Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission

Abstract
Article and author information
Metrics

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.

Article and author information

Author details

Michael T White

Imperial College London, London, United Kingdom

For correspondence
m.white08@imperial.ac.uk

Competing interests
No competing interests declared.
Stephan Karl

Walter and Eliza Hall Institute, Melbourne, Australia

Competing interests
No competing interests declared.
Katherine E Battle

University of Oxford, Oxford, United Kingdom

Competing interests
No competing interests declared.
Simon I Hay

University of Oxford, Oxford, United Kingdom

Competing interests
Simon I Hay, Reviewing editor, eLife.
Ivo Mueller

Walter and Eliza Hall Institute, Melbourne, Australia

Competing interests
No competing interests declared.
Azra C Ghani

Imperial College London, London, United Kingdom

Competing interests
No competing interests declared.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.