Low specificity of point-of-care circulating cathodic antigen (POC[sbnd]CCA) diagnostic test in a non-endemic area for schistosomiasis mansoni in Brazil

This work was funded by the Secretaria de Vigil?ncia em Sa?de / Fundo Nacional de Sa?de / Minist?rio da Sa?de (SVS/FNS/MS) - [TED/FNS: 118/2017; SIAFI: 691919/25000.479741/2017?05]. Universidade Federal do Esp?rito Santo.Center for Health Sciences. Infectious Diseases Unit. Vit?ria, ES, Brazil / Pont?ficia Universidade Cat?lica do Rio Grande do Sul. School of Sciences. Research Group on Biomedical Parasitology. Porto Alegre, RS, Brazil. Pont?ficia Universidade Cat?lica do Rio Grande do Sul. School of Sciences. Research Group on Biomedical Parasitology. Porto Alegre, RS, Brazil. Pont?ficia Universidade Cat?lica do Rio Grande do Sul. School of Sciences. Research Group on Biomedical Parasitology. Porto Alegre, RS, Brazil. Pont?ficia Universidade Cat?lica do Rio Grande do Sul. School of Sciences. Research Group on Biomedical Parasitology. Porto Alegre, RS, Brazil. Pont?ficia Universidade Cat?lica do Rio Grande do Sul. School of Sciences. Research Group on Biomedical Parasitology. Porto Alegre, RS, Brazil. Pont?ficia Universidade Cat?lica do Rio Grande do Sul. School of Sciences. Research Group on Biomedical Parasitology. Porto Alegre, RS, Brazil. Universidade Federal do Cear?. Department of Clinical and Toxicological Analyses. Fortaleza, CE, Brazil. Funda??o Oswaldo Cruz.Ren? Rachou Institute. Belo Horizonte, MG, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Funda??o Oswaldo Cruz. Oswaldo Cruz Institute. Rio de Janeiro, RJ, Brazil. Funda??o Oswaldo Cruz.Ren? Rachou Institute. Belo Horizonte, MG, Brazil. Funda??o Oswaldo Cruz. Gon?alo Muniz Institute. Salvador, BA, Brazil. Funda??o Oswaldo Cruz. Gon?alo Muniz Institute. Salvador, BA, Brazil / Federal University of Bahia. Faculty of Medicine of Bahia. Salvador, BA, Brazil / Yale University. School of Public Health. Department of Epidemiology of Microbial Diseases. New Haven, CT, United States of America. Funda??o Oswaldo Cruz. Oswaldo Cruz Institute. Rio de Janeiro, RJ, Brazil. A point-of-care test for detecting schistosome circulating cathodic antigen in urine (POC[sbnd]CCA) has been proposed for mapping infection and defining prevalence thresholds for mass drug administration (MDA). However, there is increasing evidence that POC[sbnd]CCA may yield false-positive results, which requires rigorous specificity evaluation in non-endemic areas. POC[sbnd]CCA was applied in an area known to be free from infection and devoid of any condition for schistosomiasis transmission as part of a multicentre study to evaluate the performance of POC[sbnd]CCA in Brazil's low or potentially endemic settings. Besides POC[sbnd]CCA detection in urine, a search for eggs in stool was performed by Kato-Katz (KK) and Helmintex (HTX) methods. One-hundred-and-seventy-four participants returned urine samples, 140 of which delivered stool samples. All these were HTX-negative for Schistosoma mansoni, and all 118 tested with KK were negative for both S. mansoni and soil-transmitted helminths. POC[sbnd]CCA results from freshly collected urine yielded a specificity of 62.1% (95% CI: 53.6% - 70.2%), taking trace outcomes as positive according to the manufacturer's instructions. Retesting urine from the 140 HTX-negatives after one-year storage at -20 ?C with two new POC[sbnd]CCA batches simultaneously yielded significantly different specificities (34.3%; 95%CI: 26.5% ? 42.8% and 75.0%; 95% CI: 67.0% - 81.9%). These two batches had a weak agreement (Cohen's kappa: 0.56; 95%CI: 0.44?0.68) among the 174 urine samples retested. At present, POC[sbnd]CCA cannot be recommended either as a cut-off point for MDA or a reliable diagnostic tool for treatment of the infection carriers (selective chemotherapy) in low endemic areas and at final stages of transmission interruption. Manufacturers should be required to optimize production standardization and to assure quality and reproducibility of the test. Extended rigorous performance evaluations by different users from different regions are needed before POC[sbnd]CCA is widely recommended