1. Epidemiology and Global Health
  2. Microbiology and Infectious Disease
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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
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Cite this article as: eLife 2021;10:e68812 doi: 10.7554/eLife.68812

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.

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.

Reviewing Editor

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

Publication 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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Further reading

    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease
    Paul Z Chen et al.
    Research Advance Updated

    Background:

    Previously, we conducted a systematic review and analyzed the respiratory kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Chen et al., 2021). How age, sex, and coronavirus disease 2019 (COVID-19) severity interplay to influence the shedding dynamics of SARS-CoV-2, however, remains poorly understood.

    Methods:

    We updated our systematic dataset, collected individual case characteristics, and conducted stratified analyses of SARS-CoV-2 shedding dynamics in the upper (URT) and lower respiratory tract (LRT) across COVID-19 severity, sex, and age groups (aged 0–17 years, 18–59 years, and 60 years or older).

    Results:

    The systematic dataset included 1266 adults and 136 children with COVID-19. Our analyses indicated that high, persistent LRT shedding of SARS-CoV-2 characterized severe COVID-19 in adults. Severe cases tended to show slightly higher URT shedding post-symptom onset, but similar rates of viral clearance, when compared to nonsevere infections. After stratifying for disease severity, sex and age (including child vs. adult) were not predictive of respiratory shedding. The estimated accuracy for using LRT shedding as a prognostic indicator for COVID-19 severity was up to 81%, whereas it was up to 65% for URT shedding.

    Conclusions:

    Virological factors, especially in the LRT, facilitate the pathogenesis of severe COVID-19. Disease severity, rather than sex or age, predicts SARS-CoV-2 kinetics. LRT viral load may prognosticate COVID-19 severity in patients before the timing of deterioration and should do so more accurately than URT viral load.

    Funding:

    Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant, NSERC Senior Industrial Research Chair, and the Toronto COVID-19 Action Fund.

    1. Epidemiology and Global Health
    Audrie Lin et al.
    Research Advance Updated

    Background:

    Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth.

    Methods:

    We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders.

    Results:

    In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score [95% CI 0.05, 0.42; FDR-corrected p-value = 0.01]). TL was not associated with other outcomes.

    Conclusions:

    Consistent with the metabolic telomere attrition hypothesis, our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address ‘emergency states’ with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first 2 years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories.

    Funding:

    Funded by the Bill and Melinda Gates Foundation.

    Clinical trial number:

    NCT01590095