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.

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.

Metrics

  • 2,457
    views
  • 529
    downloads
  • 82
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

https://doi.org/10.7554/eLife.04692

Further reading

    1. Epidemiology and Global Health
    2. Genetics and Genomics
    Rashmi Sukumaran, Achuthsankar S Nair, Moinak Banerjee
    Research Article

    Burden of stroke differs by region, which could be attributed to differences in comorbid conditions and ethnicity. Genomewide variation acts as a proxy marker for ethnicity, and comorbid conditions. We present an integrated approach to understand this variation by considering prevalence and mortality rates of stroke and its comorbid risk for 204 countries from 2009 to 2019, and Genome-wide association studies (GWAS) risk variant for all these conditions. Global and regional trend analysis of rates using linear regression, correlation, and proportion analysis, signifies ethnogeographic differences. Interestingly, the comorbid conditions that act as risk drivers for stroke differed by regions, with more of metabolic risk in America and Europe, in contrast to high systolic blood pressure in Asian and African regions. GWAS risk loci of stroke and its comorbid conditions indicate distinct population stratification for each of these conditions, signifying for population-specific risk. Unique and shared genetic risk variants for stroke, and its comorbid and followed up with ethnic-specific variation can help in determining regional risk drivers for stroke. Unique ethnic-specific risk variants and their distinct patterns of linkage disequilibrium further uncover the drivers for phenotypic variation. Therefore, identifying population- and comorbidity-specific risk variants might help in defining the threshold for risk, and aid in developing population-specific prevention strategies for stroke.

    1. Epidemiology and Global Health
    2. Evolutionary Biology
    Renan Maestri, Benoît Perez-Lamarque ... Hélène Morlon
    Research Article

    Several coronaviruses infect humans, with three, including the SARS-CoV2, causing diseases. While coronaviruses are especially prone to induce pandemics, we know little about their evolutionary history, host-to-host transmissions, and biogeography. One of the difficulties lies in dating the origination of the family, a particularly challenging task for RNA viruses in general. Previous cophylogenetic tests of virus-host associations, including in the Coronaviridae family, have suggested a virus-host codiversification history stretching many millions of years. Here, we establish a framework for robustly testing scenarios of ancient origination and codiversification versus recent origination and diversification by host switches. Applied to coronaviruses and their mammalian hosts, our results support a scenario of recent origination of coronaviruses in bats and diversification by host switches, with preferential host switches within mammalian orders. Hotspots of coronavirus diversity, concentrated in East Asia and Europe, are consistent with this scenario of relatively recent origination and localized host switches. Spillovers from bats to other species are rare, but have the highest probability to be towards humans than to any other mammal species, implicating humans as the evolutionary intermediate host. The high host-switching rates within orders, as well as between humans, domesticated mammals, and non-flying wild mammals, indicates the potential for rapid additional spreading of coronaviruses across the world. Our results suggest that the evolutionary history of extant mammalian coronaviruses is recent, and that cases of long-term virus–host codiversification have been largely over-estimated.