A simulation model of the within-host dynamics of Plasmodium vivax infection

Abstract

Background: The benign reputation of Plasmodium vivax is at odds with the burden and severity of the disease. This reputation, combined with restricted in vitro techniques, has slowed efforts to gain an understanding of the parasite biology and interaction with its human host.

Methods: A simulation model of the within-host dynamics of P. vivax infection is described, incorporating distinctive characteristics of the parasite such as the preferential invasion of reticulocytes and hypnozoite production. The developed model is fitted using digitized time-series' from historic neurosyphilis studies, and subsequently validated against summary statistics from a larger study of the same population. The Chesson relapse pattern was used to demonstrate the impact of released hypnozoites.

Results: The typical pattern for dynamics of the parasite population is a rapid exponential increase in the first 10 days, followed by a gradual decline. Gametocyte counts follow a similar trend, but are approximately two orders of magnitude lower. The model predicts that, on average, an infected naïve host in the absence of treatment becomes infectious 7.9 days post patency and is infectious for a mean of 34.4 days. In the absence of treatment, the effect of hypnozoite release was not apparent as newly released parasites were obscured by the existing infection.

Conclusions: The results from the model provides useful insights into the dynamics of P. vivax infection in human hosts, in particular the timing of host infectiousness and the role of the hypnozoite in perpetuating infection.

Figure 1

Example time course of a modelled infection. The infection commences with the release of 10,000 merozoites on Day 0. Subsequent changes in log(parasite) (solid line), log(gametocyte) (dotted line) and host RBC relative abundance (dashed line) are illustrated in the top-left panel. The lower left panel shows the ratio of parasite burden to fever threshold. Histograms to the right show the age profile of the host RBC population (and thus the impact of preferential invasion on the RBC age profile) at three points (Day 20, 40 and 60) during the infection.

Figure 2

95% confidence intervals for simulated P. vivax log ( parasitaemia) produced by the fitted model. Dotted lines represent the six digitized time series (drawn from McKenzie et. al. [21]) used to fit the model.

Figure 3

Model demonstration of hypnozoite-mediated relapse following chemotherapy intervention. The initial infection is cleared by treatment on day 20 prior to relapse on day 25.