Reconciling egg- and antigen-based estimates of Schistosoma mansoni clearance and reinfection: a modelling study

Clark, J. et al. (2021) Reconciling egg- and antigen-based estimates of Schistosoma mansoni clearance and reinfection: a modelling study. Clinical Infectious Diseases, (doi: 10.1093/cid/ciab679) (PMID:34358299) (In Press)

[img] Text
248900.pdf - Accepted Version
Available under License Creative Commons Attribution.

412kB

Abstract

Background: 240-million people have schistosomiasis despite decades of interventions. Infections cannot be directly observed, and egg-based Kato-Katz thick smears lack sensitivity, impacting treatment efficacy and reinfection rate estimates. The Point-of-Care Circulating Cathodic Antigen test (POC-CCA) is advocated as an improvement upon the Kato-Katz, however improved estimates are limited by ambiguities in the interpretation of Trace results. Method: We collected repeated Kato-Katz counts from 210 school-aged children and scored POC-CCAs according to manufacturer’s guidelines (POC-CCA+) and the externally developed G-Score. We used Hidden Markov Models parameterised with Kato-Katz; Kato-Katz and POC-CCA+; and Kato-Katz and G-Scores, inferring latent clearance and reinfection probabilities at four timepoints over six-months through a more formal statistical reconciliation of these diagnostics than previously conducted. Our approach required minimal but robust assumptions regarding Trace interpretations. Results: Antigen-based models estimated higher infection prevalence across all timepoints compared with the Kato-Katz model, corresponding to lower clearance and higher reinfection estimates. Specifically, pre-treatment prevalence estimates were 85% (Kato-Katz; 95% CI: 79-92%), 99% (POC-CCA+; 97-100%) and 98% (G-Score; 95-100%). Post-treatment, 93% (Kato-Katz; 88-96%), 72% (POC-CCA+; 64-79%) and 65% (G-Score; 57-73%) of those infected were estimated to clear infection. Of those who cleared infection, 35% (Kato-Katz; 27-42%), 51% (POC-CCA+; 41-62%) and 44% (G-Score; 33-55%) were estimated to have been reinfected by nine-weeks. Conclusion: Treatment impact was shorter-lived than only Kato-Katz-based estimates suggested, with lower clearance and rapid reinfection. Three-weeks-post-treatment captured longer-term clearance dynamics. Nine-weeks-post-treatment captured reinfection, but alone could not discern between failed clearance and rapid reinfection. Therefore, frequent sampling is required to understand these important epidemiological dynamics.

Item Type:Articles
Additional Information:This work was supported by: European Research Council Starting Grant [grant number SCHISTO_PERSIST_680088 to PHLL]; Wellcome [grant number 204820/Z/16/Z to PHLL]; Engineering and Physical Sciences Research Council (EPSRC) [grant number EP/T003618/1 to JMP and PHLL]; Medical Research Council [grant number MR/P025447/1 to PHLL] and EPSRC [grant number EP/R01437X/1 to PI J. Cooper and JMP, University of Glasgow].
Status:In Press
Refereed:Yes
Glasgow Author(s) Enlighten ID:Francoeur, Ms Rachel and Carruthers, Dr Lauren and Clark, Dr Jessica and Lamberton, Dr Poppy and Faust, Christina
Authors: Clark, J., Arinaitwe, M., Nankasi, A., Faust, C. L., Moses, A., Ajambo, D., Besigye, F., Atuhaire, A., Wamboko, A., Carruthers, L. V., Francoeur, R., Tukahebwe, E. M., Prada, J. M., and Lamberton, P. H.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Clinical Infectious Diseases
Publisher:Oxford University Press
ISSN:1058-4838
ISSN (Online):1537-6591
Published Online:06 August 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Clinical Infectious Diseases 2021
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172876SCHISTO-PERSISTPoppy LambertonEuropean Research Council (ERC)680088Institute of Biodiversity, Animal Health and Comparative Medicine
173707Institutional Strategic Support Fund (2016)Anna DominiczakWellcome Trust (WELLCOTR)204820/Z/16/ZInstitute of Cardiovascular & Medical Sciences
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
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
300573Novel low cost diagnostic tools and their impact in AfricaJonathan CooperEngineering and Physical Sciences Research Council (EPSRC)EP/R01437X/1ENG - Biomedical Engineering