Impact of asymptomatic Plasmodium falciparum infection on the risk of subsequent symptomatic malaria in a longitudinal cohort in Kenya

  1. Kelsey M Sumner
  2. Judith N Mangeni
  3. Andrew A Obala
  4. Elizabeth Freedman
  5. Lucy Abel
  6. Steven R Meshnick
  7. Jessie K Edwards
  8. Brian W Pence
  9. Wendy Prudhomme-O'Meara
  10. Steve M Taylor  Is a corresponding author
  1. UNC Gillings School of Global Public Health, United States
  2. Moi University, Kenya
  3. Duke University Medical Center, United States
  4. Moi Teaching and Referral Hospital, Kenya
  5. Duke University School of Medicine, United States

Abstract

Background:Asymptomatic Plasmodium falciparum infections are common in sub-Saharan Africa, but their effect on subsequent symptomaticity is incompletely understood.

Methods:In a 29-month cohort of 268 people in Western Kenya, we investigated the association between asymptomatic P. falciparum and subsequent symptomatic malaria with frailty Cox models.

Results:Compared to being uninfected, asymptomatic infections were associated with an increased 1-month likelihood of symptomatic malaria [adjusted Hazard Ratio (aHR):2.61, 95%CI:2.05-3.33], and this association was modified by sex, with females [aHR:3.71, 95%CI:2.62-5.24] at higher risk for symptomaticity than males [aHR:1.76, 95%CI:1.24-2.50]. This increased symptomatic malaria risk was observed for asymptomatic infections of all densities and in people of all ages. Long-term risk was attenuated but still present in children under 5 [29-month aHR:1.38, 95%CI:1.05-1.81].

Conclusions:In this high-transmission setting, asymptomatic P. falciparum can be quickly followed by symptoms and may be targeted to reduce the incidence of symptomatic illness.

Funding:This work was supported by the National Institute of Allergy and Infectious Diseases (R21AI126024 to WPO, R01AI146849 to WPO and SMT).

Data availability

Data will be shared under the auspices of the Principal Investigators. Investigators and potential collaborators interested in the datasets will be asked to submit a brief concept note and analysis plan. Requests will be vetted by Drs. O'Meara and Taylor and appropriate datasets will be provided through a password protected secure FTPS link. No personal identifying information will be made available to any investigator. Relevant GPS coordinates would only be provided when 1) the planned analysis cannot reasonably be accomplished without them and 2) the release of the coordinates is approved by the Institutional Review Board. A random error in the latitude and longitude of 50-100 meters will be added to each pair of coordinates to protect individual household identities. General de-identified datasets will be prepared that can accommodate the majority of requests. These will be prepared, with documentation, as the data is cleaned for analysis in order to reduce time and resources required to respond to individual requests. Recipients of study data will be asked to sign a data sharing agreement that specifies what the data may be used for (specific analyses), criteria for acknowledging the source of the data, and the conditions for publication. It will also stipulate that the recipient may not share the data with other investigators. Requests for data use must be made directly to the PI and not through third parties.

Article and author information

Author details

  1. Kelsey M Sumner

    Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Judith N Mangeni

    School of Public Health, Moi University, Eldoret, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  3. Andrew A Obala

    School of Medicine, Moi University, Eldoret, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  4. Elizabeth Freedman

    Medicine, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Lucy Abel

    AMPATH, Moi Teaching and Referral Hospital, Eldoret, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  6. Steven R Meshnick

    Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jessie K Edwards

    Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Brian W Pence

    Epidemiology, UNC Gillings School of Global Public Health, Chapel Hill, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Wendy Prudhomme-O'Meara

    Medicine, Duke University School of Medicine, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Steve M Taylor

    Medicine, Duke University Medical Center, Durham, United States
    For correspondence
    steve.taylor@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2783-0990

Funding

National Institute of Allergy and Infectious Diseases (R21AI126024)

  • Wendy Prudhomme-O'Meara

National Institute of Allergy and Infectious Diseases (R01AI146849)

  • Wendy Prudhomme-O'Meara
  • Steve M Taylor

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

Reviewing Editor

  1. Marcelo U Ferreira, University of São Paulo, Brazil

Ethics

Human subjects: The study was approved by institutional review boards of Moi University (2017/36), Duke University (Pro00082000), and the University of North Carolina at Chapel Hill (19-1273). All participants or guardians provided written informed consent, and those over age 8 provided additional assent.

Version history

  1. Received: March 26, 2021
  2. Accepted: July 20, 2021
  3. Accepted Manuscript published: July 23, 2021 (version 1)
  4. Version of Record published: August 4, 2021 (version 2)

Copyright

© 2021, Sumner 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. Kelsey M Sumner
  2. Judith N Mangeni
  3. Andrew A Obala
  4. Elizabeth Freedman
  5. Lucy Abel
  6. Steven R Meshnick
  7. Jessie K Edwards
  8. Brian W Pence
  9. Wendy Prudhomme-O'Meara
  10. Steve M Taylor
(2021)
Impact of asymptomatic Plasmodium falciparum infection on the risk of subsequent symptomatic malaria in a longitudinal cohort in Kenya
eLife 10:e68812.
https://doi.org/10.7554/eLife.68812

Share this article

https://doi.org/10.7554/eLife.68812

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