Diagnostic performance of a 5-plex malaria immunoassay in regions co-endemic for Plasmodium falciparum, P. vivax, P. knowlesi, P. malariae and P. ovale

Steven Kho, Nicholas M. Anstey, Bridget E. Barber, Kim Piera, Timothy William, Enny Kenangalem, James S. McCarthy, Ihn Kyung Jang, Gonzalo J. Domingo, Sumudu Britton, Matthew J. Grigg

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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 languageEnglish
Article number7286
Pages (from-to)1-9
Number of pages9
JournalScientific Reports
Issue number1
Publication statusPublished - 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).


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