Identification and validation of a novel panel of Plasmodium knowlesi biomarkers of serological exposure

Herman, L. S., Fornace, K. , Phelan, J., Grigg, M. J., Anstey, N. M., William, T., Moon, R. W., Blackman, M. J., Drakeley, C. J. and Tetteh, K. K. A. (2018) Identification and validation of a novel panel of Plasmodium knowlesi biomarkers of serological exposure. PLoS Neglected Tropical Diseases, 12(6), e0006457. (doi: 10.1371/journal.pntd.0006457) (PMID:29902183) (PMCID:PMC6001954)

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Abstract

Background: Plasmodium knowlesi is the most common cause of malaria in Malaysian Borneo, with reporting limited to clinical cases presenting to health facilities and scarce data on the true extent of transmission. Serological estimations of transmission have been used with other malaria species to garner information about epidemiological patterns. However, there are a distinct lack of suitable serosurveillance tools for this neglected disease. Methodology/Principal findings: Using in silico tools, we designed and expressed four novel P. knowlesi protein products to address the distinct lack of suitable serosurveillance tools: PkSERA3 antigens 1 and 2, PkSSP2/TRAP and PkTSERA2 antigen 1. Antibody prevalence to these antigens was determined by ELISA for three time-points post-treatment from a hospital-based clinical treatment trial in Sabah, East Malaysia (n = 97 individuals; 241 total samples for all time points). Higher responses were observed for the PkSERA3 antigen 2 (67%, 65/97) across all time-points (day 0: 36.9% 34/92; day 7: 63.8% 46/72; day 28: 58.4% 45/77) with significant differences between the clinical cases and controls (n = 55, mean plus 3 SD) (day 0 p<0.0001; day 7 p<0.0001; day 28 p<0.0001). Using boosted regression trees, we developed models to classify P. knowlesi exposure (cross-validated AUC 88.9%; IQR 86.1–91.3%) and identified the most predictive antibody responses. Conclusions/Significance: The PkSERA3 antigen 2 had the highest relative variable importance in all models. Further validation of these antigens is underway to determine the specificity of these tools in the context of multi-species infections at the population level.

Item Type:Articles
Additional Information:Funding: The Wellcome Trust (091924/Z/10/Z) and the Medical Research Council (G1100796; https://www.mrc.ac.uk/). RWM is supported by an MRC Career Development Award (MR/M021157/1) jointly funded by the UK Medical Research Council and UK Department for International Development.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Fornace, Dr Kimberly
Creator Roles:
Fornace, K.Formal analysis, Investigation, Methodology, Resources, Writing – review and editing
Authors: Herman, L. S., Fornace, K., Phelan, J., Grigg, M. J., Anstey, N. M., William, T., Moon, R. W., Blackman, M. J., Drakeley, C. J., and Tetteh, K. K. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Published Online:14 June 2018
Copyright Holders:Copyright © 2018 Herman et al.
First Published:First published in PLoS Neglected Tropical Diseases 12(6): e0006457
Publisher Policy:Reproduced under a Creative Commons License

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