Modelling the drivers of the spread of Plasmodium falciparum hrp2 gene deletions in sub-Saharan Africa

  1. Oliver John Watson  Is a corresponding author
  2. Hannah C Slater
  3. Robert Verity
  4. Jonathan B Parr
  5. Melchior K Mwandagalirwa
  6. Antoinette Tshefu
  7. Steven R Meshnick
  8. Azra C Ghani
  1. Imperial College London, United Kingdom
  2. University of North Carolina, United States
  3. University of Kinshasa, Democratic Republic of the Congo

Abstract

Rapid diagnostic tests (RDTs) have transformed malaria diagnosis. The most prevalent P. falciparum RDTs detect histidine-rich protein 2 (PfHRP2). However, pfhrp2 gene deletions yielding false-negative RDTs, first reported in South America in 2010, have been confirmed in Africa and Asia. We developed a mathematical model to explore the potential for RDT-led diagnosis to drive selection of pfhrp2-deleted parasites. Low malaria prevalence and high frequencies of people seeking treatment resulted in the greatest selection pressure. Calibrating our model against confirmed pfhrp2-deletions in the Democratic Republic of Congo, we estimate a starting frequency of 6% pfhrp2-deletion prior to RDT introduction. Furthermore, the patterns observed necessitate a degree of selection driven by the introduction of PfHRP2-based RDT-guided treatment. Combining this with parasite prevalence and treatment coverage estimates, we map the model-predicted spread of pfhrp2-deletion, and identify the geographic regions in which surveillance for pfhrp2-deletion should be prioritised.

Data availability

The following previously published data sets were used

Article and author information

Author details

  1. Oliver John Watson

    Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
    For correspondence
    o.watson15@imperial.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2374-0741
  2. Hannah C Slater

    Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Robert Verity

    Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Jonathan B Parr

    Division of Infectious Diseases, University of North Carolina, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Melchior K Mwandagalirwa

    School of Public Health, University of Kinshasa, Kinshasa, Democratic Republic of the Congo
    Competing interests
    The authors declare that no competing interests exist.
  6. Antoinette Tshefu

    School of Public Health, University of Kinshasa, Kinshasa, Democratic Republic of the Congo
    Competing interests
    The authors declare that no competing interests exist.
  7. Steven R Meshnick

    Division of Infectious Diseases, University of North Carolina, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Azra C Ghani

    MRC Center for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Funding

Wellcome (109312/Z/15/Z)

  • Oliver John Watson

National Institute of Allergy and Infectious Diseases (5R01AI107949)

  • Steven R Meshnick

Imperial College London

  • Hannah C Slater

Medical Research Council (MR/N01507X/1)

  • Robert Verity

Department for International Development

  • Azra C Ghani

National Institute of Allergy and Infectious Diseases (5T32AI007151)

  • Jonathan B Parr

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2017, Watson 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. Oliver John Watson
  2. Hannah C Slater
  3. Robert Verity
  4. Jonathan B Parr
  5. Melchior K Mwandagalirwa
  6. Antoinette Tshefu
  7. Steven R Meshnick
  8. Azra C Ghani
(2017)
Modelling the drivers of the spread of Plasmodium falciparum hrp2 gene deletions in sub-Saharan Africa
eLife 6:e25008.
https://doi.org/10.7554/eLife.25008

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https://doi.org/10.7554/eLife.25008