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Efforts to control Schistosoma mansoni infection depend on the ability of programs to effectively detect and quantify infection levels and adjust programmatic approaches based on these levels and program goals. One of the three major objectives of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) has been to develop and/or evaluate tools that would assist Neglected Tropical Disease program managers in accomplishing this fundamental task. The advent of a widely available point-of-care (POC) assay to detect schistosome circulating cathodic antigen (CCA) in urine with a rapid diagnostic test (the POC-CCA) in 2008 led SCORE and others to conduct multiple evaluations of this assay, comparing it with the Kato-Katz (KK) stool microscopy assay-the standard used for more than 45 years. This article describes multiple SCORE-funded studies comparing the POC-CCA and KK assays, the pros and cons of these assays, the use of the POC-CCA assay for mapping of S. mansoni infections in areas across the spectrum of prevalence levels, and the validation and recognition that the POC-CCA, although not infallible, is a highly useful tool to detect low-intensity infections in low-to-moderate prevalence areas. Such an assay is critical, as control programs succeed in driving down prevalence and intensity and seek to either maintain control or move to elimination of transmission of S. mansoni .

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.

Forty-five Schistosoma mansoni egg-negative/circulating cathodic antigen (CCA) low (Trace-1+) positive children in areas of very low prevalence were followed up daily for 30 days. Stool and urine specimens were collected and examined each day from each child. At the midpoint of the study, three egg-positive control persons with light intensity infection were included in the protocol. Stool samples were examined by the Kato-Katz (four slides/stool sample) technique and all S. mansoni egg-negative stools were further tested by the "miracidia hatching test" (MHT). Urine samples were examined by the point-of-care CCA assay (POC-CCA). Over 30 days, only one of 1,338 consecutive stool samples from study subjects was S. mansoni egg and MHT positive (0.07%). Egg counts fluctuated daily in stools from positive controls and S. mansoni miracidia were detected in all but two samples by the MHT. Point-of-care-circulating cathodic antigen bands were scored from G1 to G10 and then translated to standard Trace, 1+, 2+, 3+ banding patterns. In two districts, the POC-CCA assays were Trace or 1+ for both the study children and the positive controls. In the third district, the POC-CCA assays were Trace or 1+ for the study children and 1+ or 2+ for the positive control. We conclude that in areas with extremely low prevalence S. mansoni egg-negative and CCA-Trace or 1+ children are unlikely to pose substantial risks to continued transmission of schistosomiasis. In this setting, POC-CCA Trace or 1+ readings are likely to be false positives or perhaps represent low-level single-sex schistosome infections.

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., Competing Interests: The authors have declared that no competing interests exist.

In line with WHO recommendations on elimination of schistosomiasis, accurate identification of all areas of residual transmission is a key step to design and implement measures aimed at interrupting transmission in low-endemic settings. To this purpose, we assessed the prevalence of active S. mansoni infection in five pilot governorates in the Nile Delta of Egypt by examining schoolchildren (6-15 years) using the Urine-Circulating Cathodic Antigen (Urine-CCA) cassette test; we also carried out the standard Kato-Katz (KK) thick smear, the monitoring and evaluation tool employed by Egypt's national schistosomiasis control programme. Prevalence rates determined by the Urine-CCA test for all governorates were higher than those determined by KK (p<0.01). Of 35 districts surveyed in the five governorates, S. mansoni infection was detected in 19 districts (54.3%) using KK, and in 31 districts (88.6%) by Urine-CCA (χ2=9.94; P=0.0016). S. mansoni infections were detected by Urine-CCA, but not by KK in 12 districts (34.3%), and infection was not detected by either of the two diagnostic methods in four districts in Qalyubia governorate. Males and higher age-groups have significantly higher Urine-CCA prevalence rates. Based on the findings of the current S. mansoni mapping exercise, authorities of the Ministry of Health and Population (MoHP) adopted a new elimination strategy by readjusting thresholds for mass treatment with praziquantel and targeting all transmission areas. MoHP is now planning to remap in all other endemic governorates using Urine-CCA with the aim of identifying all areas of transmission where the elimination strategy should be applied., (Copyright © 2016 Elsevier B.V. All rights reserved.)