Am. J. Trop. Med. Hyg., 103(Suppl 1), 2020, pp. 58–65 doi:10.4269/ajtmh.19-0825 Copyright © 2020 by The American Society of Tropical Medicine and Hygiene SCORE Operational Research on Moving toward Interruption of Schistosomiasis Transmission Carl H. Campbell Jr.,1* Sue Binder,1 Charles H. King,1,2 Stefanie Knopp,3,4,5 David Rollinson,5,6 Bobbie Person,1 Bonnie Webster,5,6 Fiona Allan,5,6 J¨urg Utzinger,3,4 Shaali M. Ame,7 Said M. Ali,7 Fatma Kabole,8 Eliezer ´ K. N’Goran,9,10 Fabrizio Tediosi,3,4 Paola Salari,3,4 Mamadou Ouattara,9,10 Nana R. Diakite, ´ 9,10 Jan Hattendorf,3,4 Tamara S. Andros,1 Nupur Kittur,1 and Daniel G. Colley1,11 1Schistosomiasis Consortium for Operational Research and Evaluation, Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia; 2Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio; 3Swiss Tropical and Public Health Institute, Basel, Switzerland; 4University of Basel, Basel, Switzerland; 5Department of Life Sciences, Wolfson Wellcome Biomedical Laboratories, Natural History Museum, London, United Kingdom; 6London Centre for Neglected Tropical Disease Research, Imperial College Faculty of Medicine, London, United Kingdom; 7Public Health Laboratory - Ivo de Carneri, Pemba, United Republic of Tanzania; 8Neglected Tropical Diseases Unit, Ministry of Health Zanzibar, Unguja, United Republic of Tanzania; 9Centre Suisse de Recherches Scientifiques en Coteˆ d’Ivoire, Abidjan, Coteˆ d’Ivoire; 10Unite ´ de Formation et de Recherche Biosciences, UniversiteF´ ´ elix Houphouet-Boigny, ¨ Abidjan, Coteˆ d’Ivoire; 11Department of Microbiology, University of Georgia, Athens, Georgia Abstract. As part of its diverse portfolio, the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) included two cluster-randomized trials evaluating interventions that could potentially lead to interruption of schistosomiasis transmission (elimination) in areas of Africa with low prevalence and intensity of infection. These studies, conducted in Zanzibar and Coteˆ d’Ivoire, demonstrated that multiyear mass drug administration (MDA) with praziquantel failed to interrupt the transmission of urogenital schistosomiasis, even when provided biannually and/or supplemented by small-scale implementation of additional interventions. Other SCORE activities related to elimination included a feasibility and acceptability assessment of test–treat–track–test–treat (T5) strategies and mathematical modeling. Future evalua- tions of interventions to eliminate schistosomiasis should recognize the difficulties inherent in conducting randomized controlled trials on elimination and in measuring small changes where baseline prevalence is low. Highly sensitive and specific diagnostic tests for use in very low–prevalence areas for schistosomiasis are not routinely available, which complicates accurate measurement of infection rates and assessment of changes resulting from interventions in these settings. Although not encountered in these two studies, as prevalence and intensity decrease, political and community commitment to population-wide MDA may decrease. Because of this potential problem, SCORE developed and funded the T5 strategy implemented in Egypt, Kenya, and Tanzania. It is likely that focal MDA campaigns, along with more targeted approaches, including a T5 strategy and snail control, will need to be supplemented with the provision of clean water and sanitation and behavior change communications to achieve interruption of schistosome transmission. INTRODUCTION AND OVERVIEW OF SCORE PORTFOLIO research on elimination of schistosomiasis. In addition to results IN ELIMINATION of the SCORE elimination study on Zanzibar funded with the original grant, two of the studies supported by the supplemental The Schistosomiasis Consortium for Operational Research funding are briefly described in this article—a multiyear field and Evaluation (SCORE) was started in late 2008 with a grant 1 study on interruption of seasonal transmission of Schistosoma from the Bill & Melinda Gates Foundation (BMGF). The SCORE haematobium in Coteˆ d’Ivoire and feasibility assessments of a portfolio contains several efforts designed to increase knowl- test–treat–track–test–treat (T5) strategy in Egypt, Kenya, and edge about how to move from morbidity control toward elimi- Tanzania. nation of schistosomiasis. The initial grant included funding for a The main objective of this study was to provide an overview fi eld study comparing approaches to elimination, which became and summary of the SCORE-funded efforts pertaining to moving the Zanzibar elimination study, described in the following sec- toward elimination (interruption of schistosomiasis transmission). tion. The grant also included support to develop and test better These include the following: tools for mapping of Schistosoma mansoni infections and for a fi test with high sensitivity and speci city that would allow for di- 1. the Zanzibar elimination study; agnosis of schistosomiasis in an individual with a high degree of 2. the S. haematobium seasonal transmission elimination fi con dence. These tools are needed to move toward interruption study in Coteˆ d’Ivoire; ’ of schistosomiasis transmission (elimination). SCORE sworkon 3. the T5 strategy; and developing and evaluating mapping and diagnostic tools is de- 4. modeling using SCORE data. scribed in other articles in this supplement.2,3 In 2012, the World Health Assembly (WHA) issued resolution Additional intervention studies were planned for Burundi WHA 65.21, which called for the expansion of schistosomiasis and Rwanda, where only S. mansoni is endemic. Unfor- control programs and to “initiate elimination campaigns where tunately, after countrywide mapping was completed in each appropriate.”4 Following this, in 2013, SCORE received sup- country,2,3 the studies could not be implemented because of plemental funding from the BMGF to build on data and experi- the lack of high-level support in Rwanda and political in- ences obtained by SCORE thus far and expand operational stability in Burundi. However, the mapping surveys yielded invaluable data about the performance of both the point-of- care circulating cathodic antigen (POC-CCA) urine cassette * Address correspondence to Carl H. Campbell Jr., Schistosomiasis Consortium for Operational Research and Evaluation, University of test and the laboratory-based up-converting phosphor-lateral Georgia, 145 Coverdell Center, 500 D.W. Brooks Dr., Athens, GA flow circulating anodic antigen (UCP-LF CAA) assay in areas – 30602. E-mail: [email protected] of low prevalence.5 7 58 SCORE ELIMINATION OPERATIONAL RESEARCH PORTFOLIO 59 The Zanzibar elimination study. Background. In July 2009, MDA + snail control, and biannual MDA + behavior change the SCORE secretariat convened a meeting to inform the interventions. Each study arm included 15 shehias on Unguja design of the SCORE schistosomiasis elimination study and and 15 on Pemba, for a total of 90 shehias.9 Interventions were brainstorm about where such a study might be conducted. conducted for 5 years, starting in 2012 and ending in 2017.14 The discussions covered both elimination of transmission The main study outcomes were prevalence and intensity at (zero new infections) and elimination as a public health prob- Year 6 (2017) among 9- to 12-year-old children.15 Annually, lem, as defined by the World Health Organization (WHO).8 efforts were made to survey 100 children aged 9–12 years in Participants developed the criteria for potential study each of the 90 study schools with a single urine filtration for the sites, including a starting prevalence low enough that elim- presence and number of S. haematobium eggs. The statistical ination could be considered a next step, but not so low that analysis plan for Zanzibar is included as a Supplemental file the study would focus on issues around verification of the (S1). Additional results available in other publications include interruption of transmission; adequate population size; re- urine prevalence and intensity among adults, first-year stu- cent experience with mass drug administration (MDA); ca- dents at the baseline and at the end point, and schistosome pacity to conduct research; and high-level political will. population genetics.14–16 Interventions discussed included MDA, implementation of Mass drug administration. Biannual MDA was conducted by water and sanitation improvement, snail control, and edu- the NTD Program of the Ministry of Health Zanzibar, according to cation and behavioral change efforts. the National Plan.9 Several issues were encountered related to After this meeting, to find the optimal study site, SCORE the implementation of MDA. These included delays in program reviewed documents, held discussions with neglected tropical funding and difficulty coordinating MDAs with school schedules disease (NTD) control leaders, and visited Botswana and and local events.17,18 Nevertheless, coverage among students in Uganda. Candidate countries were removed from consideration study schools on Pemba was above 75% in all years. On Unguja, for several reasons, such as the lack of political commitment in coverage was below 75% in years 1 and 2, but reached 97% in Botswana, and concerns about relevance or acceptability in year 3.16,19 Africa of results were the study to be conducted in the Americas. Snail control. From 2012 to 2017, human–water contact Zanzibar was a strong candidate for the study because of sites (HWCS) in shehias in the snail control arm were surveyed