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

Abstract

BackgroundIntervention 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.MethodologyWe 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 findingsPOC-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/significanceThe 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.

An outbreak of intestinal schistosomiasis, alongside increasing urogenital schistosomiasis prevalence, in primary school children on the shoreline of Lake Malawi, Mangochi District, Malawi

“…Whilst the debate on how to interpret 'trace' reactions of urine-CCA dipsticks continues, a 'positive' reaction is considered solid evidence of active intestinal schistosomiasis [12]. With no association detected between urogenital schistosomiasis and urine-CCA in our study, we conclude that urine-CCA tests are highly speci c for S. mansoni detection, with 'trace' results indicating light sub-clinical infections, with sub-patent egg outputs.…”

“…Risk factors analyses for morbidity associated with urogenital and intestinal schistosomiasis upon detection of microhematuria and FOB, respectively. α all total of 200 FOB tests were available being used at Samama, Mchoka and MOET schools b a trace result was considered here as not infected, only +ve urine CCA-dipstick scorings were considered infected; our conservative approach was based upon correlates of urine CCA-dipsticks and duplicate Kato-Katz comparisons, with ova-patent prevalence of S. mansoni being ≥ 20%, see Bärenbold et al [12]. Figures Figure 1 A study ow-chart of the objectives, sample size and methods used during this investigation.…”

“…For detection of intestinal schistosomiasis, two drops of urine were applied to a CCA-dipstick (Rapid Medical Diagnostics, Pretoria, South Africa). Results were scored visually against a reference colour photograph as 'negative', 'trace' or 'positive' and cross-checked [12]. To augment urine CCA-dipsticks, onsite inspection of collected stool was performed with parasitological methods; at Mchoka, Samama, MOET and Koche schools, all children were asked to provide a stool sample with a total of 265 specimens obtained (see Table 1).…”

Schistosoma mansoni Infection as a Predictor of Low Aerobic Capacity in Ugandan Children

“…Urine-CCA has the advantage of detecting light intensity infections which may be missed using the traditional Kato-Katz technique. 37 The test band reaction intensity was semiquantitatively graded as negative (−), trace positive (tr), single positive (+), double positive (++), and triple positive (+++).…”

An outbreak of intestinal schistosomiasis, alongside increasing urogenital schistosomiasis prevalence, in primary school children on the shoreline of Lake Malawi, Mangochi District, Malawi

“…For detection of intestinal schistosomiasis, two drops of urine were applied to a CCA-dipstick (Rapid Medical Diagnostics, Pretoria, South Africa). Results were scored visually against a reference colour photograph as 'negative', 'trace' or 'positive' and cross-checked [12]. To augment urine CCA-dipsticks, on-site inspection of Table 1).…”