Quantifying the contribution of Plasmodium falciparum malaria to febrile illness amongst African children

  1. Ursula Dalrymple  Is a corresponding author
  2. Ewan Cameron
  3. Samir Bhatt
  4. Daniel J Weiss
  5. Sunetra Gupta
  6. Peter W Gething  Is a corresponding author
  1. University of Oxford, United Kingdom

Abstract

Suspected malaria cases in Africa increasingly receive a rapid diagnostic test (RDT) before antimalarials are prescribed. While this ensures efficient use of resources to clear parasites, the underlying cause of the individual's fever remains unknown due to potential coinfection with a non-malarial febrile illness. Widespread use of RDTs does not necessarily prevent over-estimation of clinical malaria cases or sub-optimal case management of febrile patients. We present a new approach that allows inference of the spatiotemporal prevalence of both Plasmodium falciparum malaria-attributable and non-malarial fever in sub-Saharan African children from 2006-2014. We estimate that 35.7% of all self-reported fevers were accompanied by a malaria infection in 2014, but that only 28.0% of those (10.0% of all fevers) were causally attributable to malaria. Most fevers among malaria-positive children are therefore caused by non-malaria illnesses. This refined understanding can help improve interpretation of the burden of febrile illness and shape policy on fever case management.

Data availability

The following previously published data sets were used
    1. DHS Program
    (2006) DHS Program Datasets
    Available upon request from the DHS Program.

Article and author information

Author details

  1. Ursula Dalrymple

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    For correspondence
    ursula.dalrymple@zoo.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6206-3777
  2. Ewan Cameron

    Big Data Institute, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Samir Bhatt

    Big Data Institute, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel J Weiss

    Big Data Institute, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Sunetra Gupta

    Department of Zoology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Peter W Gething

    Big Data Institute, University of Oxford, Oxford, United Kingdom
    For correspondence
    peter.gething@bdi.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Funding

Medical Research Council (Doctoral Training Grant)

  • Ursula Dalrymple

Bill and Melinda Gates Foundation (H5R00640 H5R00690)

  • Ewan Cameron
  • Samir Bhatt
  • Daniel J Weiss
  • Peter W Gething

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

Reviewing Editor

  1. Mark Jit, London School of Hygiene & Tropical Medicine, and Public Health England, United Kingdom

Publication history

  1. Received: June 1, 2017
  2. Accepted: October 12, 2017
  3. Accepted Manuscript published: October 16, 2017 (version 1)
  4. Version of Record published: November 1, 2017 (version 2)
  5. Version of Record updated: May 16, 2018 (version 3)

Copyright

© 2017, Dalrymple 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. Ursula Dalrymple
  2. Ewan Cameron
  3. Samir Bhatt
  4. Daniel J Weiss
  5. Sunetra Gupta
  6. Peter W Gething
(2017)
Quantifying the contribution of Plasmodium falciparum malaria to febrile illness amongst African children
eLife 6:e29198.
https://doi.org/10.7554/eLife.29198

Further reading

    1. Epidemiology and Global Health
    2. Medicine
    Nathan J Cheetham, Milla Kibble ... Claire J Steves
    Research Article

    Background: SARS-CoV-2 antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. Higher levels of SARS-CoV-2 anti-Spike antibodies are known to be associated with increased protection against future SARS-CoV-2 infection. However, variation in antibody levels and risk factors for lower antibody levels following each round of SARS-CoV-2 vaccination have not been explored across a wide range of socio-demographic, SARS-CoV-2 infection and vaccination, and health factors within population-based cohorts.

    Methods: Samples were collected from 9,361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies and tested for SARS-CoV-2 antibodies. Cross-sectional sampling was undertaken jointly in April-May 2021 (TwinsUK, N = 4,256; ALSPAC, N = 4,622), and in TwinsUK only in November 2021-January 2022 (N = 3,575). Variation in antibody levels after first, second, and third SARS-CoV-2 vaccination with health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables were analysed. Using multivariable logistic regression models, we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables.

    Results: Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had 3-fold greater odds of SARS-CoV-2 infection over the next six to nine months (OR = 2.9, 95% CI: 1.4, 6.0), compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK 'Shielded Patient List' had consistently greater odds (2- to 4-fold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations.

    Conclusions: These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies.

    Funding: Antibody testing was funded by UK Health Security Agency. The National Core Studies program is funded by COVID-19 Longitudinal Health and Wellbeing - National Core Study (LHW-NCS) HMT/UKRI/MRC (MC_PC_20030 & MC_PC_20059). Related funding was also provided by the NIHR 606 (CONVALESCENCE grant COV-LT-0009). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC.