Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum
BackgroundPlasmodium 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...
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.1023219/full |
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| author | Angelica F. Tan Angelica F. Tan Sitti Saimah binti Sakam Giri S. Rajahram Giri S. Rajahram Giri S. Rajahram Timothy William Timothy William Mohammad Faruq Abd Rachman Isnadi Sylvia Daim Bridget E. Barber Bridget E. Barber Steven Kho Colin J. Sutherland Nicholas M. Anstey Nicholas M. Anstey Seda Yerlikaya Donelly A. van Schalkwyk Matthew J. Grigg Matthew J. Grigg |
| author_facet | Angelica F. Tan Angelica F. Tan Sitti Saimah binti Sakam Giri S. Rajahram Giri S. Rajahram Giri S. Rajahram Timothy William Timothy William Mohammad Faruq Abd Rachman Isnadi Sylvia Daim Bridget E. Barber Bridget E. Barber Steven Kho Colin J. Sutherland Nicholas M. Anstey Nicholas M. Anstey Seda Yerlikaya Donelly A. van Schalkwyk Matthew J. Grigg Matthew J. Grigg |
| author_sort | Angelica F. Tan |
| collection | DOAJ |
| description | BackgroundPlasmodium 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.MethodsTen 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.ResultsSamples 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.ConclusionSelected 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. |
| first_indexed | 2024-04-13T23:36:24Z |
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| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-13T23:36:24Z |
| publishDate | 2022-10-01 |
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| spelling | doaj.art-9f1b8bbd82f346958e4f90f33cb6ecaa2022-12-22T02:24:43ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-10-011210.3389/fcimb.2022.10232191023219Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparumAngelica F. Tan0Angelica F. Tan1Sitti Saimah binti Sakam2Giri S. Rajahram3Giri S. Rajahram4Giri S. Rajahram5Timothy William6Timothy William7Mohammad Faruq Abd Rachman Isnadi8Sylvia Daim9Bridget E. Barber10Bridget E. Barber11Steven Kho12Colin J. Sutherland13Nicholas M. Anstey14Nicholas M. Anstey15Seda Yerlikaya16Donelly A. van Schalkwyk17Matthew J. Grigg18Matthew J. Grigg19Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, N T, AustraliaInfectious Diseases Society Kota Kinabalu Sabah – Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, MalaysiaInfectious Diseases Society Kota Kinabalu Sabah – Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, MalaysiaInfectious Diseases Society Kota Kinabalu Sabah – Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, MalaysiaClinical Research Centre, Queen Elizabeth Hospital, Ministry of Health, Kota Kinabalu, Sabah, MalaysiaDepartment of Medicine, Queen Elizabeth Hospital II, Kota Kinabalu, Sabah, MalaysiaInfectious Diseases Society Kota Kinabalu Sabah – Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, MalaysiaClinical Research Centre, Queen Elizabeth Hospital, Ministry of Health, Kota Kinabalu, Sabah, MalaysiaFaculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, MalaysiaFaculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Sabah, MalaysiaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, N T, AustraliaClinical Malaria, Queensland Institute of Medical Research (QIMR) Berghofer Medical Research Institute, Brisbane, QLD, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, N T, AustraliaFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, N T, AustraliaInfectious Diseases Society Kota Kinabalu Sabah – Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, MalaysiaMalaria and Fever, Foundation for Innovative New Diagnostics (FIND), Geneva, SwitzerlandFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomGlobal and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, N T, AustraliaInfectious Diseases Society Kota Kinabalu Sabah – Menzies School of Health Research Clinical Research Unit, Kota Kinabalu, Sabah, MalaysiaBackgroundPlasmodium 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.MethodsTen 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.ResultsSamples 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.ConclusionSelected 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.https://www.frontiersin.org/articles/10.3389/fcimb.2022.1023219/fullmalariaPlasmodium knowlesirapid diagnostic testdiagnostic performancepoint-of-careMalaysia |
| spellingShingle | Angelica F. Tan Angelica F. Tan Sitti Saimah binti Sakam Giri S. Rajahram Giri S. Rajahram Giri S. Rajahram Timothy William Timothy William Mohammad Faruq Abd Rachman Isnadi Sylvia Daim Bridget E. Barber Bridget E. Barber Steven Kho Colin J. Sutherland Nicholas M. Anstey Nicholas M. Anstey Seda Yerlikaya Donelly A. van Schalkwyk Matthew J. Grigg Matthew J. Grigg 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 malaria Plasmodium knowlesi rapid diagnostic test diagnostic performance point-of-care Malaysia |
| title | Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum |
| title_full | Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum |
| title_fullStr | Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum |
| title_full_unstemmed | Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum |
| title_short | Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum |
| title_sort | diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase based rapid tests for plasmodium knowlesi and p falciparum |
| topic | malaria Plasmodium knowlesi rapid diagnostic test diagnostic performance point-of-care Malaysia |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.1023219/full |
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