Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections
Abstract Plasmodium vivax lactate dehydrogenase (PvLDH) is an essential enzyme in the glycolytic pathway of P. vivax. It is widely used as a diagnostic biomarker and a measure of total-body parasite biomass in vivax malaria. However, the dynamics of PvLDH remains poorly understood. Here, we develope...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-05956-6 |
| _version_ | 1797247095591141376 |
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| author | Pengxing Cao Steven Kho Matthew J. Grigg Bridget E. Barber Kim A. Piera Timothy William Jeanne R. Poespoprodjo Ihn Kyung Jang Julie A. Simpson James M. McCaw Nicholas M. Anstey James S. McCarthy Sumudu Britton |
| author_facet | Pengxing Cao Steven Kho Matthew J. Grigg Bridget E. Barber Kim A. Piera Timothy William Jeanne R. Poespoprodjo Ihn Kyung Jang Julie A. Simpson James M. McCaw Nicholas M. Anstey James S. McCarthy Sumudu Britton |
| author_sort | Pengxing Cao |
| collection | DOAJ |
| description | Abstract Plasmodium vivax lactate dehydrogenase (PvLDH) is an essential enzyme in the glycolytic pathway of P. vivax. It is widely used as a diagnostic biomarker and a measure of total-body parasite biomass in vivax malaria. However, the dynamics of PvLDH remains poorly understood. Here, we developed mathematical models that capture parasite and matrix PvLDH dynamics in ex vivo culture and the human host. We estimated key biological parameters characterising in vivo PvLDH dynamics based on longitudinal data of parasitemia and PvLDH concentration collected from P. vivax-infected humans, with the estimates informed by the ex vivo data as prior knowledge in a Bayesian hierarchical framework. We found that the in vivo accumulation rate of intraerythrocytic PvLDH peaks at 10–20 h post-invasion (late ring stage) with a median estimate of intraerythrocytic PvLDH mass at the end of the life cycle to be 9.4 × 10−3ng. We also found that the median estimate of in vivo PvLDH half-life was approximately 21.9 h. Our findings provide a foundation with which to advance our quantitative understanding of P. vivax biology and will facilitate the improvement of PvLDH-based diagnostic tools. |
| first_indexed | 2024-04-24T19:53:15Z |
| format | Article |
| id | doaj.art-d48ba3507e1249c79abee4305c434258 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-04-24T19:53:15Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-d48ba3507e1249c79abee4305c4342582024-03-24T12:29:26ZengNature PortfolioCommunications Biology2399-36422024-03-017111110.1038/s42003-024-05956-6Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infectionsPengxing Cao0Steven Kho1Matthew J. Grigg2Bridget E. Barber3Kim A. Piera4Timothy William5Jeanne R. Poespoprodjo6Ihn Kyung Jang7Julie A. Simpson8James M. McCaw9Nicholas M. Anstey10James S. McCarthy11Sumudu Britton12School of Mathematics and Statistics, University of MelbourneGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin UniversityGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin UniversityQIMR Berghofer Medical Research InstituteGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin UniversityGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin UniversityPapuan Community Health and Development FoundationDiagnostics Program, PATHCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of MelbourneSchool of Mathematics and Statistics, University of MelbourneGlobal and Tropical Health Division, Menzies School of Health Research and Charles Darwin UniversityQIMR Berghofer Medical Research InstituteQIMR Berghofer Medical Research InstituteAbstract Plasmodium vivax lactate dehydrogenase (PvLDH) is an essential enzyme in the glycolytic pathway of P. vivax. It is widely used as a diagnostic biomarker and a measure of total-body parasite biomass in vivax malaria. However, the dynamics of PvLDH remains poorly understood. Here, we developed mathematical models that capture parasite and matrix PvLDH dynamics in ex vivo culture and the human host. We estimated key biological parameters characterising in vivo PvLDH dynamics based on longitudinal data of parasitemia and PvLDH concentration collected from P. vivax-infected humans, with the estimates informed by the ex vivo data as prior knowledge in a Bayesian hierarchical framework. We found that the in vivo accumulation rate of intraerythrocytic PvLDH peaks at 10–20 h post-invasion (late ring stage) with a median estimate of intraerythrocytic PvLDH mass at the end of the life cycle to be 9.4 × 10−3ng. We also found that the median estimate of in vivo PvLDH half-life was approximately 21.9 h. Our findings provide a foundation with which to advance our quantitative understanding of P. vivax biology and will facilitate the improvement of PvLDH-based diagnostic tools.https://doi.org/10.1038/s42003-024-05956-6 |
| spellingShingle | Pengxing Cao Steven Kho Matthew J. Grigg Bridget E. Barber Kim A. Piera Timothy William Jeanne R. Poespoprodjo Ihn Kyung Jang Julie A. Simpson James M. McCaw Nicholas M. Anstey James S. McCarthy Sumudu Britton Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections Communications Biology |
| title | Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections |
| title_full | Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections |
| title_fullStr | Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections |
| title_full_unstemmed | Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections |
| title_short | Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections |
| title_sort | characterisation of plasmodium vivax lactate dehydrogenase dynamics in p vivax infections |
| url | https://doi.org/10.1038/s42003-024-05956-6 |
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