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

Herman, LS; Fornace, K; Phelan, J; Grigg, MJ; Anstey, NM; William, T; Moon, RW; Blackman, MJ; Drakeley, CJ and Tetteh, KKA (2018). Identification and validation of a novel panel of Plasmodium knowlesi biomarkers of serological exposure. [Dataset]. PLOS Neglected Tropical Diseases, London, United Kingdom. https://doi.org/10.1371/journal.pntd.0006457
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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.

Keywords

Plasmodium; Sequence alignment; Malaria; Enzyme-linked immunoassays; Antibodies; Antibody response; Antigenic variation; Serology

Item Type Dataset
Resource Type
Resource Type
Resource Description
Dataset
UNSPECIFIED
Description of data capture 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. 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.
Capture method Experiment: Field Intervention
Date 14 June 2018
Geographical area covered (offline during plugin upgrade)
North Latitude
East Longitude
South Latitude
West Longitude
5.99125
116.115
5.95164
116.062
Language(s) of written materials English
Creator(s) Herman, LS; Fornace, K; Phelan, J; Grigg, MJ; Anstey, NM; William, T; Moon, RW; Blackman, MJ; Drakeley, CJ and Tetteh, KKA
LSHTM Faculty/Department Faculty of Infectious and Tropical Diseases > Dept of Disease Control
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection (-2019)
Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology (-2019)
Participating Institutions London School of Hygiene & Tropical Medicine, London, United Kingdom
Funders
Project
Funder
Grant Number
Funder URI
UNSPECIFIED
Wellcome Trust
091924/Z/10/Z; G1100796; MR/M021157/1;
UNSPECIFIED
UNSPECIFIED
Medical Research Council
UNSPECIFIED
UNSPECIFIED
UNSPECIFIED
Department for International Development
UNSPECIFIED
UNSPECIFIED
Date Deposited 20 Jun 2018 15:01
Last Modified 28 Sep 2018 21:20
Publisher PLOS Neglected Tropical Diseases

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