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      Concordance of the point-of-care circulating cathodic antigen test for the diagnosis of intestinal schistosomiasis in a low endemicity area

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          Abstract

          Background

          The Kato-Katz technique is recommended worldwide for the diagnosis of intestinal schistosomiasis, detecting parasite eggs in feces of infected people. However, new tests have been developed in order to facilitate diagnosis, e.g. by detection of specific antigens secreted by schistosomes, such as the circulating cathodic antigen (CCA). The aim of this study was to evaluate the performance of the point-of-care circulating cathodic antigen test (POC-CCA) compared to the Kato-Katz technique in a low prevalence area in the Amazon Region, located in the municipality of Primavera, State of Pará, Brazil.

          Methods

          Positivity rates of the POC-CCA test and the Kato-Katz technique were calculated. The sensitivity, specificity, accuracy and kappa coefficient were determined by comparing both methods. The reference standard was established using 16 Kato-Katz slides, 12 of the first fecal sample, two of the second and two of the third one. The study also included the concordance between POC-CCA results and different numbers and combinations of Kato-Katz slides.

          Results

          The prevalence of schistosomiasis according to the reference standard or POC-CCA test reached a rate of 9.4% or 23.9%, respectively, among a total of 372 participants. The positivity rates by the Kato-Katz technique increased from 2.4 to 9.4%, according to the increase in the number of slides examined and fecal samples collected. A sensitivity of 55.6%, specificity 76.9%, accuracy 76% and κ coefficient of 0.06 was observed by comparing one slide of the first sample and POC-CCA. Comparing 6 slides from three different samples, two slides of each, with POC-CCA resulted in a sensitivity of 58.3%, specificity 78.4%, accuracy 77% and κ coefficient of 0.16. Finally, the comparison of 16 slides from three different samples with POC-CCA revealed a sensitivity of 65.7%, specificity 80.4%, accuracy 79%, and κ coefficient of 0.27.

          Conclusions

          The immunochromatographic test has the potential to be an important tool to combat schistosomiasis because of its practicality and applicability but should be applied with caution in low prevalence areas and in programs that aim to eliminate this disease.

          Trial registration

          CAAE#21824513.9.0000.5091. January 31st, 2014.

          Electronic supplementary material

          The online version of this article (10.1186/s40249-019-0551-7) contains supplementary material, which is available to authorized users.

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          Most cited references26

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          Relative contribution of day-to-day and intra-specimen variation in faecal egg counts of Schistosoma mansoni before and after treatment with praziquantel.

          There is evidence that faecal egg counts of Schistosoma mansoni vary considerably from day to day, which results in poor sensitivity of single stool readings. Intra-specimen variation of S. mansoni egg counts may also be considerable, but has previously been considered as the less important component. We quantified the relative contribution of these two sources of variation among 96 schoolchildren from an area in Cĵte d'Ivoire highly endemic for S. mansoni. Stool specimens were collected over 5 consecutive days, and 5 egg-counts were made in each specimen by the Kato-Katz technique. The point prevalence of the first sample was 42.7% and the cumulative prevalence after the maximum sampling effort was 88.5%. Using generalized linear mixed models we found that the presence of S. mansoni eggs in a stool sample varied much more between days than within specimens, indicating that stool sample examination over multiple days is required for accurate prevalence estimates. However, using the same approach, we found that among infected children intra-specimen variation in egg counts was 4.3 times higher than day-to-day variation. After praziquantel administration, day-to-day variation was more important than before, since most infections were very light and thus likely to be missed altogether by stool examination on a single day. We conclude that diagnostic sensitivity in high transmission areas is maximized by making several stool readings on several days, but examining 1 stool specimen several times can make reasonable estimates of infection intensity.
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            Schistosomiasis is more prevalent than previously thought: what does it mean for public health goals, policies, strategies, guidelines and intervention programs?

            Mapping and diagnosis of infections by the three major schistosome species (Schistosoma haematobium, S. mansoni and S. japonicum) has been done with assays that are known to be specific but increasingly insensitive as prevalence declines or in areas with already low prevalence of infection. This becomes a true challenge to achieving the goal of elimination of schistosomiasis because the multiplicative portion of the life-cycle of schistosomes, in the snail vector, favors continued transmission as long as even a few people maintain low numbers of worms that pass eggs in their excreta. New mapping tools based on detection of worm antigens (circulating cathodic antigen – CCA; circulating anodic antigen – CAA) in urine of those infected are highly sensitive and the CAA assay is reported to be highly specific. Using these tools in areas of low prevalence of all three of these species of schistosomes has demonstrated that more people harbor adult worms than are regularly excreting eggs at a level detectable by the usual stool assay (Kato-Katz) or by urine filtration. In very low prevalence areas this is sometimes 6- to10-fold more. Faced with what appears to be a sizable population of “egg-negative/worm-positive schistosomiasis” especially in areas of very low prevalence, national NTD programs are confounded about what guidelines and strategies they should enact if they are to proceed toward a goal of elimination. There is a critical need for continued evaluation of the assays involved and to understand the contribution of this “egg-negative/worm-positive schistosomiasis” condition to both individual morbidity and community transmission. There is also a critical need for new guidelines based on the use of these more sensitive assays for those national NTD programs that wish to move forward to strategies designed for elimination. Electronic supplementary material The online version of this article (doi:10.1186/s40249-017-0275-5) contains supplementary material, which is available to authorized users.
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              Comparison of Schistosoma mansoni Prevalence and Intensity of Infection, as Determined by the Circulating Cathodic Antigen Urine Assay or by the Kato-Katz Fecal Assay: A Systematic Review

              The relationship between results from Kato-Katz (KK) fecal microscopy and urine-based point-of-care circulating cathodic antigen (POC-CCA) assays for Schistosoma mansoni infection remains a critical issue. This systematic literature review of 25 published papers compares prevalence of S. mansoni infection by KK with that by the POC-CCA assay. Nineteen published studies met our inclusion criteria for data extraction and analysis. Above a prevalence of 50% by KK, KK and POC-CCA results yielded essentially the same prevalence. Below 50% prevalence by KK, the prevalence by the POC-CCA assay was between 1.5- and 6-fold higher and increased as prevalence by KK decreased. Five of nine publications met inclusion criteria for extractable data on intensity of S. mansoni infection by KK assay and visual band density using the POC-CCA assay. A clear positive relationship exists between intensity by the KK and POC-CCA assays. This systematic review indicates that below 50% prevalence, the POC-CCA assay is much more sensitive than the KK assay. However, the existing data are inadequate to precisely define the relationship between POC-CCA and KK at lower levels of KK prevalence. More studies directly comparing the two assays in low-prevalence areas are essential to inform decision-making by national schistosomiasis control programs.
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                Author and article information

                Contributors
                55 91 98224-2075 , rodrigo.bio.uepa@gmail.com
                isabellediias@hotmail.com
                alvaroluan@hotmail.com
                biancacontente@hotmail.com
                joycenogueira@iec.pa.gov.br
                tatyellenoliveira@iec.gov.br
                stefan.geiger76@gmail.com
                martinenk@iec.pa.gov.br , marenk.iec@gmail.com
                Journal
                Infect Dis Poverty
                Infect Dis Poverty
                Infectious Diseases of Poverty
                BioMed Central (London )
                2095-5162
                2049-9957
                30 May 2019
                30 May 2019
                2019
                : 8
                : 37
                Affiliations
                [1 ]GRID grid.442052.5, Programa de Pós-Graduação Strictu Sensu em Biologia Parasitária na Amazônia da Universidade do Estado do Pará, ; Tv. Perebebuí, 2623 - Marco, Belém, PA 66087 Brazil
                [2 ]Laboratório de Parasitoses Intestinais, Esquistossomose e Malacologia (LPIEM), Secção de Parasitologia, Instituto Evandro Chagas/SVS/MS, Ananindeua, Pará Brazil
                [3 ]ISNI 0000 0001 2181 4888, GRID grid.8430.f, Departamento de Parasitologia, , Universidade Federal de Minas Gerais, ; Belo Horizonte, Minas Gerais Brazil
                Author information
                http://orcid.org/0000-0003-2197-7323
                Article
                551
                10.1186/s40249-019-0551-7
                6542115
                31142379
                c751d3dd-930e-450e-86f1-6c2084fe3d33
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 29 January 2019
                : 16 May 2019
                Funding
                Funded by: Fundação de Amparo à Pesquisa do Estado do Pará (BR)
                Award ID: 0042017
                Funded by: FundRef http://dx.doi.org/10.13039/501100003545, Ministério da Ciência, Tecnologia e Inovação;
                Award ID: MCTI/CNPq/MS-SCTIE-Decit n 40/2012
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                schistosoma mansoni,kato-katz,poc-cca,accuracy,diagnosis,low prevalence area

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