Abstract
Commercial point-of-care tests remain insufficient for accurately detecting and differentiating low-level malaria infections in regions co-endemic with multiple non-falciparum species, including zoonotic Plasmodium knowlesi (Pk). A 5-plex chemiluminescent assay simultaneously measures pan-Plasmodium lactate dehydrogenase (pLDH), P. falciparum (Pf)-LDH, P. vivax (Pv)-LDH, Pf-histidine-rich protein-2 (HRP2), and C-reactive protein. We assessed its diagnostic performance on whole blood (WB) samples from 102 healthy controls and 306 PCR-confirmed clinical cases of Pf, Pv, Pk, P. malariae (Pm) and P. ovale (Po) mono-infections from Southeast-Asia. We confirm its excellent HRP2-based detection of Pf. Cross-reactivity of Pf-LDH with all non-falciparum species tested was observed (specificity 57.3%). Pv-LDH performance was suboptimal for Pv (93.9% sensitivity and 73.9% specificity). Poor specificity was driven by strong Pk cross-reactivity, with Pv-LDH detecting 93.9% of Pk infections. The pan-LDH-to-Pf-LDH ratio was capable of discerning Pv from Pk, and robustly differentiated Pf from Pm or Po infection, useful in regions with hrp2/3 deletions. We tested the platform’s performance in plasma for the first time, with WB outperforming plasma for all analytes except Pv-LDH for Pk. The platform is a promising tool for WB malaria diagnosis, although further development is warranted to improve its utility in regions co-endemic for multiple non-falciparum species.
Original language | English |
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Article number | 7286 |
Pages (from-to) | 1-9 |
Number of pages | 9 |
Journal | Scientific Reports |
Volume | 12 |
Issue number | 1 |
DOIs | |
Publication status | Published - May 2022 |
Bibliographical note
Funding support from the Australian National Health and Medical Research Council (the Australian Centre of Research Excellence in Malaria Elimination, Program Grant #1,037,304, and Fellowships to SK [Improving Health Outcomes in the Tropical North (HOTNORTH); #1131932], NMA [#1135820] and MJG [#1138860]). MJG is supported by the Australian Centre for International Agricultural Research (Grant #LS2019116). GJD and IKJ are supported by the Bill & Melinda Gates Foundation (Grant # INV1135840). We thank the Director-General, Ministry of Health, Malaysia for permission to publish this paper.Publisher Copyright:
© 2022, The Author(s).