Schistosoma mansoni, and increasing the sensitivity of a laboratory-based diagnostic. SCORE also supported studies on morbidity due to schistosomiasis, quantification of vector snails and the detection of schistosome infections in snails, and changes in schistosome population genetics under praziquantel drug pressure. SCORE data and specimens are archived and will remain available for future research. Although much remains to be carried out, our hope is that through the already published articles and SCORE results described in this supplement, we will have provided a body of evidence to assist policy makers in the development of judicious guidelines for the control and elimination of schistosomiasis.The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in late 2008 to conduct operational research that would inform practices related to the control and elimination of schistosomiasis. This article traces SCORE’s beginnings and underpinnings. These include an emphasis on openness and contributing to the development of a cohesive schistosomiasis control community, building linkages between researchers and national programs, and focusing on answering questions that will help Neglected Tropical Disease program managers to better control and eliminate schistosomiasis. It describes the development and implementation of SCORE’s multiple projects. SCORE began by drawing on advice from a broad range of experts by holding wide-ranging meetings that informed the priorities and protocols for SCORE research. SCORE’s major efforts included large, multicountry field studies comparing multiple strategies for mass drug administration with praziquantel, assessment of approaches to elimination, evaluation of a point-of-care assay for field mapping  American Journal of Tropical Medicine and Hygiene, which summarize many of the findings and lessons learned through SCORE studies. The final article in this supplement looks to the future—providing the thoughts of the SCORE secretariat—with input from the research consortium and its partners, regarding where SCORE will leave off and what will hopefully follow.1This article is being written on the 10-year anniversary of the establishment of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) and as the SCORE project nears completion. It describes the context in which SCORE was developed and the conceptual basis on which it was founded. It also lays the groundwork for subsequent articles in this supplement to the 2 This article sought to provide a comprehensive and cohesive summary of critical needs in schistosomiasis research. It drew from the agendas of existing programs, such as those at the WHO and the U.S. National Institute for Allergy and Infectious Diseases (NIAIDs) of the NIH, and input from people around the world. Ideas and comments were solicited from more than 350 people, and more than 150 people actually contributed.In December 2007, Daniel Colley and Evan Secor published an article entitled “A Schistosomiasis Research Agenda.”The goals of the agenda development process and publication included increasing interactions among the schistosomiasis community, which until then, was perceived as highly fragmented, and stimulating interest of funders to address critical research needs. Colley and Secor hoped that the process for developing the agenda—which was highly interactive—and its publication would lead to more interdisciplinary networks focused on schistosomiasis research, standardization of protocols for multicenter studies, increased use of repositories, recruitment of trainees, enhanced mentoring of junior researchers, enlistment of outside experts into schistosomiasis work, and a higher profile for schistosomiasis research that would lead to development and adoption of evidence-based approaches to control by the global health community. In regard to increasing funding, the hope was that investigators and funding organizations would respond to a community-generated, comprehensive agenda by identifying particular areas in the agenda in which they could participate and provide support.In September 2007, while the agenda manuscript was “in press,” Colley made an invited presentation about the schistosomiasis research agenda at a workshop at the NIAID. In his presentation, he suggested that different funders focus on different parts of the agenda. For example, NIAID should focus on various basic research aspects, whereas others should fund operational research. Julie Jacobson, senior program officer of the Infectious Diseases program at the Bill & Melinda Gates Foundation (BMGF), was in the audience.2 showed the potential to focus the next investments to build on progress of previous investments in a more comprehensive way and, thus, to speed progress and build the needed evidence base for programs. The approach used by the BMGF on lymphatic filariasis (LF) seemed a good model to operationalize the research agenda, with multiple researchers aligned around shared, programmatically relevant goals. Colley’s work on the schistosomiasis research agenda, strong standing in what was thought of as a fragmented schistosome research community, and collaborative nature made him an excellent choice to apply a consortium approach to the operational research considered necessary to enhance control and move toward possible elimination of schistosomiasis.Previously, the foundation had funded large field programs as independent investments in multiple neglected tropical diseases (NTD), including schistosomiasis , as exploratory one-time investments. Although this approach resulted in some very important early programmatic findings, the BMGF did not consider this the best way forward to address the interrelated needs of control programs, including to bolster much needed evidence-based guidance and share findings collaboratively among multiple, broadly based researchers. The collaborative approach taken by the Schistosomiasis Research AgendaSchistosoma mansoni and Schistosoma haematobium. The emphasis would be on research that was likely to have a major impact on schistosomiasis control and elimination in a relatively short time frame as programs were just starting to scale up. Research on vaccines and new pharmacologic treatments, which was thought unlikely to impact control programs in the short term and direct work on Schistosoma japonicum, was explicitly excluded from the effort Jacobson was proposing. Furthermore, this program would work with existing NTD control programs when possible and would make an effort to engage the broad schistosomiasis community.On January 9, 2008, Jacobson called Colley at the University of Georgia (UGA), where Colley was the director of the Center for Tropical and Emerging Global Diseases, to discuss BMGF interest in having him lead a large operational research effort related to schistosomiasis, focused on Following that discussion, SCORE began to take shape. In mid-February, the office of the President of UGA awarded Colley a developmental grant to support continued engagement with the broad schistosomiasis community, further define the most critical questions for SCORE to address, and garner ideas about how to structure a research consortium that could implement the range of studies potentially to be funded by a BMGF grant. Six meetings and multiple discussions with a wide spectrum of leaders from the schistosomiasis research and control communities, including the WHO, led to a consensus that the field studies would be largely based in Africa and would be most likely carried out through North–South partnerships involving both researchers and NTD program managers.Colley submitted the SCORE Letter of Intent to the BMGF on April 11, 2008, and it was accepted on June 2. The final proposal was submitted on September 15, 2008 at about the same time as the 2008 global financial crisis was forcing many funders, including the BMGF, to re-examine the extent and priorities of their investments. Jacobson remained a staunch supporter of the SCORE proposal and argued hard for the BMGF to support its objectives, believing in the high potential for impact, increased program efficiency, and alignment with the BMGF commitment to equity. In late November, the BMGF funded SCORE through the UGA Research Foundation, Inc. with a 5-year, $18.7 million grant. This represented an enormous commitment to schistosomiasis operational research, funding work that had not been and was unlikely to be funded by others. The BMGF has continued its support for SCORE for more than 10 years, including a June 2013 funding supplement focused on research related to elimination of schistosomiasis and multiple no-cost extensions.3 Although specific schistosomiasis control measures, such as environmental changes that reduce snail habitat and the general effects of improved sanitation, had markedly reduced or eliminated schistosomiasis in some places, population growth and development projects, such as irrigation systems and dams, appeared to be exacerbating the problem in others.5In 2009, it was estimated, based on a systematic review that used data from 2003, that 779 million people were at risk for schistosomiasis and more than 200 million were infected.6 was preventive chemotherapy through mass drug administration (MDA) of praziquantel (PZQ), largely through schools, with a focus on morbidity control as defined by WHO, that is, reduction in high-intensity infections. SCI, funded by the BMGF, had recently demonstrated in several countries that MDA for schistosomiasis could be rolled out on a countrywide basis, given sufficient funding, country commitment, and good management.7 Nevertheless, there was recognition that significant functional morbidities were impacting infected individuals who did not have high-intensity infections, and most people at risk were not receiving treatment.8 Utzinger et al.9 estimated that treating all 128 million African children thought to be at risk for schistosomiasis according to the WHO guidelines would require between 192 and 384 million PZQ tablets every year.The mainstay of schistosomiasis control programs, based on WHO guidelines from 200111 and on treatment of schoolchildren and not generally adults.The WHO guidelines were written at a time when PZQ was scarce and very expensive, and disease burden was relatively high. Therefore, they focused on controlling morbidity due to chronic heavy infections leading to severe disease, such as portal hypertension, hepatosplenomegaly, and carcinoma of the bladder,Propitiously, beginning in 2009, Merck KGaA  pledged to donate 200 million tablets annually of PZQ for 10 years through WHO for countries to implement national programs to control morbidity due to schistosomiasis, mainly in school-aged children in sub-Saharan Africa. Then in 2012, as part of the London Declaration, the company pledged to incrementally increase their donation to reach 250 million tablets per year by 2016 and to continue at that level until 2020 in support of the WHO NTD Roadmap goals. The confluence of the findings by SCI that nationwide MDA was possible and this major donation of PZQ by Merck KGaA provided the impetus and opportunity for operational research such as that being proposed for SCORE into what might be the best MDA strategies, as well as other approaches and tools that could help decrease transmission and measure impact of interventions.12 which were expected to be more cost-efficient than stand-alone programs. With the support of Jacobson, it was decided that research within SCORE would focus on control and elimination of only schistosomiasis, although testing for soil-transmitted helminths (STH) would be included in studies of S. mansoni where it would not disrupt the schistosome-focused study design, and MDA for STH would be included where appropriate. The thinking behind this was that schistosomiasis poses several challenges for integration, and first determining how best to reduce schistosomiasis on its own would provide a better understanding of how to integrate schistosomiasis control into broader programs. Also, it was decided that study sites would be the areas with either S. mansoni or S. haematobium, but not mixed infections.At the time the SCORE studies were being developed, the prevailing concept was that control of NTDs would be best carried out through integrated programs,SCORE was managed by a very small Secretariat, which included individuals with a range of experiences and skills. At its maximum, the Secretariat included seven people, only two of whom were full-time.An Advisory Committee to the SCORE secretariat was established, consisting of Paul Hagan, Stephanie James, Stephen McGarvey, Eric Ottesen, and Joseph Cook. First, Lorenzo Savioli, and then Dirk Engels and subsequently Gautam Biswas, the directors of the WHO/NTD program, graciously committed to always having someone in the WHO/NTD group serve as an ad hoc member of the SCORE Advisory Committee, thus ensuring a strong connection between SCORE’s studies and activities and the WHO/NTD team. First Lester Chitsulo and then Amadou Garba served in this capacity.Very quickly after being funded, during 2009, SCORE held a series of seven expert panels to identify and explore research priorities for what were considered the most critical questions on the control and elimination of schistosomiasis. The topics for meetings, dates they were held, and numbers of attendees are listed in 13 There were often strong disagreements, but these grew out of a shared desire for a deeper understanding of the issues and a commitment to making the SCORE research as good and meaningful as possible.These seven meetings (and a subsequent one on snail control in 2013) were essential for the development of the protocols that were the basis of the multiple studies pursued by SCORE. The underlying premise on which all the protocols were eventually based was whether the answers from the research would be likely to help a program manager do his or her job better. Meetings were highly interactive, with excellent participation by all. Discussions centered around scientific/programmatic issues, but by necessity also included political and security issues as well as costs and other practicalities.The expert panel meetings resulted in outlines of priority studies. These were subsequently refined by SCORE secretariat into draft requests for applications (RFAs), most of which were reviewed by the SCORE Advisory Committee and other colleagues before being finalized. The final RFAs were sent to investigators with track records in similar operational research. For the large studies on gaining and sustaining control, a critical requirement was the buy-in of the national NTD programs of the countries where the proposed studies would be conducted.Multiple applications were received. These were evaluated by the Secretariat with assistance from the SCORE Advisory Committee and funding decisions made. From 2009 to 2018, a total of 48 sub-awards, some with multiple activities added during the years, have been made through SCORE.S. mansoni, with other research quickly following. The portfolio evolved, both as a result of early findings from SCORE and other studies and from new priorities from the BMGF.As noted earlier, the guiding principle by which studies were considered and designed was based on the simple question: “What strategies and tools will help NTD program managers do their job better?” Because in 2009, the mainstay tool was MDA with PZQ, the SCORE research portfolio initially focused on large field studies of alternative approaches to MDA and field evaluation of a mapping tool for An attempt by SCORE to conduct a meta-analysis of studies on control of schistosomiasis found a scarcity of randomized trials and other quality studies that compared approaches with achieving reductions in schistosomiasis prevalence and intensity. This reinforced the need for better data on the impact by alternative approaches. Thus, a high priority for SCORE was research on how best to use what were, at the time, limited supplies of PZQ—whether through community-wide treatment (CWT) or school-based treatment (SBT) and whether to treat more villages by doing MDA every other year, with the year off being referred to as “drug holiday.” Such data were needed for planned revisions of the WHO guidelines related to schistosomiasis control, and to provide an evidence base for new thresholds for action and recommended interventions.An issue raised in SCORE’s expert panel meetings was whether it was ethical to use approaches to MDA that were inconsistent with the existing WHO guidelines. Chitsulo, the WHO ad hoc member of SCORE’s Advisory Committee at the time, noted that the guidelines were based on little hard evidence and needed a scientific basis. Given that the benefits of annual MDA versus every-other-year had not been established, and that it was unclear if a program would provide more benefit by treating twice as many communities every other year versus a smaller number annually, the inclusion of holidays was thought by the participants to be ethical. Chitsulo said, “You cannot evaluate the guidelines if you go by the guidelines.”In addition, it was noted that all studies would be reviewed by human subjects review boards, including boards in-country. Also, after the final data collection, all villages were to be receiving MDA; so at the end of the study, each participating village would have had at least two consecutive rounds of MDA.Other issues discussed included the prevalence cutoffs to be used, treatment of adults in villages receiving CWT and the frequency of the MDA.14 These studies were carried out in five African countries: Côte d’Ivoire, Kenya, Mozambique, Niger, and Tanzania. The protocols for these studies involve various combinations of community-wide MDA, school-based MDA, and drug holidays over a period of 4 years, followed by final data collection in the fifth year. The primary outcome of interest was change in prevalence and intensity of schistosomiasis among children ages 9–12 years. Data were also collected at given times on incoming first-year students (ages 5–8 years) and adults from 20 to 50 years of age. In addition, data were collected on factors that might prove useful in predicting a community’s response to MDA, such as village-level data about sanitation, occupations, population shifts, snail infections and abundance, and changes in schistosome population structure under drug pressure. Other articles in this Journal supplement address the results of the large field studies on gaining and sustaining control of schistosomiasis.17The goal of developing data that would evaluate current guidelines and contribute to new, evidence-based guidelines led to SCORE’s largest field studies, referred to as the SCORE “gaining and sustaining control studies.”One challenge that SCORE overcame with the help of partners was related to the supply of PZQ for these large field studies. Praziquantel was needed for 4–5 rounds of MDA  in 825 villages in the five countries. Because WHO/NTD initially promised to supply the PZQ needed for these studies, the SCORE proposal to the BMGF did not request funds for PZQ. Unfortunately, the WHO/NTD program could not deliver on their promise. Graciously, programs funded through SCI, the United States Agency for International Development, and the Department for International Development of the United Kingdom came to the rescue in the different countries. Although it took considerable discussion, there were times when SCORE was able to convince one NTD program manager in one country to provide expiring PZQ to another program manager in another country that needed PZQ for their SCORE study. One positive result of this change in the sources of PZQ in some countries was stronger links between the research programs and the national control programs that were managing the PZQ donations—an important aspect of these studies.18The expert panel meeting on subtle morbidity reflected the state of the field. This included recognition that infected individuals without high-intensity infections could also experience significant morbidity, and that the commonly used parameters to measure subtle morbidity in schistosomiasis were not reliably indicative of the attributable fraction of morbidity actually due to schistosomiasis. Nevertheless, measurements were selected for study in cohorts of children entering the gaining control studies in Mozambique, Niger, Kenya, and Tanzania. Comparisons would be between children in villages in the arms with what was expected to be the most intensive MDA  versus villages in the arms that would receive substantially less intervention . The potential morbidity markers to be measured included anthropometric measures, abdominal or urogenital ultrasounds, measures of fitness and/or volitional activity, anemia, and quality of life.S. haematobium after treatment and how much benefit was added by two closely spaced PZQ MDAs versus a single MDA. Some of the RAPs that were developed provided findings to be tested in the larger SCORE field studies. This approach of synthesizing the existing literature on a focal topic pertinent to control has led to seven completed RAPs.19During the meetings of expert panels, participants described many questions they were being asked by program managers that likely had answers in the existing literature. In 2009, SCORE initiated the RAPs. Questions included whether adults could become reinfected with 20 The first challenge in this effort was where in sub-Saharan Africa an elimination study could be conducted. After an extensive process, the archipelago of Zanzibar was selected as the study site. Many factors contributed to this selection, including clear geographic boundaries; strongly stated political support, including from the President of Zanzibar; commitment to biannual MDA by the Ministry of Health and partners; and other resources available on the islands.The purpose of the SCORE elimination studies was to conduct research on what integrated strategies might be able to stop transmission and achieve elimination.21 Colley had concerns about whether the broader community would accept the results of research on schistosomiasis elimination on islands as having general applicability. The late Likezo Mubila of WHO/Regional Office for Africa convinced Colley otherwise, providing persuasive insights and fully supporting SCORE’s investment in Zanzibar. Similar concerns were raised at the BMGF. However, a consensus was reached and plans for research on elimination on Unguja and Pemba, the main islands of Zanzibar, moved forward. Subsequently, as SCORE and partners, such as the Ministry of Health, SCI, the Natural History Museum (NHM), and the Swiss Tropical Public Health Institute were planning the research studies; a collaboration of a wide range of multiple agencies and investigators was created, which called itself Zanzibar Elimination of Schistosomiasis Transmission.23 The SCORE Zanzibar Elimination Study became the research component of this collaborative effort.The decision was difficult. Based on his early experience in the 1970s with the Research and Control program on St. Lucia,24 In keeping with this resolution and the adoption of the WHO NTD Roadmap goals in the London Declaration, in June 2013, the BMGF provided SCORE with an additional $3,468,375 and an extension of the project to December 31, 2017 to conduct supplemental work on elimination and other projects evolving from SCORE findings.In May 2012, the World Health Assembly (WHA) issued WHA Resolution 65.21 that called for the expansion of schistosomiasis control programs and to “initiate elimination campaigns, where appropriate.”S. mansoni transmission, 2) evaluate approaches to elimination of S. haematobium in areas with seasonal transmission, 3) conduct operational research on innovative approaches to snail control, 4) conduct additional RAPs to synthesize the existing literature to provide guidance for programs about use of niclosamide and about use of sanitation measures, and 5) conduct meetings to develop sampling schemes and tools to assess progress towards and achievement of elimination.The objectives of this supplement were to 1) evaluate approaches to elimination of S. mansoni transmission. Unfortunately, after extensive mapping, the planned S. mansoni intervention studies were ultimately not completed in either Rwanda because of lack of national government buy-in or Burundi because of civil unrest. However, the extensive mapping by Kato–Katz, the point-of-care circulating cathodic antigen (POC-CCA) assay, and, in a subset of specimens, the up-converting phosphor lateral-flow circulating anodic antigen (UCP-LF CAA) (see below) provided critical information about performance of both Kato–Katz testing and POC-CCA in an area of low prevalence and reinforced the message that there was more schistosomiasis in many “low-prevalence” areas than had previously been believed.26One objective of the supplement was to evaluate approaches to elimination of S. haematobium, which is currently being completed in Côte d’Ivoire and incorporates both MDAs and snail control, with timing of these two interventions based on the seasonality of transmission.28 In addition, in regard to snail control, SCORE held a meeting focused on various potential approaches as well as mollusciciding. SCORE also then pursued several studies on predatory crustaceans.29The supplement also led to a major field study, the Seasonal Elimination Study on It was clear that to control schistosomiasis to moderate or low levels of prevalence and intensity of infection more sensitive mapping tools were needed, as well as a test that would be both highly sensitive and highly specific. The previously mentioned 2009 meeting on diagnostics included both individuals working with parasite diagnostics and those using cutting-edge technologies for other purposes . The discussions included tools for mapping, but largely focused on possible diagnostics with very high sensitivity and specificity.Many laboratories that had developed “boutique assays” for research mapping and diagnostics that they used in their own studies or perhaps were used by one or two other groups in collaboration hoped that SCORE would be able to provide support. Unfortunately, SCORE was not funded for product development and, therefore, did not have the funding, the technical staff, or time needed to develop and evaluate new mapping tests that were not ready or near-ready for field work.S. mansoni was commercialized and made available for purchase . This assay uses monoclonal antibodies to detect a glycan (circulating cathodic antigen) vomited by adult worms into the blood stream, cleared in the kidneys, and detectable in urine.30 The assay is not only more sensitive than the Kato–Katz assay for S. mansoni at low prevalence but it also obviates the need for collecting stools and for trained microscopists. Although it appeared to perform well in laboratory and small-scale field settings, it had not been extensively evaluated in the field in endemic areas with different levels of prevalence and intensity of infections. The SCORE Five-Country Study, which compared the POC-CCA versus the Kato–Katz assay, and several subsequent investigations are summarized in the article on the POC-CCA.31Shortly before SCORE was funded, the POC-CCA urine assay for S. haematobium32; however, there was no new field assay for S. haematobium near ready for field-testing. SCORE’s portfolio did not include product development; therefore, a mapping tool to replace the urine dipstick for hemoglobin or microscopy-based urine filtration for S. haematobium eggs was not pursued. Later, limited resources were used to try to refine and test S. haematobium–mapping tools, but these attempts did not work well enough to warrant further investment of project funds.At the time, it was already recognized that the POC-CCA was not useful for mapping for S. mansoni and S. haematobium adult worms, the CAA.33 The specific goals of SCORE support were to make the UCP-LF CAA assay as sensitive as possible, in hopes of being able to detect single-worm infections, and to evaluate its potential as a confirmatory assay for proof of cure or lack of infection. The envisioned uses of the assay included assessing the results of field tools such as the POC-CCA, accurately measuring prevalence and intensity as places approach elimination, and determining whether PZQ treatment was curative in an individual. Results of the SCORE investment in UCP-LF CAA development and findings from its use in SCORE studies are summarized later in this supplement.34Regarding the highly sensitive and specific diagnostic, discussions at the 2009 meeting covered a range of approaches, including nucleic acid, antigen, and antibody tests. It was decided that SCORE would support the further development of the laboratory-based UCP-LF CAA assay, housed at the Leiden University School of Medicine. This sensitive assay detects a different glycan antigen than that detected by the POC-CCA but is also produced by both 35 and the Zanzibar Elimination Study, and eventually the Seasonal Elimination Study in Côte d’Ivoire.29In addition to diagnostics for humans, diagnostics for snails could be critical for evaluating elimination efforts and assessing force of transmission in studies of gaining and sustaining control. Although initially SCORE planned to invest in snail diagnostic test development, the SCORE meeting of experts concluded that existing methods were adequate for SCORE purposes. Furthermore, it was thought that other research funding, for example, for development and validation of loop-mediated isothermal amplification techniques would likely provide useful tools for such xenomonitoring by the time they would be needed for future elimination programs. Rather than focusing on development of more or better tools for snail infection detection, SCORE layered snail collection studies that included measurement of patent infections within some of the gaining control studiesWhile the need for research on most of the topics selected by SCORE was somewhat self-evident, there was considerable early discussion about the inclusion of schistosome population genetics, primarily about whether such work was too much in the realm of “basic science” for SCORE. The ultimate decision to support schistosome population genetics research was based on the concern that if drug resistance could not be detected until it could be measured clinically, it would be too late to ensure the continued utility for PZQ–the only drug currently being used to treat schistosomiasis. Therefore, schistosome population genetics studies were designed to provide insights into potential changes in schistosome population structures under varying levels of MDA pressure. Should changes occur, the hope was that measurement of these changes could be developed into an early warning system for potential PZQ resistance.S. mansoni was published, adequate information about microsatellites (the tool at the start of these studies) was available to characterize S. mansoni. However, there was much less experience with S. haematobium microsatellites. With SCORE support, a consortium involving UGA, the NHM , and Centro de Pesquisas “Rene Rachou”/FIOCRUZ  conducted low-coverage genomic sequencing to identify thousands of microsatellite loci from a recent field isolate of S. haematobium from Zanzibar.36Because the genome of 37 Also, the collected specimens will provide rich material for analysis for years to come.As part of some of SCORE’s gaining control studies and the Zanzibar elimination study, well-characterized cercarial and miracidial specimens were collected and banked  in anticipation that over time costs would fall and better gene sequencing methodology would be developed. Genetic analyses were subsequently initiated. The information yielded thus far has contributed in several different and somewhat unexpected ways that are summarized in the article by Webster et al.38 is housed at the NHM. Adrian Emery is the principal investigator and curator of SCAN. In addition to the vast number of specimens of both schistosome DNA and snails from the SCORE studies, SCAN has now obtained many specimens from other projects and provides an in-and-out repository service for investigators in the schistosomiasis community.The inclusion of schistosome genomic studies led to another contribution by SCORE. The banking of specimens described above and of snail specimens from SCORE and other studies was possible because of the funding by the Wellcome Trust of a joint proposal from the NHM and SCORE. The Schistosomiasis Collection at the NHM (SCAN)27Several changes previously mentioned impacted the course and priorities of SCORE. For example, as mentioned, the increase in interest in the schistosomiasis community in elimination led to the supplemental funding and projects aforementioned and in another publication in this supplement.Some issues of great concern at the time SCORE was planned are less so now. The push for integration of NTD control programs became more refined as the NTD community learned more about what elements were best integrated. Programmatic drug distribution in the case of schistosomiasis became linked to STH programmatic distributions through schools, but it is less often combined with other programs because of differences in delivery platforms and targeted age groups, the often focal nature of schistosomiasis, and the inclusion of drug holidays based on levels of prevalence.39Technologic developments also impacted SCORE. The banking of schistosome specimens for later genomic testing was described previously. The major gaining and sustaining control studies were initiated as phone-based data collection was beginning to take hold, replacing paper-based data and use of personal digital assistants. During this time of transition in data collection, the five countries involved in gaining and sustaining control studies used three different approaches to data collection: paper-based, a phone-based system developed by the EpiCollect group at Imperial College, and a phone-based system developed using the Open Data Kit. The challenges associated with this are described in the supplement article on recommendations.It also became clear about midway through SCORE that a bigger effort was needed to standardize the way SCORE field studies reported data to the Secretariat and the way the large field studies analyzed data. This led to the development of the SCORE Uniform Data System and Statistical Analysis Plans.S. mansoni studies, instead of the single stool that would be collected in a typical program. When research team vehicles were used to deliver PZQ, costs also were higher than those from routine programs.A high priority for SCORE was assessing not just the effectiveness of the interventions related to gaining and sustaining control but also the costs of their implementation. With the help of economists experienced in conducting NTD cost-effectiveness evaluations, SCORE included a cost assessment in the second or third year of each of the studies of gaining and sustaining control. Some of the difficulties in conducting these were recognized in advance, such as the difficulty of distinguishing between program and research costs. For example, SCORE studies required collection of three stool specimens among 9–12-year-old children in the 40 where on-site training was provided, the data quality was good, but the costs were deemed not relevant for program purposes because of the use of the high-cost research infrastructure from CDC’s presence at the Kenya Medical Research Institute.Unfortunately, the instructions for data collection were not uniformly followed, some of the data could not be analyzed, and other results could not be explained except by assuming the data were faulty. In Kenya’s gaining control study,S. mansoni. The Five-Country Study about the POC-CCA and subsequent studies by SCORE43 and others44 clearly showed that the Kato–Katz assay underestimated the number of people infected with S. mansoni, especially in areas with less than 50% prevalence by the Kato–Katz assay.Major changes in thinking have resulted from the data being generated by SCORE, for example, related to the POC-CCA urine assay for 46Although many published articles had previously shown that the Kato–Katz assay, while highly specific, has quite low sensitivity in areas with low or moderate prevalence and intensity of infection, the finding of so much more schistosomiasis than expected raised multiple issues related to how to control and eliminate schistosomiasis. SCORE redirected funds to answer some of the critical questions, for example, whether people who are trace-positive by POC-CCA in areas of very low prevalence contribute to transmission.17 and have been detailed previously.49Another important SCORE finding is that there is a great deal more variability in village-level responses to MDA than expected. Whether MDA is given using CWT or SBT, and whether given biannually, annually, or biennially, prevalence and intensity decline nicely in some villages, but not in others. Some villages may even have increased prevalence and, to a lesser degree, intensity, in the face of multiple MDAs. The SCORE program has termed these villages with poor response to multiple rounds of MDA as “persistent hotspots” (PHS). Additional SCORE evaluations of this issue are discussed in another article in this supplement49 others also focused on their occurrence in other large studies. This has led to an appreciation that PHS are real and need to be addressed in some way if programs are ever going to truly control or eventually eliminate schistosomiasis. The question of early identification of PHS and what to do when they are identified is now playing a role in WHO’s efforts to develop new guidelines for the control and elimination of schistosomiasis.In October 2015, SCORE held an ad hoc meeting, scheduled between the 2015 Coalition for Operational Research on Neglected Tropical Diseases meeting and the American Society for Tropical Medicine and Hygiene meeting in Philadelphia, to discuss potential next steps in defining and understanding this variability in communities to MDA. The meeting was attended either in person or by Skype by 12 SCORE investigators and included a WHO representative. The discussion was wide-ranging, including what to call these areas of concern, how they should be defined, what was causing them, and what research might be conducted to better understand them. Once SCORE’s data exposed the existence of PHS in the face of well-conducted MDA studies and the subsequent publication of articles on this topic,50 Nevertheless, by the time that SCORE began, consideration of snail control as a means of controlling schistosomiasis had gone out of practice. However, as elimination appeared to be within reach and has become a larger focus, all tools available to suppress transmission and stop infection needed to be considered as part of the armamentarium, and snail control became an essential part of SCORE’s Zanzibar and Seasonal Elimination Studies.At one time, snail control was the major means of schistosomiasis control. In several places, it had been demonstrated that it could be successful if consistently applied.Because the best snail control methods and approaches to monitoring were unclear, SCORE held a meeting in 2013 to discuss potential ways to control snails, including environmental, biologic, and chemical. Among the possibilities discussed were use of various snail predators or competitors, physical or herbicide-mediated habitat modifications, and molluscicides. Although many promising ideas were generated, none except the use of niclosamide was field ready, so all SCORE studies involving snail control used this chemical. A side benefit has been the training of individuals in Zanzibar and Côte d’Ivoire on how to apply niclosamide and monitor impact.51 which synthesized the literature, again showing that when done properly, snail control impacts transmission. Some of the findings and contributions of snail control in the SCORE studies are provided in another article in this supplement.29 Modeling work by SCORE also emphasized the value of snail control in elimination efforts.52In addition, SCORE published an RAP on snail control,53Both in relation to the increased emphasis on elimination of schistosomiasis, and potentially in relation to address PHS, WHO has recently initiated a renewed effort related to snail control and has published an updated manual on snail control and held two workshops on it in sub-Saharan Africa.A broad interchange and advocacy role was embedded in SCORE’s third objective: to provide evidence-based findings to assist in the development of new guidelines and assistance to NTD program managers. As described in the section about the creation of SCORE, a critical aspect of SCORE was the fostering of a community committed to control and elimination of schistosomiasis, integration of research and programs at the country level, and extensive involvement with WHO.The SCORE annual meetings, held at UGA every year starting in 2011, provided a forum for very frank and open discussions among the Secretariat, the principal investigators of the multiple sub-awards or their designees, program managers, representatives from the BMGF, WHO, and the Advisory Committee, along with occasional others from outside SCORE, about their progress or the lack thereof, and challenges as well as successes.Secretariat members or representatives from among the funded projects also attended all the COR-NTD annual meetings, multiple NTD NGO Network (NNN) meetings, AFRO’s NTD program managers’ meetings, and a variety of meetings at the WHO/NTD headquarters. Of critical importance was the SCORE team reporting into the WHO NTD Strategic and Technical Advisory Group (STAG) Monitoring and Evaluations working group, where data were discussed and if appropriate, passed to the STAG for adoption into WHO recommendations and programs. These meetings provided an opportunity to share SCORE’s findings with a much wider audience of those involved in NTD control and elimination and to get input from those working similarly on other NTD diseases. SCORE was also fortunate to be granted a symposium in each of the last 10 American Society of Tropical Medicine and Hygiene annual meetings, which provided a broader stage for discussing SCORE’s projects, challenges, and findings and getting input on important issues such as PHS. To help ensure that the findings from SCORE research are quickly adopted by organizations that are funding or implementing schistosomiasis control efforts, SCORE has involved WHO at every step and has involved itself with a variety of expert committees.During the course of SCORE, several changes occurred at the BMGF that affected direction and implementation, including the increased emphasis on elimination and the standardizing analyses in the gaining and sustaining and elimination studies.1Much has been learned from the SCORE studies and other work conducted during the years of SCORE. For example, SCORE studies reinforced the notion that MDA is a critical tool for decreasing prevalence of high-intensity infections and reducing morbidity. However, SCORE studies also make it clear that new approaches will be needed. It is clear that some of the contributions from SCORE in terms of PHS, snail control, and more sensitive assays will be critical to the way forward. The SCORE datasets, schistosome genetic sequences, and specimens in SCAN should be useful for years to come.1The end of SCORE is coinciding with the formulation of new WHO guidelines on schistosomiasis, and now both control and elimination are on the docket. One of the key insights from SCORE has been that, although the strategy for control of schistosomiasis was predicated on the strategy for the control of lymphatic filariasis (LF), schistosomiasis is not LF. Lymphatic filariasis control and elimination is based on annual MDA for 5 or 6 years to kill microfilariae (the infectious stage), and it then takes up to a year before their production resumes. Therefore, treatment stops continued transmission for up to a year. With schistosomiasis, someone can be infected immediately after treatment if they go into water inhabited by infected snails, and they can infect snails within 1–2 months of infection. Thus, the risk of infection and of infected people contributing to transmission is cumulative between annual MDAs. The SCORE data on PHS and trajectories of village responses to MDA emphasize the need for new approaches to monitoring and control in PHS and will be critical in formulating new guidelines. Another article in this supplement will discuss, in more detail, the thoughts of the SCORE secretariat and sub-awardees on the way forward beyond SCORE.54 Will drug resistance develop, putting us back into the 1970s with no role for preventive chemotherapy?55 These are issues that will need to be and will be dealt with beyond SCORE. With the support of the BMGF, many other organizations and agencies, and many other individuals, SCORE has had a good run and has, we believe, produced positive findings that are already helping shape the future of schistosomiasis control and elimination.Clearly, there are other critical issues related to schistosomiasis that were not addressed by SCORE, such as female genital schistosomiasis, how to treat those younger than 5 years, and what mapping/monitoring/impact assessment strategies will be both effective in determining PHS and realistic in terms of what an NTD program manager can actually do. Is it possible to confirm elimination and how do you detect early recrudescence? Will there be an effective vaccine by the time it is needed?


In northern Nigeria, UNICEF has supported introduction of a short message service (SMS) system for data transmission in the Community-based Management of Acute Malnutrition (CMAM) programme. The SMS system operates in parallel to the traditional paper-based system, and weekly data are transmitted directly from the health facilities to the federal level. For the paper system, monthly data summaries are passed through all levels of government. We assessed the data quality and performance of both CMAM information systems.We undertook a contextualised study in one state in north-west Nigeria, with additional analysis of secondary data from five states. Fieldwork methods included: observation of the data system in nine selected facilities in three local government areas; recounting of data for admissions, exits, and ready-to-use therapeutic food (RUTF) utilisation; and interviews with health workers and government officials.While the small number of facilities does not enable robust generalisation of the quantitative findings, the strengths and weaknesses detected pertain to the whole programme, as they relate to how the system was designed and is operated. We found that the accuracy and reliability of CMAM data were deficient to a similar extent in the paper-based and SMS systems. For the audited month, we found large discrepancies between recounted data and paper records in regard to admissions, exits and RUTF cartons consumed in the majority of facilities visited. There was also a large discrepancy in the reported percentage of “deaths or defaulters” (6.5%) compared to 22% based on a recount of outpatient cards. Errors are mainly introduced during data collection and when completing tallies at facility level.Our findings indicate the need for improvements in the design of the monitoring system, training and supervision of data management, and communication of results; as well as clear evidence on how measures to improve data quality may affect performance of individual CMAM clinics. The CMAM default and death rates currently reported in Nigeria are likely to be under-estimates, and therefore provide a misleadingly good impression of CMAM programme performance.The online version contains supplementary material available at 10.1186/s40795-020-00405-z. Each year in Nigeria, more than two and a half million children under age five are affected by severe acute malnutrition (SAM), or extremely low weight-for-height (wasting), a condition that if untreated would lead to nearly half a million deaths . There iProgrammatic approaches to treatment of severe acute malnutrition (SAM) in children are centred on provision of nutrition-dense foods to promote weight gain, alongside parental counselling on infant care and feeding. Over the past two decades, the advent of ready to use therapeutic foods (RUTF) has enabled a shift from in-patient to out-patient treatment of SAM . This apCMAM was introduced in northern Nigeria in 2009, supported by development partners such as UNICEF, Save the Children, Médecins Sans Frontières and Action Against Hunger. These partners work closely with the federal and state governments to provide CMAM services within the public health system in targeted facilities. Funding from the Children’s Investment Fund Foundation (CIFF), the UK Department for International Development and the European Union have more recently supported efforts to scale up CMAM services . Now theIn Nigeria, malnourished children admitted to the CMAM programme are treated weekly at outpatient clinics, with only the most severe cases admitted for inpatient care. At each visit, the child’s nutrition status is monitored, the carer is counselled, and the child is provided with essential drugs, vitamin A supplementation, vaccination (if required) and sufficient RUTF to last until the following visit . Mid-uppUntil 2016, the Nigeria CMAM programme used a paper-based system for data management, to support programme planning and monitoring. Since 2016, UNICEF supported the government of Nigeria to introduce an additional smartphone-based system with the aim to improve the standardisation, transfer and speed of reporting of monitoring information using Short Messages Service (SMS), based on the open source RapidPro platform . At the Figure With respect to the information flow back down between levels, in addition to transfer of the RapidPro datafile from federal to state level  undertook an assessment of the quality and use of CMAM routine monitoring data and of the performance of the underlying paper-based and SMS systems. The objective was to support improvements to the CMAM programme. The assessment was undertaken in the North-West of the country, in collaboration with UNICEF and with funding support from CIFF. Earlier coverage surveys undertaken in 2013/2014 in various states have highlighted problems with the quality of the CMAM programme data –16. For Data of good quality are needed to inform decision-making during programme monitoring, review, planning, and improvement; advocacy; and policy development and review . This stFigure We selected nine health facilities in three LGAs, in one northern Nigerian state. The number of facilities included was constrained by budgetary considerations. Nine facilities provided a range of size, performance, and peri-urban versus rural location, as shown in Table We adopted a mixed-methods approach for primary data collection  because a key goal was to identify potential means for system improvement. A large-scale solely quantitative study may have better revealed the extent and distribution of data quality problems, but a shallower understanding of their origins. We used a combination of tools and analytical approaches to explore the components of data quality depicted in the conceptual framework  for both the paper and SMS-based data systems. This paper describes the findings from the quantitative verification. Data use and constraints to usage were also assessed but are not covered in this article.Desk-based review of data collection and transmission forms and documentation ;Observation of the inputs and processes relating to the monitoring system in health facilities and semi-structured key-informant interviews with health workers and government officials at facility, LGA, state and federal level; observations and interviews were collated and synthesised according to the items in the conceptual framework. The interview guide  was developed for the study in part by adapting PRISM tools developed by the Measure Evaluation Project .Recount of data from the OTP (Outpatient Therapeutic Programme) cards for admissions, exits, and records for RUTF utilisation at these facilities for a specified time window in 2017;Primary data collection (November–December 2017) in nine facilities.Descriptive analysis of facility-level data from the paper-based and the SMS system provided by UNICEF for the period of January 2017 to July 2017 from five states, to examine completeness, aspects of reliability and accuracy in terms of internal consistency checks, outliers and trends to examine consistency between performance variables, as well as timeliness.Descriptive analysis to compare facility-level counts of admissions, exits and RUTF extracted from the paper-based and SMS-based monitoring systems against data recounted from source forms in the subset of facilities visited during fieldwork.The data sources and study methods included:Fuller details on methods are available from an alternative source . This paWe compared recounts of data from OTP cards performed during our visits to facilities, with data from the paper records held by the facilities for July 2017.Figure Figure We also intended to recount exits by the same exit categories used on the tally forms . However, this task was not straightforward due to gaps in data recorded in the “outcome” cell on the OTP cards. Hence where outcome data were missing, we used relevant data from elsewhere in the card to identify the most likely exit category. We combined defaulters and deaths, because without a functioning system of follow-up after discharge it is impossible to know if a defaulted beneficiary is alive and thus a ‘true’ defaulter, or if they have died. The verification suggested a considerably higher number of defaulters or deaths than were reported in the electronic databases. For July 2017, the reported percentage of “deaths or defaulters” was 29 children or 6.5% of all exits reported through the CMAM system, compared to 72 children or 22% based on the recount of OTP cards.Figure Where discrepancies existed for admissions, total exits and RUTF consumption, the reported values tended to be higher than the recounted values  is affected by severe resource constraints. Due to this there is inadequate provision of forms, electricity and storage; and inadequate human resources, high workloads and capacity issues. An NFP commented “Secondly, although CMAM trainings were reported to include sessions on how to complete forms and tally data; there is a lack of clear printed guidelines, training materials and protocols on CMAM data capture for health-workers. The national CMAM guidelines were not at hand in any of the facilities visited; and in any case do not include details on data tallying, protocols for storing paper records, or the new SMS system. Also, we observed that various versions of forms for recording data are being used.Observations and interviews indicate two main underlying explanations for the inconsistencies between CMAM operations and national guidelines, which affect accuracy and reliability of the CMAM data:We compared the weekly tallies collected at health facilities  and exits (12 and 2%) for two facilities. The values entered at LGA level carried over into the paper-based datafile indicating data transfer between facility and LGA level as a potential source of inaccuracy in the electronic data.The analysis found very few errors in data entry at state level: The state-level electronic datafile matched the LGA paper-based data for exits and admissions in all but one instance.The discrepancies observed between the LGA reports and weekly tallies could be due to introduction of errors when the NFP copied data between paper forms. Alternatively, errors may have been introduced when the facility-in-charge copied data from the paper form stored at the facility (viewed by the study team) and the paper form they later submitted to the NFP. Both factors could plausibly contribute to the discrepancies, since our observations indicated a lack of formal quality assurance procedure for data transfer between levels.n=299 facility-months). The datasets should be consistent since they are both derived from the same paper records  held at the facilities. For those 46 facilities for which information was available, Table We compared the electronic datafiles from the paper-based and SMS systems for all records between January and July 2017  are the same. A potential source of discrepancies is errors introduced during data entry to mobile phones. Although no such errors were observed during the study, the study team visited only nine facilities, and the presence of observers may have positively affected conduct of the data entry to mobile phones on those few occasions, while the data in Table For the paper-based system, all facilities reported on a monthly basis throughout the reference period, so reporting was complete in terms of months with valid observations. In contrast, completeness of the SMS dataset was deficient with respect to weeks with valid observations. We found that, on average, 7% of weekly reports were missing  were missing for only 0.1% of weekly reports, and RUTF stock reported at the beginning of the week was missing for 5.9% of weekly reports. For the paper dataset, the numbers of children in treatment at beginning and end of month were missing for 11 and 12% of monthly reports respectively.The timeliness of the SMS data was weak. We assessed this using the indicators produced within the UNICEF dashboard, which allows facilities to report until the Monday following the OTP day. Figure The missing values and inconsistencies noted during secondary data analysis appeared to be affected by the absence of a formal process to verify the numbers of children in the programme, based on child-level records. A key challenge was that staff carry over the number of “children in treatment” from the end of the previous week to the start of the new week, rather than by counting OTP cards. The practice of carrying over data is also used for the paper dataset (data are carried over from the end of previous month). The variable “number of children in treatment” is used to calculate requirements for RUTF, so this is a potential incentive for maintaining inflated values in the dataset.I’m expected to send the SMS report the same day as the CMAM clinic, but can’t always do this because of the phone network. Last week I couldn’t send it until Friday, and so contacted X who said it was a problem for everyone, and that I should just keep trying.”“With respect to the relatively poor timeliness of weekly report submission and incompleteness of the resultant SMS dataset revealed by our secondary data analysis, the coverage and reliability of the mobile phone network was perceived to be the major challenge. For example, one recently appointed CMAM-in-charge  said.While most of Nigeria has good network coverage, there are pockets where coverage is lacking, and also network quality varies across time and space. Another factor may be low motivation to submit the texts. While study interviews revealed health-workers’ high motivation to submit their data on time, and frustration when this was not possible, these sentiments may not be ubiquitous. The paper-based CMAM monitoring is part of the formal governmental reporting system, while the parallel SMS-based monitoring may be considered less important as it is not owned by the health system.For our assessment of the SMS and paper-based CMAM monitoring systems in northern Nigeria, we have summarised the major findings relating to accuracy, reliability, completeness and timeliness. The study’s primary data collection is based on a subset of purposively selected facilities and the findings can therefore not be generalised to the wider CMAM programme in terms of the values of indicators calculated. However, we deliberately chose to undertake a small-scale contextualised study in a single state, and used mixed qualitative and quantitative methods, because we needed to understand the origins of any identified gaps in data quality. We analysed the full system including inputs and processes, and hence contend that strengths, weaknesses and patterns detected are very likely to be found across the CMAM programme, as they relate to the way the system was designed and is operated, in the facilities where observations took place and elsewhere. In this section, we discuss the implications of the most salient findings to the CMAM programme in Nigeria and more widely.We found discrepancies between recounted and reported data for admissions, total exits, defaults and deaths, and RUTF consumption. It is not possible to distinguish between loss/removal of OTP cards and errors during data tallying as explanatory factors, but the large size of discrepancies for some facilities indicate loss or discarding of cards as the major factor at least for those facilities. This highlights the importance of developing quality assurance processes for the tallying procedure, as well as guidance on the storage of paper records. Without improvement of storage practices, attempts to audit data quality will remain a challenge.The discrepancies in the reported and recounted “death or default” rates highlight several concerns. Firstly, although international guidelines state that children should be followed up periodically after discharge , this doSecondly, our data point to artificially low death and/or default rates associated with the CMAM programme in Nigeria. The explanatory factors relate mainly to discrepancies between actual treatment practices and national CMAM guidelines . AlthougOur findings highlight the importance of instigating a system to identify defaulters through examination of OTP cards, as part of a quality assurance process of the weekly tallying procedure. With respect to deaths, since for many facilities it is currently impossible to record an accurate measure, it seems logical to propose dropping the indicator of mortality from the data recording process. However, death is a valuable outcome measure, so it would be preferable to work towards strengthening the community-based component of the programme, and meanwhile instigate a system whereby the indicator is flagged as unreliable for those CMAM facilities without community volunteers.The importance of these proposals relates to the common use of death, defaulting and recovery rates as indicators of the effectiveness of CMAM programmes, as defined by Sphere Standard 2.2 relating to management of SAM . This stWe noted that data recorded for the variable “children in treatment” for the beginning of each period (week/month) are carried over from the end of the previous period (week/month). We suggest that recording of number of children in the programme should be verified each week based on child-level records and be reported through the information system. This would enable cross-checks of amount of RUTF distributed against number of children attending, and identification of facilities for closer scrutiny.This suggestion is not made lightly, since any increase in data collection and reporting requirements would be an additional burden to staff who are already over-worked. Also, it requires a change to the current approach and a protocol would have to be developed and tested. But because inaccuracies in the indicator affect allocation of RUTF, it is important to tackle this issue.There are several advantages of the SMS reporting system over the paper-based system. The most obvious are the fewer intermediate data transfer and processing steps (which increase the risk of introducing errors in the data), and that it is not necessary to physically transport records. In the SMS system, data reach the federal level faster, which facilitates more rapid programme decision-making, even considering the study findings on delays in submission of data. Interviews revealed that RUTF stock alerts are transmitted automatically when low levels of stock are detected within the dataset. There is also a reduced risk of data loss that may arise from loss or destruction of paper forms.The drawbacks of the SMS system are that sending the texts adds an extra task to the health-workers’ workload, that the completeness and timeliness of the dataset is dependent on network coverage, and that the system is not institutionalised. Remote facilities are particularly affected by poor network coverage, which can delay transmission of the data. Further, if the SMS system were to operate without the paper-system in parallel, the LGA and state levels would be less aware of data reported by facilities under their supervision. This brings the associated risk of reducing quality assurance mechanisms at those levels, as well as motivation to use the data.We construe that in the current circumstances, it is not possible to phase out the paper-based system for transferring data. This would require a more reliable network coverage, and a means of sharing the SMS system findings with LGA and facility level staff. The latter might be done via paper reports, or a “real-time” report that could be accessed on mobile phones (in addition to the existing practice of discussing the data at state-level meetings). Another action that would likely improve motivation and thereby data quality is institutionalisation of the monitoring system, by inclusion of the nutrition indicators in the routine health information system.This study identified that implementation of a mobile technology for CMAM data transfer in Nigeria benefits the programme by providing rapid electronic notification of stock shortages. However, mobile network coverage is not sufficiently reliable for the SMS system to replace the paper-based system. Several of our findings concur with those of earlier studies which indicated that national protocols for admissions, and definitions of defaulting and recovery, were not being applied; and that outcome indicators and counts of children admitted were inaccurate –16. ThesThe study highlights the need for more comprehensive training, supervision and quality assurance focused on the correct completion of OTP forms, weekly tallying and data transfer. A crucial step is recognition and acceptance that if data quality improves, performance indicators may get worse. Temporary deterioration in performance indicators can be a positive sign of better data processes and reporting, rather than a sign of a decline in performance.Additional file 1. CMAM Interview and verification instruments. Facility-level data collection tools; LGA-level data collection tools; State-level data collection tools; Federal-level data collection tools; Protocol for verification of CMAM admission and discharge data; OTP data verification collection forms, and RUTF data verification collection forms.


The link between psoriasis and sport is a controversial issue. The topic has been poorly investigated, and nowadays there are many unsolved questions, dealing with the role of psoriasis in influencing the sporting habits of patients and, vice versa, the impact of sport activity on course, severity and extent of the disease, with particular regard to the indirect benefits on cardiovascular risk and metabolic syndrome. Moreover, the role of physical activity on patients’ quality of life and the potential limitations on physical activity due to joint involvement have not been well elucidated until now. In this narrative review we will try to provide answers to these queries. Psoriasis (Pso) is a chronic inflammatory immune-mediated skin disease with an estimated worldwide prevalence of approximately 2–3% . For a lhttps://ncbi.nlm.nih.gov/PubMed accessed on 30 December 2020), using the keys related to psoriasis and sport. The search string used was “psoriasis”[All Fields] AND  with BMI ≥ 25 kg/m2 perceived themselves as overweight. Skin involvement was considered a limit to perform sport, leading to complete abandonment of any physical activities, emphasizing the cosmetic aspect of the disease. This in spite of the positive influence of sport on Pso severity. Greater benefits were reported from activities such as cycling and walking compared to endurance sports, and even more so if compared to home chores. Furthermore, it was noted that patients with moderate or severe psoriasis were more sensitive to positive or negative feedback from the doctor about food and sports habits. Among the conclusions of the study, it is suggested that the optimal pathology control could facilitate weight loss through physical activity [Schwarz et al. conducted a study, called ERAPSO, on a population of 9940 german patients affected by both Pso and overweight. Most of them had attempted an approach to weight loss through diet and sports. About 20% were exercising during the study in order to lose weight. Patients with a BMI greater than 25 kg/mIn another study, Frankel et al. investigated motor activity habits in US nurses diagnosed with psoriasis through questionnaires specifically administered to evaluate the correlation between vigorous exercise and risk of developing Pso. They found an inverse relationship between the two aspects. Although not all grades of physical activity /hour per week) have shown statistically significant results, the benefits resulting from vigorous exercise seem to suggest a threshold effect. Furthermore, the variable “amount of exercise” appeared independently related to the risk of developing psoriasis with respect to the BMI level of the patients. The “vigorous” activity was set as 105′/week of running or 180′/week of swimming/tennis, while mere walking did not produce positive or negative implications for the disease activity. Only certain aerobic activities, such as running, have proven useful in preventing psoriasis. It may be due to the fact that other sports activities with similar energy expense showed a discontinuous level of intensity. Moreover, it was very rare to observe patients engaged in a single high intensity activity for prolonged periods of time rather than various activities with variable intensity and shorter periods of time. Two main hypotheses have been proposed to explain such results: modification of the cytokine profile from a pro-inflammatory to a less pro-inflammatory subset  and reduction of psycho-emotional stress which, through a modulation of the activity of T lymphocytes, would regulate the disease’s activity. A possible limitation to the study could be represented by the confounding element of the beneficial action of the sun carried out by ultraviolet (UV) rays; however, patients who spent the same amount of energy walking outdoors compared to those who did vigorous activity outdoors reported significantly less marked results [Do et al. researched the link between the extent of psoriatic lesions and the likelihood of participating in leisure-time moderate to vigorous physical activity (MVPA). The MET-minutes spent during MVPA among the patients was also evaluated. They found out that, even though the difference in the last 30 days of the time doing sports was not statistically significant between the two groups, the METs consumed per minute were 30% less in the psoriatic group. This finding was attributed, by the authors, to the fact that patients with more extensive skin lesions are less prone in engaging physical activity .In the large study of Balato et al. the relationship between sport and Pso was investigated comparing 416 sportsmen, 489 controls and 400 psoriatic patients (sex- and age-matched). The authors noted that although there was a similar percentage of family history of psoriasis among sportsmen and controls, the prevalence of the disease was significantly lower in the sportsmen group. Only 1.7% of sportspeople had Pso compared to 5.4% of controls. The number of subjects who actively played sports was much less among the Pso patients than the controls, suggesting that Pso may be a limitation to physical activity. Among psoriatic patients, a significant number of them (95) practiced sports before the disease onset. The Authors suggest that physical activity would exert positive effects on Pso not only through a simple mechanism of weight loss but also at a molecular level, inducing epigenetic modifications (DNA methylation and histone acetylation) and decreasing pro-inflammatory cytokines  and leptin. The main limitations of this study are that the administered questionnaires were doctor specific and not based on those normally used  and that, to better define the link between sport and Pso, a larger sample of the population would be requested [Megna et al. compared second-league footballers and healthy controls with overlapping physical characteristics  and similar family history for psoriasis by means of a questionnaire. It emerged that players affected by psoriasis did not perceive sport as a factor negatively influencing the natural history of their disease. A higher prevalence of psoriasis was found in controls who did not perform any physical activity with respect to those regularly involved in exercise programs, suggesting that physical activity may play a protective role against the development of cutaneous manifestations of the disease as well as its cardio-metabolic comorbidities .A relevant question about the possible side effects of sport in case of psoriatic disease was posed by Brophy et al. In a case report, they describe the case of a 39-year-old athlete who, presenting with recurrent monolateral knee effusions, received a late diagnosis of psoriatic arthritis since his injuries were initially diagnosed as due to trauma while playing; in addition, the patient had a positive family history of seronegative and non-seronegative spondyloarthritis. Following a suitable treatment, the patient not just recovered the complete function of his knee, but also noticed improvements in other joints which previously had not prevented him from attending competitive sports. As the Authors say, a patient suffering from oligoarticular forms of psoriatic arthritis not only would benefit from an early and aggressive treatment, but also should be aware of an intrinsic structural weakness of his own cartilages, and therefore limit the use of the joints in sports like the contact ones. We see, therefore, how sport presents itself both as a potential target for the treatment of psoriatic disease and, on the other hand, as a source of possible injury .A similar event was reported by Corn et al., concerning a patient known for a history of psoriasis who had seen the appearance of characteristic lesions on the soles of the feet following sports, seeing how the Koebner phenomenon could, therefore, be a spy of a pathology otherwise with minimal clinical manifestations .Psoriasis can have several comorbidities linked to it, mostly dismetabolic ones caused by lack of exercise. One of the main means to evaluate a patient’s fitness is through examination of the cardiorespiratory fitness (CRF) The link between CRF and the severity of psoriasis was highlighted by Wilson et al. In this study, important results and questions emerge regarding the role of physiological processes that occur during exercise (sweating and heat dissipation) in relation to psoriatic plaques. Fitness measurement was performed by running tests on the treadmill. The results demonstrated a significant decrease in cardiorespiratory fitness in psoriatic patients compared to healthy controls, suggesting other mechanisms besides the lack of constant training. According to the Authors the disease activity, measured through the PASI index, can also be related to heart rate, demonstrating a correlation between psoriasis and cardio-metabolic risk. It should be noted that cardiorespiratory fitness was not investigated in this study through maximal exercises that could better identify differences between the groups. Moreover, the cohort of partecipants is too small to clearly demonstrate the association between disease severity and CRF lowering. However, this study offers interesting research ideas regarding factors potentially related to psoriatic disease and their role in decreasing CRF in such patients .In another study, Wilson proposed a specific questionnaire  to know what kind of activities the psoriatic patient engage in order to lose weight. The study population included 9174 participants, of which 232 had psoriasis. The results showed that only 48% of the Pso patients tried to lose weight through physical activity, compared to the 62.4% of healthy subjects. Moreover, just 16.1% of Pso patients performed vigorous physical activity, compared to 28% of unaffected participants. It is the author’s opinion that patients affected by both psoriasis and obesity might practice sport less than patients affected by just one of these conditions. A better dialog between physician and patients could help them to find new ways of doing sports in order to lose weight .On the same note, Naldi et al. conducted a study aimed at finding a correlation between psoriasis and its improvement through diet and physical excercise. In this trial, 303 overweight-obese patients were enrolled, and it was proposed to them either a 15 min meeting in which they were instructed what kind of behaviours they should have adopted in order to lose weight or a full dietary/physical programme, managed by a physician. We believe that this study, even though claims overall significant results, presents several limitations: the patients treated with systemic drug were all put together without any further selection criterion ; a closer supervision in the interventional arm could have produced intrinsically better results; this study was conducted in a short period of time, without a proper follow-up to assess the maintenance of this loss of weight through time. Overall, this study, once again, tells us how much it is important for a complete medical team to follow through the years psoriatic patients in order to achieve complete control over this disease .The studies cited so far are mainly based on the relationship between sport and psoriasis; it must be said, however, that even simple weight loss could be a sufficient factor to determine a clinical improvement. In a large study, Kim et al. showed that the metabolic syndrome features and Pso lesions are directly related . MoreoveJensen et al. have conducted a study on long-term efficacy of weight loss in Pso patients. Even though in this case the element “sport activity” has not been taken into consideration for weight loss purposes, it is undeniable that slimming is a complex process able to exert, if supported by regular sporting activity, improvement of PASI and DLQI . As reviOut of all the possible alimentary regimens, the mediterrean diet seems to be the one less linked to severe forms of psoriasis, thus suggesting its protective role in the progression of this disease . The pooFinally, another study by Ferguson et al. suggests a role of central adiposity in the development of psoriasis, psoriatic arthritis and rheumatoid arthritis: all of these conditions were significantly associated with overweight and lack of physical activity, even after correction of the BMI, thus suggesting that the weight could be somehow linked to the development of several autoimmune diseases .It is well-known that psoriasis has a strong impact on patients’ life. It influences working habits, poses a significant financial burden, but most of all, dramatically impairs their quality of life and psychological status. The visibility of the disease is a deterrent for the practice of some sports, especially for those requiring the exposure of large parts of the body. This has been well documented in the study of Ramsay et al., in which 72% of patients declared to consciously avoid swimming, a percentage that went down to a still consistent 46% even in the case of mild psoriasis. Similarly, 64% of patients avoided bath and showers in public. Pso also influenced other aspects linked to sport activity like the choice of color and types of clothing (in particular summer clothes). Over half of the patients reported the sensation that their medical condition could represent a social stigma, as they are perceived to be contagious, causing social phobia and refraining from activities outside the house. Furthermore, asking the patients what the worst factors of the disease were, they replied for about 80% that one’s appearance, linked to the disease and the itch, represented a major limit to carry out some types of sport. This observation could suggest that, if these patients have had pleasure in practicing contact sports, psoriasis would prove to be an insurmountable psychological obstacle regardless of the severity of the disease .On a group of patients 223) ranged 18 to 83 years of age, Nyunt et al. used the classic DLQI to assess the impact on the quality of life by psoriasis. Factors significantly associated with scarce quality of life included sports, PASI, marital status, level of work or study, nail dystrophy, visible affected areas, itching, sleep quality, stress and infections. The Authors suggest that Pso would invalidate sports activity for psychological and social reasons (shame of one’s own body) or for the exposure to repeated physical trauma as important stimulus for the appearance of Koebner phenomenon. The main limits of this study are the scarce variety of cases, since it was conducted in a tertiary medical center of and the pool of individuals was composed of patients with severe psoriasis. Furthermore, the calculation of BSA and PASI of skin lesions was carried out without taking precise measurements but “at a glance” [ ranged 1About the relevance of the research items of the DLQI questionnaire, Rencz et al. observed that some of these, such as sport (28.4%) and others , are considered as irrelevant, especially by a portion of the population made up of elderly patients/female patients/scarcely educated patients. The Authors suggest reconsidering the period of time for evaluating the questionnaire in order to highlight aspects previously considered unnecessary by patients. The conclusion of the study is controversial since, if on one hand increasing the observational period (one week currently) would increase the relevance of the item, this would require at the same time a greater memory effort. The Authors conclude that, however, the DLQI is a valid and necessary tool for defining the quality of life of Pso patients, in relation to the increase in average age .Barbieri et al. investigated the impact of socioeconomic factors on “not relevant” responses (NRRs) on the DLQI. They found that the items regarding sport, sexual difficulties and work/study had the greatest frequency of NRRs, especially in unemployed people or on the basis of marital status. The Authors concluded that differences of socioeconomic status may cause underestimation of disease burden and treatment disparities among certain sociodemographic groups .Duvetorp et al., again by meaning of DLQI, conducted a research on the people of Sweden, Denmark and Norway noting that psoriasis alone did not have a strong impact on patients’ daily lives with regards to sports (14.5%); even if combined with psoriatic arthritis this value rose to 44% .In a 2002 study by Mork et al. the authors tested the effectiveness of a variant of the classic DLQI called DLQI-N, in 230 Noerwegian Pso patients. The Authors noted that for 3 items of this questionnaire  most patients considered these as “not relevant”: this, again according to the Authors, could be due to the fact that the responses “not relevant” and “no impact of the disease” on the activities in question were interpreted in the same way .Van Geel et al. compared the questionnaire for adults (DLQI) and minors . Patients aged between 16 and 17 were sampled and both questionnaires were administered. These authors noticed a big difference between the scores concerning the “sport” item if investigated through the DLQI or the C-DLQI. The discrepancy between the two scores is believed to be due to the different definition of the item where, by adding the word “swimming” in the C-DLQI, the patients obtained a higher score. This could reflect that swimming plays an important role in adolescence not only in a competitive setting but also in other aspects of social life such as summer holidays. This study highlights, once again, the importance of the cosmetic aspect of psoriasis .Leino et al. administered a specific questionnaire of 11 dichotomous categories, inserting sports and non-sports activities, to evaluate the impact of psoriasis in leisure activities. They observed that the majority of people reduced (23.7%) or completely abandoned 30.2%) sport activities because of psoriasis, with differences between sexes. While females tend to reduce sport activity, males showed a dichotomous behaviour, with complete abandonment or insignificant reduction. This may be due, according to the Authors, to the fact that males carried out these activities with greater intensity before the onset of the disease. Another important fact is that the average age of patients who decreased or abandoned sport was significantly lower than those who did not decrease it . The rol.2% sportIn contrast with the studies so far examined, Demirel et al. suggested that mild and moderate psoriasis does not actually influence the daily physical activity of the patients: in fact, in their experience, Pso patients tend to do more physical exercise .Eghlileb et al. tested the quality of life of relatives and partners of psoriatic patients. Just 8% of the subjects examined referred no impact on their quality of life depending on the disease of close Pso patients. In particular, 44% of the interviewees reported difficulties in playing sports together with relatives or partners because of the disease. To justify these limitations, elements such as hospital treatment and the embarrassment of exposing the skin in public have been brought into consideration . These results suggest an important role of the stress experienced by people alongside patients not only as a consequence of the disease but as a further reason for the aggravation of the psychological status of the patients, with possible repercussions also on the severity of the disease itself .In the study of Jenner et al. inherent to economic and social burden of PSO, over one third of the patients reported difficulties in performing sports activities. One of the possible explaination is the increase of the costs related to sport activities due to a more careful choice of clothing and their cleaning, to the more specific selection of less aggressive but more expensive detergents as well as to unmanageable expenses to carry out sports in constant manner .The analysis of the Literature strongly suggests a close mutual influence between sport and Pso, showing a correlation between the quantity and/or quality of sport activities and severity and course of the disease. Sport activity, through molecular mechanisms, can reduce the levels of the pro-inflammatory cytokines systemically ,8, with Psoriasis has an impact on many aspects of the daily life of the patients, and the role played by sport in the quality of life seems relevant even if underestimated. There is still much to investigate about the influence of different types of sport on Pso and psoriatic arthritis at both molecular and clinical levels. In particular, the relationship between physical activity and severity of Pso in patients with cardiovascular and/or metabolic comorbidities may be of help to better understand the mechanisms underlying different ways of presentation of a unique chronic inflammatory state. Sports may represent a striking non-pharmacological resource in complex patients like the psoriatic ones, especially within programs of education and promotion of a healthier lifestyle.