1. Epidemiology and Global Health
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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
Research Article
  • Cited 59
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Cite this article as: eLife 2014;3:e04692 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.

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. Further reading

Further reading

    1. Epidemiology and Global Health
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    Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings.

    Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings.

    Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, with low-income settings characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made.

    Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions.

    Funding: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

    1. Epidemiology and Global Health
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    Methods: We investigate these time trends in an extremely large international cohort of 142,540 patients hospitalised with COVID-19. Investigated are: time from symptom onset to hospital admission, probability of ICU/HDU admission, time from hospital admission to ICU/HDU admission, hospital case fatality ratio (hCFR) and total length of hospital stay.

    Results: Time from onset to admission showed a rapid decline during the first months of the pandemic followed by peaks during August/September and December 2020. ICU/HDU admission was more frequent from June to August. The hCFR was lowest from June to August. Raw numbers for overall hospital stay showed little variation, but there is clear decline in time to discharge for ICU/HDU survivors.

    Conclusions: Our results establish that variables of these kinds have limitations when used as outcome measures in a rapidly-evolving situation.

    Funding: This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z] and the Bill and Melinda Gates Foundation [OPP1209135]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.