Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission

  1. Michael T White  Is a corresponding author
  2. Stephan Karl
  3. Katherine E Battle
  4. Simon I Hay
  5. Ivo Mueller
  6. Azra C Ghani
  1. Imperial College London, United Kingdom
  2. Walter and Eliza Hall Institute, Australia
  3. University of Oxford, United Kingdom

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

  1. Michael T White

    Imperial College London, London, United Kingdom
    For correspondence
    m.white08@imperial.ac.uk
    Competing interests
    No competing interests declared.
  2. Stephan Karl

    Walter and Eliza Hall Institute, Melbourne, Australia
    Competing interests
    No competing interests declared.
  3. Katherine E Battle

    University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  4. Simon I Hay

    University of Oxford, Oxford, United Kingdom
    Competing interests
    Simon I Hay, Reviewing editor, eLife.
  5. Ivo Mueller

    Walter and Eliza Hall Institute, Melbourne, Australia
    Competing interests
    No competing interests declared.
  6. Azra C Ghani

    Imperial College London, London, United Kingdom
    Competing interests
    No competing interests declared.

Reviewing Editor

  1. Mark Jit, London School of Hygiene & Tropical Medicine, and Public Health England, United Kingdom

Publication history

  1. Received: September 10, 2014
  2. Accepted: November 13, 2014
  3. Accepted Manuscript published: November 18, 2014 (version 1)
  4. Version of Record published: December 2, 2014 (version 2)

Copyright

© 2014, White et al.

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.

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  1. Michael T White
  2. Stephan Karl
  3. Katherine E Battle
  4. Simon I Hay
  5. Ivo Mueller
  6. Azra C Ghani
(2014)
Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission
eLife 3:e04692.
https://doi.org/10.7554/eLife.04692
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