Journal
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2022.1023219
Keywords
malaria; Plasmodium knowlesi; rapid diagnostic test; diagnostic performance; point-of-care; Malaysia; parasite lactate dehydrogenase
Categories
Funding
- Australian Centre of Research Excellence in Malaria Elimination
- National Health and Medical Research Council, Australia [1037304, 1045156, 1042072, 1138860]
- National Institutes of Health, USA [R01AI160457-01, R01AI160457-02]
- Malaysian Ministry of Health [BP00500/117/1002]
- Malaysia Australia Colombo Plan Commemoration (MACC)
- Australian Government Research Training Program (RTP) Scholarship at Charles Darwin University
- Australian Centre for International Agricultural Research, Australian Government [LS-2019-116]
- Bill & Melinda Gates Foundation [OPP1172683]
- Bill and Melinda Gates Foundation [OPP1172683] Funding Source: Bill and Melinda Gates Foundation
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The study evaluated ten rapid diagnostic tests for detection of P. knowlesi, with some tests showing sufficient performance for detecting major human malaria species (including P. knowlesi) in co-endemic areas, particularly for higher parasite counts. However, these tests cannot reliably differentiate non-falciparum malaria.
Background: Plasmodium knowlesi causes zoonotic malaria across Southeast Asia. First-line diagnostic microscopy cannot reliably differentiate P. knowlesi from other human malaria species. Rapid diagnostic tests (RDTs) designed for P. falciparum and P. vivax are used routinely in P. knowlesi co-endemic areas despite potential cross-reactivity for species-specific antibody targets. Methods: Ten RDTs were evaluated: nine to detect clinical P. knowlesi infections from Malaysia, and nine assessing limit of detection (LoD) for P. knowlesi (PkA1-H.1) and P. falciparum (Pf3D7) cultures. Targets included Plasmodium-genus parasite lactate dehydrogenase (pan-pLDH) and P. vivax (Pv)-pLDH. Results: Samples were collected prior to antimalarial treatment from 127 patients with microscopy-positive PCR-confirmed P. knowlesi mono-infections. Median parasitaemia was 788/mu L (IQR 247-5,565/mu L). Pan-pLDH sensitivities ranged from 50.6% (95% CI 39.6-61.5) (SD BIOLINE) to 87.0% (95% CI 75.1-94.6) (First Response (R) and CareStart (TM) PAN) compared to reference PCR. Pv-pLDH RDTs detected P. knowlesi with up to 92.0% (95% CI 84.3-96.7%) sensitivity (Biocredit (TM)). For parasite counts >= 200/mu L, pan-pLDH (Standard Q) and Pv-pLDH RDTs exceeded 95% sensitivity. Specificity of RDTs against 26 PCR-confirmed negative controls was 100%. Sensitivity of six highest performing RDTs were not significantly different when comparing samples taken before and after (median 3 hours) antimalarial treatment. Parasite ring stages were present in 30% of pre-treatment samples, with ring stage proportions (mean 1.9%) demonstrating inverse correlation with test positivity of Biocredit (TM) and two CareStart (TM) RDTs. For cultured P. knowlesi, CareStart (TM) PAN demonstrated the lowest LoD at 25 parasites/mu L; LoDs of other pan-pLDH ranged from 98 to >2000 parasites/mu L. Pv-pLDH LoD for P. knowlesi was 49 parasites/mu L. No false-positive results were observed in either P. falciparum-pLDH or histidine-rich -protein-2 channels. Conclusion: Selected RDTs demonstrate sufficient performance for detection of major human malaria species including P. knowlesi in co-endemic areas where microscopy is not available, particularly for higher parasite counts, although cannot reliably differentiate among non-falciparum malaria.
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