Diagnostic performance of a 5-plex malaria immunoassay in regions co-endemic for Plasmodium falciparum, P. vivax, P. knowlesi, P. malariae and P. ovale
Abstract 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-P...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-11042-w |
| _version_ | 1818197065757360128 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Steven Kho |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T01:44:03Z |
| format | Article |
| id | doaj.art-f431d93e67034c118708832962c78c62 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-12T01:44:03Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f431d93e67034c118708832962c78c622022-12-22T00:42:38ZengNature PortfolioScientific Reports2045-23222022-05-011211910.1038/s41598-022-11042-wDiagnostic performance of a 5-plex malaria immunoassay in regions co-endemic for Plasmodium falciparum, P. vivax, P. knowlesi, P. malariae and P. ovaleSteven Kho0Nicholas M. Anstey1Bridget E. Barber2Kim Piera3Timothy William4Enny Kenangalem5James S. McCarthy6Ihn Kyung Jang7Gonzalo J. Domingo8Sumudu Britton9Matthew J. Grigg10Menzies School of Health Research and Charles Darwin UniversityMenzies School of Health Research and Charles Darwin UniversityMenzies School of Health Research and Charles Darwin UniversityMenzies School of Health Research and Charles Darwin UniversityClinical Research Centre, Queen Elizabeth HospitalPapuan Health and Community Development FoundationThe Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne HospitalDiagnostic Program, PATHDiagnostic Program, PATHQIMR-Berghofer Medical Research InstituteMenzies School of Health Research and Charles Darwin UniversityAbstract 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.https://doi.org/10.1038/s41598-022-11042-w |
| spellingShingle | 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 Diagnostic performance of a 5-plex malaria immunoassay in regions co-endemic for Plasmodium falciparum, P. vivax, P. knowlesi, P. malariae and P. ovale Scientific Reports |
| title | Diagnostic performance of a 5-plex malaria immunoassay in regions co-endemic for Plasmodium falciparum, P. vivax, P. knowlesi, P. malariae and P. ovale |
| title_full | Diagnostic performance of a 5-plex malaria immunoassay in regions co-endemic for Plasmodium falciparum, P. vivax, P. knowlesi, P. malariae and P. ovale |
| title_fullStr | Diagnostic performance of a 5-plex malaria immunoassay in regions co-endemic for Plasmodium falciparum, P. vivax, P. knowlesi, P. malariae and P. ovale |
| title_full_unstemmed | Diagnostic performance of a 5-plex malaria immunoassay in regions co-endemic for Plasmodium falciparum, P. vivax, P. knowlesi, P. malariae and P. ovale |
| title_short | Diagnostic performance of a 5-plex malaria immunoassay in regions co-endemic for Plasmodium falciparum, P. vivax, P. knowlesi, P. malariae and P. ovale |
| title_sort | diagnostic performance of a 5 plex malaria immunoassay in regions co endemic for plasmodium falciparum p vivax p knowlesi p malariae and p ovale |
| url | https://doi.org/10.1038/s41598-022-11042-w |
| work_keys_str_mv | AT stevenkho diagnosticperformanceofa5plexmalariaimmunoassayinregionscoendemicforplasmodiumfalciparumpvivaxpknowlesipmalariaeandpovale AT nicholasmanstey diagnosticperformanceofa5plexmalariaimmunoassayinregionscoendemicforplasmodiumfalciparumpvivaxpknowlesipmalariaeandpovale AT bridgetebarber diagnosticperformanceofa5plexmalariaimmunoassayinregionscoendemicforplasmodiumfalciparumpvivaxpknowlesipmalariaeandpovale AT kimpiera diagnosticperformanceofa5plexmalariaimmunoassayinregionscoendemicforplasmodiumfalciparumpvivaxpknowlesipmalariaeandpovale AT timothywilliam diagnosticperformanceofa5plexmalariaimmunoassayinregionscoendemicforplasmodiumfalciparumpvivaxpknowlesipmalariaeandpovale AT ennykenangalem diagnosticperformanceofa5plexmalariaimmunoassayinregionscoendemicforplasmodiumfalciparumpvivaxpknowlesipmalariaeandpovale AT jamessmccarthy diagnosticperformanceofa5plexmalariaimmunoassayinregionscoendemicforplasmodiumfalciparumpvivaxpknowlesipmalariaeandpovale AT ihnkyungjang diagnosticperformanceofa5plexmalariaimmunoassayinregionscoendemicforplasmodiumfalciparumpvivaxpknowlesipmalariaeandpovale AT gonzalojdomingo diagnosticperformanceofa5plexmalariaimmunoassayinregionscoendemicforplasmodiumfalciparumpvivaxpknowlesipmalariaeandpovale AT sumudubritton diagnosticperformanceofa5plexmalariaimmunoassayinregionscoendemicforplasmodiumfalciparumpvivaxpknowlesipmalariaeandpovale AT matthewjgrigg diagnosticperformanceofa5plexmalariaimmunoassayinregionscoendemicforplasmodiumfalciparumpvivaxpknowlesipmalariaeandpovale |