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. Author summary: The World Health Organization (WHO) has defined goals for schistosomiasis morbidity control to be reached by 2025 that are based on preventive chemotherapy. Intervention thresholds for Schistosoma mansoni are currently defined for prevalence measured by stool microscopy using the Kato-Katz technique. However, the Kato-Katz technique shows low sensitivity, particularly for the detection of light-intensity infections. Replacing it with the semi-quantitative point-of-care circulating cathodic antigen (POC-CCA) urine cassette test requires translation of the thresholds and precise characterization of the diagnostic sensitivity and specificity. In this study, we applied a novel egg-count model to a suite of data obtained from different settings in Africa and the Americas with diverse endemicity levels. We used a simulation study to infer on the relation between Kato-Katz and POC-CCA prevalence. Based on our study, we were able to provide recommendations for POC-CCA thresholds taking into account semi-quantitative results of the test. We found that a S. mansoni prevalence of 10% based on duplicate slide Kato-Katz thick smear is equivalent to 15–40% POC-CCA prevalence when trace results are considered positive and to 10–20% POC-CCA prevalence when trace results are considered negative. Our results have important bearings for mapping, control, surveillance, and verification of elimination of intestinal schistosomiasis.