Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission.

Michael T White,Ivo Mueller,Stephan Karl,Azra C Ghani,Katherine E Battle,Simon I Hay

doi:10.7554/elife.04692

Abstract

Plasmodium vivax relapse infections occur following activation of latent liver-stages parasites (hypnozoites) causing new blood-stage infections weeks to months after the initial infection. We develop a within-host mathematical model of liver-stage hypnozoites, and validate it against data from tropical strains of P. vivax. The within-host model is embedded in a P. vivax transmission model to demonstrate the build-up of the hypnozoite reservoir following new infections and its depletion through hypnozoite activation and death. The hypnozoite reservoir is predicted to be over-dispersed with many individuals having few or no hypnozoites, and some having intensely infected livers. Individuals with more hypnozoites are predicted to experience more relapses and contribute more to onwards P. vivax transmission. Incorporating hypnozoite killing drugs such as primaquine into first-line treatment regimens is predicted to cause substantial reductions in P. vivax transmission as individuals with the most hypnozoites are more likely to relapse and be targeted for treatment.

Highlights

The study of the transmission dynamics of vector-borne diseases such as Plasmodium falciparum malaria has a rich history, with a theoretical foundation based on the Ross-Macdonald models, a class of mathematical models describing the transmission of a pathogen between human and vector hosts
Relapse infections arising from the activation of hypnozoites in the human liver have important consequences for the transmission dynamics of P. vivax
Relapses can be incorporated into Ross-Macdonald models of malaria transmission through the addition of a state to represent the hypnozoite reservoir (Roy et al, 2013), or as demonstrated here, through consideration of the number of hypnozoites in the liver

Summary

Introduction

The study of the transmission dynamics of vector-borne diseases such as Plasmodium falciparum malaria has a rich history, with a theoretical foundation based on the Ross-Macdonald models (malERA Consultative Group on Modeling, 2011; Smith et al, 2012; Reiner et al, 2013; Smith et al, 2014), a class of mathematical models describing the transmission of a pathogen between human and vector hosts. In contrast to the extensive theory of the mathematical epidemiology of P. falciparum malaria (Smith et al, 2012), P. vivax malaria has been comparatively neglected. This is in spite of P. vivax being the geographically most widely distributed species of malaria in the world, causing in the region of 80–300 million clinical episodes every year (Mueller et al, 2009a; Gething et al, 2012).

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