非传染性疾病控制方案的钉螺控制活动提供信息(目标2，目标 2)。对于目标3，目标1，通过上述目标1和2收集的样本子集将为 作为评价和验证尿液上转换颗粒侧向流动的材料 循环阳极抗原(UCP-LF-CAA)诊断血吸虫病的比较 标准的加藤-卡茨技术。对于目标3，目标2，通过以下方式收集的样本的子集 上述目标1和目标2将有助于为评价和 对目前开发的和未来的SCH和STH诊断技术进行验证。视情况而定 L-吡喹酮口腔分散片(阿吡喹酮)在婴幼儿中的推广应用 预计在2025/2026年获得注册批准)和提供资金，目标4的重点将是 目的：评价新药阿吡喹酮治疗慢性阻塞性肺疾病的疗效、影响和不良反应。 肯尼亚西部选定县的幼儿中的血吸虫病。结果来自于 拟议的工作包括关于评估曼氏葡萄球菌发病率的替代方法的数据， 评价肯尼亚卫生和环境卫生综合服务，数据，以指导控制钉螺的努力和对 改进了诊断工具和样本生物库。总体而言，这些成果不仅将推动 我们的知识，但也有助于实现疾控中心支持研究实施的目的 研究将提供有关监测、控制和潜在地消除 寄生虫病，包括SCH和STH，以期产生高度影响的公共卫生研究结果和 改进战略，减少寄生虫病的总体负担，增加 受影响人口的健康和福祉。

Project Summary/Abstract Schistosomiasis (SCH) presents with a range of morbidities, some of these are common to infection with either species (such as anemia and impaired growth) and some are species-specific (e.g., hepatomegaly in Schistosoma mansoni infections and hydronephrosis in S. haematobium infections). Although recent years have witnessed a scale-up of mass drug administration (MDA) for SCH control worldwide, no single direct morbidity marker has been adopted to monitor the clinical impact of MDA. Proper disease surveillance encompassing robust monitoring and evaluation (M&E) activities remains a key ingredient in ensuring the success of disease control programs. At the front and center of any successful surveillance efforts is the need for new and improved diagnostics. Unfortunately, the diagnostic tools for SCH and soil-transmitted helminthiasis (STH) can have low sensitivity in persons with light infections and are currently too expensive to use for routine annual M&E. In addition to effective diagnostic tools, pharmacovigilance for new treatments or formulations and other alternative control interventions including snail control also remain central in efforts to interrupt transmission. In order to arrive at the expected objective of monitoring morbidity, evaluation of new diagnostic tools and interventions to reduce or interrupt transmission, and improving surveillance for S. mansoni and STH in western Kenya, 4 sets of interconnected studies are proposed. A cross-sectional survey design will be utilized to identify infection levels of S. mansoni (Sm) below which there is little, or no, detectable schistosomiasis-associated liver morbidity and markers for M&E of SCH control in Siaya (Sm-endemic) and Vihiga (Sm-non-endemic) counties, western Kenya (Objective 1). Several outcomes will be assessed annually (stool microscopy, malaria, anaemia) and at baseline, mid-term and end-term (abdominal ultrasound, intestinal inflammation) among school-age children (SAC, 8-14 years), adolescents (≥14 to <18 years) and adults (≥y18 to 60 years). As part of surveillance efforts and M&E, Objective 2 will determine the impact of the WASH strategy as one of the intervention packages in the Kenya MoH NTD program’s Breaking Transmission Strategy (BTS) in one sub- County in Vihiga (WASH area) and Homabay(non-WASH area) counties (Objective 2, Aim 1). WASH levels associated with increased impact of MDA on SCH and STH will be determined based on carefully designed WASH questionnaires administered cross-sectionally to 300 SAC (8-14 years) and 100 household heads (18-60 years) within 2 Wards in each sub-County at baseline, mid-term and end of study. Stool and urine samples will be collected from the same SAC with WASH data at each timepoint and will be used to assess infection status for S. mansoni and STH (Kato-Katz for stool; POC-CCA for urine). A WASH assessment tool that can identify community targets to help reduce prevalence will be validated. As part of additional surveillance activities, the presence, species type and infectivity of intermediate snail vectors for schistosomiasis will be assessed in 5 wards with highest S. mansoni prevalence in Kakamega, Bungoma, Vihiga and Trans Nzoia counties of western Kenya so as to inform snail control activities for the National NTD Control program (Objective 2, Aim 2). For Objective 3, Aim 1, a sub-set of samples collected through Objectives 1 and 2 above will be used as materials for evaluation and validation of the urine Up-converting particle lateral flow circulating anodic antigen (UCP-LF-CAA) for diagnosis of schistosomiasis by comparing it with the standard Kato-Katz technique. For Objective 3, Aim 2, a sub-set of samples collected through Objectives 1 and 2 above will contribute to a sample biobank/repository for the evaluation and validation of currently developed and future diagnostic technologies for SCH & STH. Contingent on roll-out of L-praziquantel orodispersible tablet (arpraziquantel) treatment in young children (post- registration approval expected in 2025/2026) and availability of funding, the focus for Objective 4 will be to evaluate efficacy, impact and side effects of the new arpraziquantel for treatment of schistosomiasis in young children in select sub-Counties of western Kenya. Outcomes from the proposed work include data on alternative approaches for assessment of morbidity for S. mansoni, evaluation of the Kenya BTS for SCH and STH, data to guide snail control efforts and contribution to improved diagnostic tools and sample biobanking. Collectively, these outcomes will not only advance our knowledge, but also contribute to fulfilling CDC’s purpose to support implementation of research studies that will provide critical information on ways to monitor, control, and potentially eliminate parasitic diseases including SCH & STH, with a view to yield high impact public health findings and to improve strategies that will decrease the overall burden of parasitic diseases and increase the health and wellbeing of affected populations.