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Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum.
Front Cell Infect Microbiol. 2022; 12:1023219.FC

Abstract

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/µL (IQR 247-5,565/µL). 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® and CareStart™ PAN) compared to reference PCR. Pv-pLDH RDTs detected P. knowlesi with up to 92.0% (95% CI 84.3-96.7%) sensitivity (Biocredit™). For parasite counts ≥200/µL, 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™ and two CareStart™ RDTs.For cultured P. knowlesi, CareStart™ PAN demonstrated the lowest LoD at 25 parasites/µL; LoDs of other pan-pLDH ranged from 98 to >2000 parasites/µL. Pv-pLDH LoD for P. knowlesi was 49 parasites/µL. 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.

Links

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Authors+Show Affiliations

Tan AF
Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, N T, Australia. Infectious Diseases Society Kota Kinabalu Sabah - Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia.
Sakam SSB
Infectious Diseases Society Kota Kinabalu Sabah - Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia.
Rajahram GS
Infectious Diseases Society Kota Kinabalu Sabah - Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia. Clinical Research Centre, Queen Elizabeth Hospital, Ministry of Health, Kota Kinabalu, Sabah, Malaysia. Department of Medicine, Queen Elizabeth Hospital II, Kota Kinabalu, Sabah, Malaysia.
William T
Infectious Diseases Society Kota Kinabalu Sabah - Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia. Clinical Research Centre, Queen Elizabeth Hospital, Ministry of Health, Kota Kinabalu, Sabah, Malaysia.
Abd Rachman Isnadi MF
Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia.
Daim S
Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, Malaysia.
Barber BE
Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, N T, Australia. Clinical Malaria, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Kho S
Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, N T, Australia.
Sutherland CJ
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Anstey NM
Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, N T, Australia. Infectious Diseases Society Kota Kinabalu Sabah - Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia.
Yerlikaya S
Malaria and Fever, Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland.
van Schalkwyk DA
Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Grigg MJ
Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, N T, Australia. Infectious Diseases Society Kota Kinabalu Sabah - Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, Malaysia.

MeSH

AnimalsHumansPlasmodium knowlesiParasitesL-Lactate DehydrogenasePlasmodium vivaxLimit of DetectionAntimalarialsPlasmodium falciparumSensitivity and SpecificityMalaria, FalciparumMalariaMalaria, VivaxDiagnostic Tests, RoutineAntigens, ProtozoanProtozoan Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

36325471

Citation

Tan, Angelica F., et al. "Diagnostic Accuracy and Limit of Detection of Ten Malaria Parasite Lactate Dehydrogenase-based Rapid Tests for Plasmodium Knowlesi and P. Falciparum." Frontiers in Cellular and Infection Microbiology, vol. 12, 2022, p. 1023219.
Tan AF, Sakam SSB, Rajahram GS, et al. Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum. Front Cell Infect Microbiol. 2022;12:1023219.
Tan, A. F., Sakam, S. S. B., Rajahram, G. S., William, T., Abd Rachman Isnadi, M. F., Daim, S., Barber, B. E., Kho, S., Sutherland, C. J., Anstey, N. M., Yerlikaya, S., van Schalkwyk, D. A., & Grigg, M. J. (2022). Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum. Frontiers in Cellular and Infection Microbiology, 12, 1023219. https://doi.org/10.3389/fcimb.2022.1023219
Tan AF, et al. Diagnostic Accuracy and Limit of Detection of Ten Malaria Parasite Lactate Dehydrogenase-based Rapid Tests for Plasmodium Knowlesi and P. Falciparum. Front Cell Infect Microbiol. 2022;12:1023219. PubMed PMID: 36325471.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum. AU - Tan,Angelica F, AU - Sakam,Sitti Saimah Binti, AU - Rajahram,Giri S, AU - William,Timothy, AU - Abd Rachman Isnadi,Mohammad Faruq, AU - Daim,Sylvia, AU - Barber,Bridget E, AU - Kho,Steven, AU - Sutherland,Colin J, AU - Anstey,Nicholas M, AU - Yerlikaya,Seda, AU - van Schalkwyk,Donelly A, AU - Grigg,Matthew J, Y1 - 2022/10/17/ PY - 2022/08/19/received PY - 2022/09/26/accepted PY - 2022/11/3/entrez PY - 2022/11/4/pubmed PY - 2022/11/5/medline KW - Malaysia KW - Plasmodium knowlesi KW - diagnostic performance KW - malaria KW - parasite lactate dehydrogenase KW - point-of-care KW - rapid diagnostic test SP - 1023219 EP - 1023219 JF - Frontiers in cellular and infection microbiology JO - Front Cell Infect Microbiol VL - 12 N2 - 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/µL (IQR 247-5,565/µL). 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® and CareStart™ PAN) compared to reference PCR. Pv-pLDH RDTs detected P. knowlesi with up to 92.0% (95% CI 84.3-96.7%) sensitivity (Biocredit™). For parasite counts ≥200/µL, 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™ and two CareStart™ RDTs.For cultured P. knowlesi, CareStart™ PAN demonstrated the lowest LoD at 25 parasites/µL; LoDs of other pan-pLDH ranged from 98 to >2000 parasites/µL. Pv-pLDH LoD for P. knowlesi was 49 parasites/µL. 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. SN - 2235-2988 UR - https://www.unboundmedicine.com/medline/citation/36325471/Diagnostic_accuracy_and_limit_of_detection_of_ten_malaria_parasite_lactate_dehydrogenase_based_rapid_tests_for_Plasmodium_knowlesi_and_P__falciparum_ DB - PRIME DP - Unbound Medicine ER -