Diagnostic Characteristics of Lactate Dehydrogenase on a Multiplex Assay for Malaria Detection Including the Zoonotic Parasite Plasmodium knowlesi

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  • 1 PATH, Seattle, Washington;
  • | 2 University of Georgia, Athens, Georgia;
  • | 3 London School of Hygiene and Tropical Medicine, London, United Kingdom

Plasmodium lactate dehydrogenase (pLDH) is a common target in malaria rapid diagnostic tests (RDTs). These commercial antibody capture assays target either Plasmodium falciparum–specific pLDH (PfLDH), P. vivax–specific pLDH (PvLDH), or a conserved epitope in all human malaria pLDH (PanLDH). However, there are no assays specifically targeting P. ovale, P. malariae or zoonotic parasites such as P. knowlesi and P. cynomolgi. A malaria multiplex array, carrying the specific antibody spots for PfLDH, PvLDH, and PanLDH has been previously developed. This study aimed to assess potential cross-reactivity between pLDH from various Plasmodium species and this array. We tested recombinant pLDH proteins, clinical samples for P. vivax, P. falciparum, P. ovale curtisi, and P. malariae; and in vitro cultured P. knowlesi and P. cynomolgi. P. ovale-specific pLDH (PoLDH) and P. malariae-specific pLDH (PmLDH) cross-reacted with the PfLDH and PanLDH spots. Plasmodium Knowlesi-specific pLDH (PkLDH) and P. cynomolgi-specific pLDH (PcLDH) cross-reacted with the PvLDH spot, but only PkLDH was recognized by the PanLDH spot. Plasmodium ovale and P. malariae can be differentiated from P. falciparum by the concentration ratios of PanLDH/PfLDH, which had mean (range) values of 4.56 (4.07–5.16) and 4.56 (3.43–6.54), respectively, whereas P. falciparum had a lower ratio of 1.12 (0.56–2.61). Plasmodium knowlesi had a similar PanLDH/PvLDH ratio value, with P. vivax having a mean value of 2.24 (1.37–2.79). The cross-reactivity pattern of pLDH can be a useful predictor to differentiate certain Plasmodium species. Cross-reactivity of the pLDH bands in RDTs requires further investigation.

Author Notes

Address correspondence to Ihn Kyung Jang, PATH, 2201 Westlake Ave, Seattle, WA 98121. E-mail: ikjang@path.org.

Financial support: This work was supported in whole by the Bill & Melinda Gates Foundation [Grant number OPP1135840]. Under the grant conditions of the Gate Foundation, a Creative Commons Attribution 4.0 Generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission. RWM is supported by a UK Research and Innovation27 Medical Research Council (MRC) Career Development Award (MR/M021157/1) jointly funded by the UKRI MRC and UK Department for International Development.

Authors’ addresses: Becky Barney, Miguel Velasco, Andrew Rashid, Gonzalo Domingo, and Ihn Kyung Jang, PATH, Seattle, WA, E-mails: rbarney@path.org, mvelasco@path.org, arashid@path.org, gdomingo@path.org, and ikjang@path.org. Caitlin Cooper and Dennis Kyle, University of Georgia, Athens, GA, E-mails: cooper13@uga.edu and dennis.kyle@uga.edu. Robert Moon, London School of Hygiene and Tropical Medicine, Bloomsbury, London, United Kingdom, E-mail: rob.moon@lshtm.ac.uk.