Reproducibility matters: intra- and inter-sample variation of the point-of-care circulating cathodic antigen test (POC-CCA) in two Schistosoma mansoni endemic areas in Uganda

Kabbas-Piñango, E. , Arinaitwe, M., van Dam, G. J., Moses, A., Namukuta, A., Nankasi, A. B., Khayinja Mwima, N., Besigye, F., Prada, J. M. and Lamberton, P. H. L. (2023) Reproducibility matters: intra- and inter-sample variation of the point-of-care circulating cathodic antigen test (POC-CCA) in two Schistosoma mansoni endemic areas in Uganda. Philosophical Transactions of the Royal Society B: Biological Sciences, 378(1887), 20220275. (doi: 10.1098/rstb.2022.0275) (PMID:37598698)

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Abstract

Over 240 million people are infected with schistosomiasis. Detecting Schistosoma mansoni eggs in stool using Kato–Katz thick smears (Kato-Katzs) is highly specific but lacks sensitivity. The urine-based point-of-care circulating cathodic antigen test (POC-CCA) has higher sensitivity, but issues include specificity, discrepancy between batches and interpretation of trace results. A semi-quantitative G-score and latent class analyses making no assumptions about trace readings have helped address some of these issues. However, intra-sample and inter-sample variation remains unknown for POC-CCAs. We collected 3 days of stool and urine from 349 and 621 participants, from high- and moderate-endemicity areas, respectively. We performed duplicate Kato-Katzs and one POC-CCA per sample. In the high-endemicity community, we also performed three POC-CCA technical replicates on one urine sample per participant. Latent class analysis was performed to estimate the relative contribution of intra- (test technical reproducibility) and inter-sample (day-to-day) variation on sensitivity and specificity. Within-sample variation for Kato-Katzs was higher than between-sample, with the opposite true for POC-CCAs. A POC-CCA G3 threshold most accurately assesses individual infections. However, to reach the WHO target product profile of the required 95% specificity for prevalence and monitoring and evaluation, a threshold of G4 is needed, but at the cost of reducing sensitivity. This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’.

Item Type:Articles
Additional Information:This work was supported by E.K.-P.'s Medical Research Scotland PhD studentship awarded to P.H.L.L., the primary supervisor (MRS PhD-1183-2017); the European Research Council (ERC Starting Grant awarded to P.H.L.L., SCHISTO_PERSIST 680088); and the Engineering and Physical Sciences Research Council (EPSRC EP/T003618/1 awarded to J.M.P. and P.H.L.L.).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lamberton, Professor Poppy and Kabbas Piñango, Elías
Authors: Kabbas-Piñango, E., Arinaitwe, M., van Dam, G. J., Moses, A., Namukuta, A., Nankasi, A. B., Khayinja Mwima, N., Besigye, F., Prada, J. M., and Lamberton, P. H. L.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Philosophical Transactions of the Royal Society B: Biological Sciences
Publisher:The Royal Society
ISSN:0962-8436
ISSN (Online):1471-2970
Published Online:21 August 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Philosophical Transactions of the Royal Society B: Biological Sciences 378(1887):20220275
Publisher Policy:Reproduced with the permission of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172876SCHISTO-PERSISTPoppy LambertonEuropean Research Council (ERC)680088Institute of Biodiversity, Animal Health and Comparative Medicine
306568Mathematical tools to inform sustainable interventions against schistosomiasis infections in UgandaPoppy LambertonEngineering and Physical Sciences Research Council (EPSRC)88608 (EP/T003618/1)SHW - Health Economics & Health Technology Assessment