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

项目总结/摘要 血吸虫病（SCH）呈现出一系列的发病率，其中一些是常见的感染 与任一物种（如贫血和生长受损）相关，并且有些是物种特异性的（例如， 曼氏血吸虫感染者肝肿大和血吸虫感染者肾积水。嗜血杆菌感染）。 虽然近年来已经见证了大规模药物管理（MDA）的SCH控制的规模扩大， 在世界范围内，没有采用单一的直接发病率指标来监测MDA的临床影响。 包括强有力的监测和评价活动在内的适当的疾病监测仍然存在 这是确保疾病控制计划成功的关键因素。在任何一个 成功的监测工作需要新的和改进的诊断方法。可惜 SCH和土源性蠕虫病（STH）的诊断工具对人体的敏感性较低 轻度感染，目前过于昂贵，无法用于常规的年度M&E。除了 有效的诊断工具、新治疗或制剂的药物警戒以及其他替代方法 包括控制蜗牛在内的控制干预措施仍然是阻断传播的核心。在 为了达到监测发病率、评价新的诊断方法的预期目标， 工具和干预措施，以减少或中断传播，并改善监测S。 mansoni和STH在肯尼亚西部，4套相互关联的研究建议。的截面 调查设计将用于确定感染水平的S。mansoni（Sm），在其下方几乎没有， 或无，可检测到的染色体相关肝脏发病率和SCH对照的M&E标志物， 肯尼亚西部锡亚亚（钐流行）和维希格（钐非流行）县（目标1）。几 将每年评估一次结果（粪便显微镜检查、疟疾、贫血），并在基线、中期 学龄儿童中（SAC，8-14）和期末（腹部超声，肠道炎症 年龄）、青少年（≥14至<18岁）和成人（≥ 18至60岁）。作为监视工作的一部分 目标2将确定讲卫生运动战略作为一项干预措施的影响 肯尼亚卫生部NTD计划的突破传播战略（BTS）中的一个子项目， Vihiga县（讲卫生运动地区）和Homabay县（非讲卫生运动地区）（目标2，目标1）。洗 与MDA对SCH和STH的影响增加相关的水平将根据以下因素确定： 对300名SAC（8-14岁）进行了精心设计的讲卫生运动问卷调查， 基线、中期和中期每个县2个区的100名户主（18-60岁） 研究结束。将从同一SAC采集粪便和尿液样本，并在每个时间点采集WASH数据。 时间点，并将用于评估S. mansoni法和STH法（Kato-Katz法用于大便; POC-CCA用于尿液）。一个WASH评估工具，可以确定社区目标，以帮助减少 将验证流行率。作为额外监测活动的一部分， 将在5个病区评估血吸虫病中间媒介钉螺的感染性， 最高的S西部卡卡梅加、邦戈马、维希加和恩佐亚海峡县的曼索尼流行率 肯尼亚，以便为国家NTD控制方案（目标2， 2）。对于目标3，目标1，通过上述目标1和目标2收集的样本子集将 用作尿液上转换颗粒侧向流的评价和验证材料 循环阳极抗原（UCP-LF-CAA）诊断血吸虫病的初步研究 标准加藤-卡茨技术对于目标3，目标2，通过 上述目标1和2将有助于建立一个用于评价的样本生物库/储存库， 确认目前开发的和未来的SCH & STH诊断技术。取决于 在幼儿中推广左旋吡喹酮口腔分散片（arpraziquantel）治疗（治疗后 注册批准预计在2025/2026年）和资金的可用性，目标4的重点将 目的是评价新的Arpraziquantel治疗 在肯尼亚西部一些县的幼儿血吸虫病。的历史成果 建议的工作包括替代方法的数据评估的发病率为S。mansoni， 评估肯尼亚SCH和STH BTS，指导蜗牛控制工作的数据， 改进诊断工具和样本生物库。总的来说，这些成果不仅会促进 我们的知识，但也有助于实现疾病预防控制中心的目的，以支持研究的实施 这些研究将提供有关监测、控制和潜在消除 包括SCH和STH在内的寄生虫病，以期得出具有高度影响力的公共卫生结论， 改进战略，减少寄生虫病的总体负担， 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.