Translating from egg-to antigen-based indicators for Schistosoma mansoni elimination targets: a Bayesian latent class analysis study

Clark, J. et al. (2022) Translating from egg-to antigen-based indicators for Schistosoma mansoni elimination targets: a Bayesian latent class analysis study. Frontiers in Tropical Diseases, 3, 825721. (doi: 10.3389/fitd.2022.825721) (PMID:35784267) (PMCID:PMC7612949)

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Abstract

Schistosomiasis is a parasitic disease affecting over 240-million people. World Health Organization (WHO) targets for Schistosoma mansoni elimination are based on Kato-Katz egg counts, without translation to the widely used, urine-based, point-of-care circulating cathodic antigen diagnostic (POC-CCA). We aimed to standardize POC-CCA score interpretation and translate them to Kato-Katz-based standards, broadening diagnostic utility in progress towards elimination. A Bayesian latent-class model was fit to data from 210 school-aged-children over four timepoints pre- to six-months-post-treatment. We used 1) Kato-Katz and established POC-CCA scoring (Negative, Trace, +, ++ and +++), and 2) Kato-Katz and G-Scores (a new, alternative POC-CCA scoring (G1 to G10)). We established the functional relationship between Kato-Katz counts and POC-CCA scores, and the score-associated probability of true infection. This was combined with measures of sensitivity, specificity, and the area under the curve to determine the optimal POC-CCA scoring system and positivity threshold. A simulation parametrized with model estimates established antigen-based elimination targets. True infection was associated with POC-CCA scores of ≥ + or ≥G3. POC-CCA scores cannot predict Kato-Katz counts because low infection intensities saturate the POC-CCA cassettes. Post-treatment POC-CCA sensitivity/specificity fluctuations indicate a changing relationship between egg excretion and antigen levels (living worms). Elimination targets can be identified by the POC-CCA score distribution in a population. A population with ≤2% ++/+++, or ≤0.5% G7 and above, indicates achieving current WHO Kato-Katz-based elimination targets. Population-level POC-CCA scores can be used to access WHO elimination targets prior to treatment. Caution should be exercised on an individual level and following treatment, as POC-CCAs lack resolution to discern between WHO Kato-Katz-based moderate- and high-intensity-infection categories, with limited use in certain settings and evaluations.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Faust, Christina and Francoeur, Ms Rachel and Carruthers, Dr Lauren and Clark, Dr Jessica and Lamberton, Professor Poppy and Prada Jimenez de Cisneros, Dr Joaquin
Authors: Clark, J., Moses, A., Nankasi, A., Faust, C. L., Adriko, M., Ajambo, D., Besigye, F., Atuhaire, A., Wamboko, A., Rowel, C., Carruthers, L. V., Francoeur, R., Tukahebwa, E. M., Lamberton, P. H.L., and Prada, J. M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Frontiers in Tropical Diseases
Publisher:Frontiers Media
ISSN:2673-7515
ISSN (Online):2673-7515
Copyright Holders:Copyright © 2022 Clark, Moses, Nankasi, Faust, Adriko, Ajambo, Besigye, Atuhaire, Wamboko, Rowel, Carruthers, Francoeur, Tukahebwa, Lamberton and Prada
First Published:First published in Frontiers in Tropical Diseases 3: 825721
Publisher Policy:Reproduced under a Creative Commons License
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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
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306568Mathematical tools to inform sustainable interventions against schistosomiasis infections in UgandaPoppy LambertonEngineering and Physical Sciences Research Council (EPSRC)88608 (EP/T003618/1)HW - Health Economics and Health Technology Assessment
300573Novel low cost diagnostic tools and their impact in AfricaJonathan CooperEngineering and Physical Sciences Research Council (EPSRC)EP/R01437X/1ENG - Biomedical Engineering
174071Cultural, social and economic influences on ongoing schistosomiasis transmission, despite a decade of mass treatment, and the potential for changePoppy LambertonMedical Research Council (MRC)MR/P025447/1Institute of Biodiversity, Animal Health and Comparative Medicine