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

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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.