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评价间日疟原虫乳酸脱氢酶动力学在间日疟原虫感染中的作用。

Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections.

机构信息

School of Mathematics and Statistics, University of Melbourne, Melbourne, VIC, Australia.

Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia.

出版信息

Commun Biol. 2024 Mar 22;7(1):355. doi: 10.1038/s42003-024-05956-6.

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 × 10ng. 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.

摘要

恶性疟原虫乳酸脱氢酶(PvLDH)是恶性疟原虫糖酵解途径中的一种必需酶。它被广泛用作诊断生物标志物和衡量间日疟原虫总虫体生物量的指标。然而,恶性疟原虫乳酸脱氢酶的动态变化仍知之甚少。在这里,我们开发了数学模型,以捕捉寄生虫和基质 PvLDH 在体外培养和人体宿主中的动态变化。我们根据从感染恶性疟原虫的人类中收集的寄生虫血症和 PvLDH 浓度的纵向数据,基于对体内 PvLDH 动态变化的特征的关键生物学参数进行了估计,这些估计是在贝叶斯层次框架中,通过体外数据作为先验知识来提供信息的。我们发现,红细胞内 PvLDH 的体内积累率在入侵后 10-20 小时(晚期环状阶段)达到峰值,红细胞内 PvLDH 质量的中位数估计值在生命周期结束时为 9.4×10ng。我们还发现,体内 PvLDH 半衰期的中位数估计值约为 21.9 小时。我们的研究结果为我们定量理解恶性疟原虫生物学提供了基础,并将有助于改进基于 PvLDH 的诊断工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a49/10959993/72bddc01df22/42003_2024_5956_Fig1_HTML.jpg

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