Characterisation ofPlasmodium vivaxlactate dehydrogenase dynamics inP. vivaxinfections

Abstract

Plasmodium vivaxlactate dehydrogenase (PvLDH) is an essential enzyme in the glycolytic pathway ofPlasmodium vivax. It can also be used as a diagnostic biomarker. Quantitation of plasma PvLDH has been used as a measure ofP. vivaxbiomass in clinical studies of uncomplicated and severe vivax malaria. With the increasing importance of PvLDH in studyingP. vivaxdiagnosis and infection, improved characterisation of the dynamics of this biomarker is important. In this study, we developed mathematical models that capture parasite and matrix PvLDH dynamics inex vivoculture and the human host. We estimated the biological parameters usingex vivoandin vivolongitudinal data of parasitemia and PvLDH concentration collected fromP. vivax-infected humans using Bayesian hierarchical inference. We found that theex vivoandin vivoestimates of PvLDH in a parasitized red blood cell differed significantly across the asexual life cycle, within vivoestimates at least ten-fold higher thanex vivoestimates (for example, the median estimate of intraerythrocytic PvLDH mass at the end of the life cycle was 9.4×10−3ngin vivovs. 5.1×10−4ngex vivo). We also estimated theex vivoPvLDH half-life to be 65.3 h (95% credible interval: 60.8—70.7 h), which is approximately three times longer than the median estimate of thein vivoPvLDH half-life, 21.9 h (16.7—29.9 h). Our findings provide an important foundation to further improve quantitative understanding ofP. vivaxbiology and facilitate the development of PvLDH-based diagnostic tools.