Female genital schistosomiasis burden and risk factors in two endemic areas in Malawi nested in the Morbidity Operational Research for Bilharziasis Implementation Decisions (MORBID) cross-sectional study.

BACKGROUND: Female genital schistosomiasis (FGS), caused by the parasite Schistosoma haematobium (Sh), is prevalent in Sub-Saharan Africa. FGS is associated with sexual dysfunction and reproductive morbidity, and increased prevalence of HIV and cervical precancerous lesions. Lack of approved guidelines for FGS screening and diagnosis hinder accurate disease burden estimation. This study evaluated FGS burden in two Sh-endemic areas in Southern Malawi by visual and molecular diagnostic methods. METHODOLOGY/PRINCIPAL FINDINGS: Women aged 15-65, sexually active, not menstruating, or pregnant, were enrolled from the MORBID study. A midwife completed a questionnaire, obtained cervicovaginal swab and lavage, and assessed FGS-associated genital lesions using hand-held colposcopy. 'Visual-FGS' was defined as specific genital lesions. 'Molecular-FGS' was defined as Sh DNA detected by real-time PCR from swabs. Microscopy detected urinary Sh egg-patent infection. In total, 950 women completed the questionnaire (median age 27, [IQR] 20-38). Visual-and molecular-FGS prevalence were 26·9% (260/967) and 8·2% (78/942), respectively. 6·5% of women with available genital and urinary samples (38/584) had egg-patent Sh infection. There was a positive significant association between molecular- and visual-FGS (AOR = 2·9, 95%CI 1·7-5·0). 'Molecular-FGS' was associated with egg-patent Sh infection (AOR = 7·5, 95% CI 3·27-17·2). Some villages had high 'molecular-FGS' prevalence, despite <10% prevalence of urinary Sh among school-age children. CONCLUSIONS/SIGNIFICANCE: Southern Malawi carries an under-recognized FGS burden. FGS was detectable in villages not eligible for schistosomiasis control strategies, potentially leaving girls and women untreated under current WHO guidelines. Validated field-deployable methods could be considered for new control strategies.

How well do coverage surveys and programmatically reported mass drug administration coverage match? Results from 214 mass drug administration campaigns in 15 countries, 2008-2017.

INTRODUCTION: Delivering preventive chemotherapy through mass drug administration (MDA) is a central approach in controlling or eliminating several neglected tropical diseases (NTDs). Treatment coverage, a primary indicator of MDA performance, can be measured through routinely reported programmatic data or population-based coverage evaluation surveys. Reported coverage is often the easiest and least expensive way to estimate coverage; however, it is prone to inaccuracies due to errors in data compilation and imprecise denominators, and in some cases measures treatments offered as opposed to treatments swallowed. OBJECTIVE: Analyses presented here aimed to understand (1) how often coverage calculated using routinely reported data and survey data would lead programme managers to make the same programmatic decisions; (2) the magnitude and direction of the difference between these two estimates, and (3) whether there is meaningful variation by region, age group or country. METHODS: We analysed and compared reported and surveyed treatment coverage data from 214 MDAs implemented between 2008 and 2017 in 15 countries in Africa, Asia and the Caribbean. Routinely reported treatment coverage was compiled using data reported by national NTD programmes to donors, either directly or via NTD implementing partners, following the implementation of a district-level MDA campaign; coverage was calculated by dividing the number of individuals treated by a population value, which is typically based on national census projections and occasionally community registers. Surveyed treatment coverage came from post-MDA community-based coverage evaluation surveys, which were conducted as per standardised WHO recommended methodology. RESULTS: Coverage estimates using routine reporting and surveys gave the same result in terms of whether the minimum coverage threshold was reached in 72% of the MDAs surveyed in the Africa region and in 52% in the Asia region. The reported coverage value was within ±10 percentage points of the surveyed coverage value in 58/124 of the surveyed MDAs in the Africa region and 19/77 in the Asia region. Concordance between routinely reported and surveyed coverage estimates was 64% for the total population and 72% for school-age children. The study data showed variation across countries in the number of surveys conducted as well as the frequency with which there was concordance between the two coverage estimates. CONCLUSIONS: Programme managers must grapple with making decisions based on imperfect information, balancing needs for accuracy with cost and available capacity. The study shows that for many of the MDAs surveyed, based on the concordance with respect to reaching the minimum coverage thresholds, the routinely reported data were accurate enough to make programmatic decisions. Where coverage surveys do show a need to improve accuracy of routinely reported results, NTD programme managers should use various tools and approaches to strengthen data quality in order to use data for decision-making to achieve NTD control and elimination goals.

Defining elimination as a public health problem for schistosomiasis control programmes: beyond prevalence of heavy-intensity infections.

WHO's 2021-30 road map for neglected tropical diseases (NTDs) outlines disease-specific and cross-cutting targets for the control, elimination, and eradication of NTDs in affected countries. For schistosomiasis, the criterion for elimination as a public health problem (EPHP) is defined as less than 1% prevalence of heavy-intensity infections (ie, ≥50 Schistosoma haematobium eggs per 10 mL of urine or ≥400 Schistosoma mansoni eggs per g of stool). However, we believe the evidence supporting this definition of EPHP is inadequate and the shifting distribution of schistosomiasis morbidity towards more subtle, rather than severe, morbidity in the face of large-scale control programmes requires guidelines to be adapted. In this Viewpoint, we outline the need for more accurate measures to develop a robust evidence-based monitoring and evaluation framework for schistosomiasis. Such a framework is crucial for achieving the goal of widespread EPHP of schistosomiasis and to meet the WHO road map targets. We encourage use of overall prevalence of schistosome infection (instead of the prevalence of heavy-intensity infections), development of species-dependent and age-dependent morbidity markers, and construction of a standardised monitoring and evaluation protocol.

Review of 2022 WHO guidelines on the control and elimination of schistosomiasis.

Schistosomiasis is a helminthiasis infecting approximately 250 million people worldwide. In 2001, the World Health Assembly (WHA) 54.19 resolution defined a new global strategy for control of schistosomiasis through preventive chemotherapy programmes. This resolution culminated in the 2006 WHO guidelines that recommended empirical treatment by mass drug administration with praziquantel, predominately to school-aged children in endemic settings at regular intervals. Since then, school-based and community-based preventive chemotherapy programmes have been scaled-up, reducing schistosomiasis-associated morbidity. Over the past 15 years, new scientific evidence-combined with a more ambitious goal of eliminating schistosomiasis and an increase in the global donated supply of praziquantel-has highlighted the need to update public health guidance worldwide. In February, 2022, WHO published new guidelines with six recommendations to update the global public health strategy against schistosomiasis, including expansion of preventive chemotherapy eligibility from the predominant group of school-aged children to all age groups (2 years and older), lowering the prevalence threshold for annual preventive chemotherapy, and increasing the frequency of treatment. This Review, written by the 2018-2022 Schistosomiasis Guidelines Development Group and its international partners, presents a summary of the new WHO guideline recommendations for schistosomiasis along with their historical context, supporting evidence, implications for public health implementation, and future research needs.

Effect of preventive chemotherapy with praziquantel on schistosomiasis among school-aged children in sub-Saharan Africa: a spatiotemporal modelling study.

BACKGROUND: Over the past 20 years, schistosomiasis control has been scaled up. Preventive chemotherapy with praziquantel is the main intervention. We aimed to assess the effect of preventive chemotherapy on schistosomiasis prevalence in sub-Saharan Africa, comparing 2000-10 with 2011-14 and 2015-19. METHODS: In this spatiotemporal modelling study, we analysed survey data from school-aged children (aged 5-14 years) in 44 countries across sub-Saharan Africa. The data were extracted from the Global Neglected Tropical Diseases database and augmented by 2018 and 2019 survey data obtained from disease control programmes. Bayesian geostatistical models were fitted to Schistosoma haematobium and Schistosoma mansoni survey data. The models included data on climatic predictors obtained from satellites and other open-source environmental databases and socioeconomic predictors obtained from various household surveys. Temporal changes in Schistosoma species prevalence were estimated by a categorical variable with values corresponding to the three time periods (2000-10, 2011-14, and 2015-19) during which preventive chemotherapy interventions were scaled up. FINDINGS: We identified 781 references with relevant geolocated schistosomiasis survey data for 2000-19. There were 19 166 unique survey locations for S haematobium and 23 861 for S mansoni, of which 77% (14 757 locations for S haematobium and 18 372 locations for S mansoni) corresponded to 2011-19. Schistosomiasis prevalence among school-aged children in sub-Saharan Africa decreased from 23·0% (95% Bayesian credible interval 22·1-24·1) in 2000-10 to 9·6% (9·1-10·2) in 2015-19, an overall reduction of 58·3%. The reduction of S haematobium was 67·9% (64·6-71·1) and that of S mansoni 53·6% (45·2-58·3) when comparing 2000-10 with 2015-19. INTERPRETATION: Our model-based estimates suggest that schistosomiasis prevalence in sub-Saharan Africa has decreased considerably, most likely explained by the scale-up of preventive chemotherapy. There is a need to consolidate gains in the control of schistosomiasis by means of preventive chemotherapy, coupled with other interventions to interrupt disease transmission. FUNDING: European Research Council and WHO.

Control and Elimination of Schistosomiasis as a Public Health Problem: Thresholds Fail to Differentiate Schistosomiasis Morbidity Prevalence in Children.

BACKGROUND: Current World Health Organization guidelines utilize prevalence of heavy-intensity infections (PHIs), that is, ≥50 eggs per 10 mL of urine for Schistosoma haematobium and ≥400 eggs per gram of stool for S. mansoni, to determine whether a targeted area has controlled schistosomiasis morbidity or eliminated schistosomiasis as a public health problem. The relationship between these PHI categories and morbidity is not well understood. METHODS: School-age participants enrolled in schistosomiasis monitoring and evaluation cohorts from 2003 to 2008 in Burkina Faso, Mali, Niger, Tanzania, Uganda, and Zambia were surveyed for infection and morbidity at baseline and after 1 and 2 rounds of preventive chemotherapy. Logistic regression was used to compare morbidity prevalence among participants based on their school's PHI category. RESULTS: Microhematuria levels were associated with the S. haematobium PHI categories at all 3 time points. For any other S. haematobium or S. mansoni morbidity that was measured, PHI categories did not differentiate morbidity prevalence levels consistently. CONCLUSIONS: These analyses suggest that current PHI categorizations do not differentiate the prevalence of standard morbidity markers. A reevaluation of the criteria for schistosomiasis control is warranted.

Urogenital schistosomiasis infection prevalence targets to determine elimination as a public health problem based on microhematuria prevalence in school-age children.

BACKGROUND: Recent research suggests that schistosomiasis targets for morbidity control and elimination as a public health problem could benefit from a reanalysis. These analyses would define evidence-based targets that control programs could use to confidently assert that they had controlled or eliminated schistosomiasis as a public health problem. We estimated how low Schistosoma haematobium infection levels diagnosed by urine filtration in school-age children should be decreased so that microhematuria prevalence was at, or below, a "background" level of morbidity. METHODOLOGY: Data obtained from school-age children in Burkina Faso, Mali, Niger, Tanzania, and Zambia who participated in schistosomiasis monitoring and evaluation cohorts were reanalyzed before and after initiation of preventive chemotherapy. Bayesian models estimated the infection level prevalence probabilities associated with microhematuria thresholds ≤10%, 13%, or 15%. PRINCIPAL FINDINGS: An infection prevalence of 5% could be a sensible target for urogenital schistosomiasis morbidity control in children as microhematuria prevalence was highly likely to be below 10% in all surveys. Targets of 8% and 11% infection prevalence were highly likely to result in microhematuria levels less than 13% and 15%, respectively. By contrast, measuring heavy-intensity infections only achieves these thresholds at impractically low prevalence levels. CONCLUSIONS/SIGNIFICANCE: A target of 5%, 8%, or 11% urogenital schistosomiasis infection prevalence in school-age children could be used to determine whether a geographic area has controlled or eliminated schistosomiasis as a public health problem depending on the local background threshold of microhematuria.

Associations between infection intensity categories and morbidity prevalence in school-age children are much stronger for Schistosoma haematobium than for S. mansoni.

BACKGROUND: World Health Organization (WHO) guidelines for measuring global progress in schistosomiasis control classify individuals with Schistosoma spp. infections based on the concentration of excreted eggs. We assessed the associations between WHO infection intensity categories and morbidity prevalence for selected S. haematobium and S. mansoni morbidities in school-age children. METHODOLOGY: A total of 22,488 children aged 6-15 years from monitoring and evaluation cohorts in Burkina Faso, Mali, Niger, Uganda, Tanzania, and Zambia from 2003-2008 were analyzed using Bayesian logistic regression. Models were utilized to evaluate associations between intensity categories and the prevalence of any urinary bladder lesion, any upper urinary tract lesion, microhematuria, and pain while urinating (for S. haematobium) and irregular hepatic ultrasound image pattern (C-F), enlarged portal vein, laboratory-confirmed diarrhea, and self-reported diarrhea (for S. mansoni) across participants with infection and morbidity data. PRINCIPAL FINDINGS: S. haematobium infection intensity categories possessed consistent morbidity prevalence across surveys for multiple morbidities and participants with light infections had elevated morbidity levels, compared to negative participants. Conversely, S. mansoni infection intensity categories lacked association with prevalence of the morbidity measures assessed. CONCLUSIONS/SIGNIFICANCE: Current status infection intensity categories for S. haematobium were associated with morbidity levels in school-age children, suggesting urogenital schistosomiasis morbidity can be predicted by an individual's intensity category. Conversely, S. mansoni infection intensity categories were not consistently indicative of childhood morbidity at baseline or during the first two years of a preventive chemotherapy control program.

Estimating true prevalence of Schistosoma mansoni from population summary measures based on the Kato-Katz diagnostic technique.

BACKGROUND: The prevalence of Schistosoma mansoni infection is usually assessed by the Kato-Katz diagnostic technique. However, Kato-Katz thick smears have low sensitivity, especially for light infections. Egg count models fitted on individual level data can adjust for the infection intensity-dependent sensitivity and estimate the 'true' prevalence in a population. However, application of these models is complex and there is a need for adjustments that can be done without modeling expertise. This study provides estimates of the 'true' S. mansoni prevalence from population summary measures of observed prevalence and infection intensity using extensive simulations parametrized with data from different settings in sub-Saharan Africa. METHODOLOGY: An individual-level egg count model was applied to Kato-Katz data to determine the S. mansoni infection intensity-dependent sensitivity for various sampling schemes. Observations in populations with varying forces of transmission were simulated, using standard assumptions about the distribution of worms and their mating behavior. Summary measures such as the geometric mean infection, arithmetic mean infection, and the observed prevalence of the simulations were calculated, and parametric statistical models fitted to the summary measures for each sampling scheme. For validation, the simulation-based estimates are compared with an observational dataset not used to inform the simulation. PRINCIPAL FINDINGS: Overall, the sensitivity of Kato-Katz in a population varies according to the mean infection intensity. Using a parametric model, which takes into account different sampling schemes varying from single Kato-Katz to triplicate slides over three days, both geometric and arithmetic mean infection intensities improve estimation of sensitivity. The relation between observed and 'true' prevalence is remarkably linear and triplicate slides per day on three consecutive days ensure close to perfect sensitivity. CONCLUSIONS/SIGNIFICANCE: Estimation of 'true' S. mansoni prevalence is improved when taking into account geometric or arithmetic mean infection intensity in a population. We supply parametric functions and corresponding estimates of their parameters to calculate the 'true' prevalence for sampling schemes up to 3 days with triplicate Kato-Katz thick smears per day that allow estimation of the 'true' prevalence.

Factors affecting the uptake of preventive chemotherapy treatment for schistosomiasis in Sub-Saharan Africa: A systematic review.

BACKGROUND: Schistosomiasis affects nearly 220 million people worldwide, mainly in Sub-Saharan Africa (SSA). Preventive chemotherapy (PC) treatment, through regular mass-drug administration (MDA) of Praziquantel tablets remains the control measure of choice by Ministries of Health. Current guidelines recommend that 75% of school-aged children receive treatment. Many programmes, however, struggle to achieve this target. Given the risk of high reinfection rates, attaining sustained high levels of treatment coverage is essential. This study provides a comprehensive review of the barriers and facilitators operating at different levels of analysis, from the individual to the policy level, conditioning the uptake of PC for schistosomiasis in SSA. METHODOLOGY/PRINCIPAL FINDINGS: A systematic literature search was conducted in several databases for publications released between January 2002 and 2019 that examined factors conditioning the uptake of Praziquantel in the context of MDA campaigns in SSA. A total of 2,258 unique abstracts were identified, of which 65 were selected for full text review and 30 met all eligibility criteria. Joanna Briggs Institute's Critical Appraisal and the Mixed-Methods Assessment tools were used to assess the strength of the evidence. This review was registered with PROSPERO (CRD42017058525). A meta-synthesis approach was used. Results indicated publication bias, with the literature focusing on East African rural settings and evidence at the individual and programmatic levels. The main influencing factors identified included material wellbeing, drug properties, knowledge and attitudes towards schistosomiasis and MDAs, fears of side effects, gender values, community and health systems support, alongside programme design features, like training, sensitisation, and provision of incentives for drug-distributors. The effect of these factors on determining Praziquantel uptake were explored in detail. CONCLUSIONS/SIGNIFICANCE: Multiple determinants of treatment uptake were found in each level of analysis examined. Some of them interact with each other, thus affecting outcomes directly and indirectly. The promotion of context-based transdisciplinary research on the complex dynamics of treatment uptake is not only desirable, but essential, to design effective strategies to attain high levels of treatment coverage.

Lessons from the Field: Integrated survey methodologies for neglected tropical diseases.

The 2021-2030 Neglected Tropical Diseases road map calls for intensified cross-cutting approaches. By moving away from vertical programming, the integration of platforms and intervention delivery aims to improve efficiency, cost-effectiveness and programme coverage. Drawing on the direct experiences of the authors, this article outlines key elements for successful integrated surveys, the challenges encountered, as well as future opportunities and threats to such surveys. There are multiple advantages. Careful planning should ensure that integration does not result in a process that is less efficient, more expensive or that generates data driving less reliable decisions than conducting multiple disease-specific surveys.

Evaluating survey designs for targeting preventive chemotherapy against Schistosoma haematobium and Schistosoma mansoni across sub-Saharan Africa: a geostatistical analysis and modelling study.

BACKGROUND: Schistosomiasis control programmes primarily use school-based surveys to identify areas for mass drug administration of preventive chemotherapy. However, as the spatial distribution of schistosomiasis can be highly focal, transmission may not be detected by surveys implemented at districts or larger spatial units. Improved mapping strategies are required to accurately and cost-effectively target preventive chemotherapy to remaining foci across all possible spatial distributions of schistosomiasis. METHODS: Here, we use geostatistical models to quantify the spatial heterogeneity of Schistosoma haematobium and S. mansoni across sub-Saharan Africa using the most comprehensive dataset available on school-based surveys. Applying this information to parameterise simulations, we assess the accuracy and cost of targeting alternative implementation unit sizes across the range of plausible schistosomiasis distributions. We evaluate the consequences of decisions based on survey designs implemented at district and subdistrict levels sampling different numbers of schools. Cost data were obtained from field surveys conducted across multiple countries and years, with cost effectiveness evaluated as the cost per correctly identified school. RESULTS: Models identified marked differences in prevalence and spatial distributions between countries and species; however, results suggest implementing surveys at subdistrict level increase the accuracy of treatment classifications across most scenarios. While sampling intensively at the subdistrict level resulted in the highest classification accuracy, this sampling strategy resulted in the highest costs. Alternatively, sampling the same numbers of schools currently recommended at the district level but stratifying by subdistrict increased cost effectiveness. CONCLUSIONS: This study provides a new tool to evaluate schistosomiasis survey designs across a range of transmission settings. Results highlight the importance of considering spatial structure when designing sampling strategies, illustrating that a substantial proportion of children may be undertreated even when an implementation unit is correctly classified. Control programmes need to weigh the increased accuracy of more detailed mapping strategies against the survey costs and treatment priorities.

Nationwide Remapping of Schistosoma mansoni Infection in Rwanda Using Circulating Cathodic Antigen Rapid Test: Taking Steps toward Elimination.

The field standard for the detection of Schistosoma mansoni infection is Kato-Katz (KK), although it misses many active infections, especially light infections. In 2014, a reassessment of S. mansoni prevalence was conducted in Rwanda using the more sensitive point-of-care circulating cathodic antigen (POC-CCA) rapid assay. A total of 19,371 children from 399 schools were selected for testing for single urine CCA. Of these, 8,697 children from 175 schools were also tested with single stool double-slide KK. Samples from eight of these 175 schools were tested again with CCA and additionally with the highly specific and sensitive up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay. Latent class analysis was applied to all four test results to assess sensitivity and specificity of POC-CCA and estimate the proportion of trace results from Rwanda likely to be true infections. The overall prevalence of S. mansoni infection in Rwanda when CCA trace results were considered negative was 7.4% (school interquartile range [IQR] 0-8%) and 36.1% (school IQR 20-47%) when trace was considered positive. Prevalence by KK was 2.0% with a mean intensity of infection of 1.66 eggs per gram. The proportion of active infections among children diagnosed with CCA trace was estimated by statistical analysis at 61% (Bayesian credibility interval: 50-72%). These results indicate that S. mansoni infection is still widespread in Rwanda and prevalence is much underestimated by KK testing. Circulating cathodic antigen is an affordable alternative to KK and more suitable for measuring S. mansoni prevalence in low-intensity regions.

Contributions of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) to Schistosomiasis Control and Elimination: Key Findings and Messages for Future Goals, Thresholds, and Operational Research.

Herein, we summarize what we consider are major contributions resulting from the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) program, including its key findings and key messages from those findings. Briefly, SCORE's key findings are as follows: i) biennial mass drug administration (MDA) with praziquantel can control schistosomiasis to moderate levels of prevalence; ii) MDA alone will not achieve elimination; iii) to attain and sustain control throughout endemic areas, persistent hotspots need to be identified following a minimal number of years of annual MDA and controlled through adaptive strategies; iv) annual MDA is more effective than biennial MDA in high-prevalence areas; v) the current World Health Organization thresholds for decision-making based on the prevalence of heavy infections should be redefined; and vi) point-of-care circulating cathodic antigen urine assays are useful for Schistosoma mansoni mapping in low-to-moderate prevalence areas. The data and specimens collected and curated through SCORE efforts will continue to be critical resource for future research. Besides providing useful information for program managers and revision of guidelines for schistosomiasis control and elimination, SCORE research and outcomes have identified additional questions that need to be answered as the schistosomiasis community continues to implement effective, evidence-based programs. An overarching contribution of SCORE has been increased cohesiveness within the schistosomiasis field-oriented community, thereby fostering new and productive collaborations. Based on SCORE's findings and experiences, we propose new approaches, thresholds, targets, and goals for control and elimination of schistosomiasis, and recommend research and evaluation activities to achieve these targets and goals.

Lessons Learned in Conducting Mass Drug Administration for Schistosomiasis Control and Measuring Coverage in an Operational Research Setting.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created to conduct research that could inform programmatic decision-making related to schistosomiasis. SCORE included several large cluster randomized field studies involving mass drug administration (MDA) with praziquantel. The largest of these were studies of gaining or sustaining control of schistosomiasis, which were conducted in five African countries. To enhance relevance for routine practice, the MDA in these studies was coordinated by or closely aligned with national neglected tropical disease (NTD) control programs. The study protocol set minimum targets of at least 90% for coverage among children enrolled in schools and 75% for all school-age children. Over the 4 years of intervention, an estimated 3.5 million treatments were administered to study communities. By year 4, the median village coverage was at or above targets in all studies except that in Mozambique. However, there was often a wide variation behind these summary statistics, and all studies had several villages with very low or high coverage. In studies where coverage was estimated by comparing the number of people treated with the number eligible for treatment, denominator estimation was often problematic. The SCORE experiences in conducting these studies provide lessons for future efforts that attempt to implement strong research designs in real-world contexts. They also have potential applicability to country MDA campaigns against schistosomiasis and other NTDs, most of which are conducted with less logistical and financial support than was available for the SCORE study efforts.

Schistosomiasis - Assessing Progress toward the 2020 and 2025 Global Goals.

BACKGROUND: With the vision of "a world free of schistosomiasis," the World Health Organization (WHO) set ambitious goals of control of this debilitating disease and its elimination as a public health problem by 2020 and 2025, respectively. As these milestones become imminent, and if programs are to succeed, it is important to evaluate the WHO programmatic guidelines empirically. METHODS: We collated and analyzed multiyear cross-sectional data from nine national schistosomiasis control programs (in eight countries in sub-Saharan Africa and in Yemen). Data were analyzed according to schistosome species (Schistosoma mansoni or S. haematobium), number of treatment rounds, overall prevalence, and prevalence of heavy-intensity infection. Disease control was defined as a prevalence of heavy-intensity infection of less than 5% aggregated across sentinel sites, and the elimination target was defined as a prevalence of heavy-intensity infection of less than 1% in all sentinel sites. Heavy-intensity infection was defined as at least 400 eggs per gram of feces for S. mansoni infection or as more than 50 eggs per 10 ml of urine for S. haematobium infection. RESULTS: All but one country program (Niger) reached the disease-control target by two treatment rounds or less, which is earlier than projected by current WHO guidelines (5 to 10 years). Programs in areas with low endemicity levels at baseline were more likely to reach both the control and elimination targets than were programs in areas with moderate and high endemicity levels at baseline, although the elimination target was reached only for S. mansoni infection (in Burkina Faso, Burundi, and Rwanda within three treatment rounds). Intracountry variation was evident in the relationships between overall prevalence and heavy-intensity infection (stratified according to treatment rounds), a finding that highlights the challenges of using one metric to define control or elimination across all epidemiologic settings. CONCLUSIONS: These data suggest the need to reevaluate progress and treatment strategies in national schistosomiasis control programs more frequently, with local epidemiologic data taken into consideration, in order to determine the treatment effect and appropriate resource allocations and move closer to achieving the global goals. (Funded by the Children's Investment Fund Foundation and others.).

Translating preventive chemotherapy prevalence thresholds for Schistosoma mansoni from the Kato-Katz technique into the point-of-care circulating cathodic antigen diagnostic test.

BACKGROUND: Intervention guidelines against Schistosoma mansoni are based on the Kato-Katz technique. However, Kato-Katz thick smears show low sensitivity, especially for light-intensity infections. The point-of-care circulating cathodic antigen (POC-CCA) is a promising rapid diagnostic test detecting antigen output of living worms in urine and results are reported as trace, 1+, 2+, and 3+. The use of POC-CCA for schistosomiasis mapping, control, and surveillance requires translation of the Kato-Katz prevalence thresholds into POC-CCA relative treatment cut-offs. Furthermore, the infection status of egg-negative but antigen-positive individuals and the intensity-dependent sensitivity of POC-CCA should be estimated to determine its suitability for verification of disease elimination efforts. METHODOLOGY: We used data from settings in Africa and the Americas characterized by a wide range of S. mansoni endemicity. We estimated infection intensity-dependent sensitivity and specificity of each test at the unit of the individual, using a hierarchical Bayesian egg-count model that removes the need to define a 'gold' standard applied to data with multiple Kato-Katz thick smears and POC-CCA urine cassette tests. A simulation study was carried out based on the model estimates to assess the relation of the two diagnostic tests for different endemicity scenarios. PRINCIPAL FINDINGS: POC-CCA showed high specificity (> 95%), and high sensitivity (> 95%) for moderate and heavy infection intensities, and moderate sensitivity (> 75%) for light infection intensities, and even for egg-negative but antigen-positive infections. A 10% duplicate slide Kato-Katz thick smear prevalence corresponded to a 15-40% prevalence of ≥ trace-positive POC-CCA, and 10-20% prevalence of ≥ 1+ POC-CCA. The prevalence of ≥ 2+ POC-CCA corresponded directly to single slide Kato-Katz prevalence for all prevalence levels. CONCLUSIONS/SIGNIFICANCE: The moderate sensitivity of POC-CCA, even for very light S. mansoni infections where the sensitivity of Kato-Katz is very low, and the identified relationship between Kato-Katz and POC-CCA prevalence thresholds render the latter diagnostic tool useful for surveillance and initial estimation of elimination of S. mansoni. For prevalence below 10% based on a duplicate slide Kato-Katz thick smear, we suggest using POC-CCA including trace results to evaluate treatment needs and propose new intervention thresholds that need to be validated in different settings.

Assessing the benefits of five years of different approaches to treatment of urogenital schistosomiasis: A SCORE project in Northern Mozambique.

BACKGROUND: In Mozambique, schistosomiasis is highly endemic across the whole country. The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) coordinates a five-year study that has been implemented in various African countries, including Mozambique. The overall goal of SCORE was to better understand how to best apply preventive chemotherapy with praziquantel (PZQ) for schistosomiasis control by evaluating the impact of alternative treatment approaches. METHODS: This was a cluster-randomised trial that compared the impact of different treatment strategies in study areas with prevalence among school children of ≥21% S. haematobium infection by urine dipstick. Each village was randomly allocated to one of six possible combinations of community-wide treatment (CWT), school-based treatment (SBT), and/or drug holidays over a period of four years, followed by final data collection in the fifth year. The most intense intervention arm involved four years of CWT, while the least intensive arm involved two years of SBT followed by two consecutive years of PZQ holiday. Each study arm included 25 villages randomly assigned to one of the six treatment arms. The primary outcome of interest was change in prevalence and intensity of S. haematobium among 100 children aged 9-to-12-years that were sampled each year in every village. In addition to children aged 9-to-12 years, 100 children aged 5-8 years in their first-year of school and 50 adults (aged 20-55 years) were tested in the first and final fifth year of the study. Prevalence and intensity of S. haematobium infection was evaluated by two filtrations, each of 10mL, from a single urine specimen. PRINCIPAL FINDINGS: In total, data was collected from 81,167 individuals across 149 villages in ten districts of Cabo Delgado province, Northern Mozambique. Overall PZQ treatment resulted in a significant reduction in the prevalence of S. haematobium infection from Year 1 to Year 5, where the average prevalence went from 60.5% to 38.8%, across all age groups and treatment arms. The proportion of those heavily infected also reduced from 17.6% to 11.9% over five years. There was a significantly higher likelihood of males being infected than females at baseline, but no significant difference between the sexes in their response to treatment. The only significant response based on a study arm was seen in both the 9-to-12-year-old and first-year cross sections, where two consecutive treatment holidays resulted in a significantly higher final prevalence of S. haematobium than no treatment holidays. When the arms were grouped together, four rounds of treatment (regardless of whether it was CWT or SBT), however, did result in a significantly greater reduction in S. haematobium prevalence than two rounds of treatment (i.e. with two intermittent or consecutive holiday years) over a five-year period. CONCLUSIONS: Although PC was successful in reducing the burden of active infection, even among those heavily infected, annual CWT did not have a significantly greater impact on disease prevalence or intensity than less intense treatment arms. This may be due to extremely high starting prevalence and intensity in the study area, with frequent exposure to reinfection, or related to challenges in achieving high treatment coverage More frequent treatment had a greater impact on prevalence and intensity of infection when arms were grouped by number of treatments, however, cost efficiency was greater in arms only receiving two treatments. Finally, a significant reduction in prevalence of S. haematobium was seen in adults even in the SBT arms implying the rate of transmission in the community had been decreased, even where only school children have been treated, which has significant logistical and cost-saving implications for a national control programme in justifying CWT.