Protective effect of Mediterranean type glucose-6-phosphate dehydrogenase deficiency against Plasmodium vivax malaria

  1. Ghulam R Awab
  2. Fahima Aaram
  3. Natsuda Jamornthanyawat
  4. Kanokon Suwannasin
  5. Watcharee Pagornrat
  6. James A Watson
  7. Charles J Woodrow
  8. Arjen M Dondorp
  9. Nicholas PJ Day
  10. Mallika Imwong
  11. Nicholas J White  Is a corresponding author
  1. Nangarhar Medical Faculty, Afghanistan
  2. Kabul Medical University, Afghanistan
  3. Mahidol University, Thailand
  4. Mahidol Oxford Tropical Medicine Research Unit, Thailand
  5. Mahidol-Oxford Tropical Medicine Research Unit, Thailand

Abstract

X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. The severe Mediterranean variant (G6PD Med) found across Europe and Asia is thought to confer protection against malaria, but its effect is unclear. We fitted a Bayesian statistical model to observed G6PD Med allele frequencies in 999 Pashtun patients presenting with acute Plasmodium vivax malaria and 1408 population controls. G6PD Med was associated with reductions in symptomatic P. vivax malaria incidence of 76% (95% CI 58-88) in hemizygous males and homozygous females combined, and 55% (95% CI 38-68) in heterozygous females. Unless there is very large population stratification within the Pashtun (confounding these results), the G6PD Med genotype confers a very large and gene dose proportional protective effect against acute vivax malaria. The proportion of patients with vivax malaria at risk of haemolysis following 8-aminoquinoline radical cure is substantially overestimated by studies measuring G6PD deficiency prevalence in healthy subjects.

Data availability

All data used in the analysis are available along with the code which is given in the supplementary materials.

Article and author information

Author details

  1. Ghulam R Awab

    Nangarhar Medical Faculty, Jalalabad, Afghanistan
    Competing interests
    The authors declare that no competing interests exist.
  2. Fahima Aaram

    Medicine, Kabul Medical University, Kabul, Afghanistan
    Competing interests
    The authors declare that no competing interests exist.
  3. Natsuda Jamornthanyawat

    Department of Molecular Tropical Medicine and Genetics, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  4. Kanokon Suwannasin

    Department of Molecular Tropical Medicine and Genetics, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  5. Watcharee Pagornrat

    Department of Molecular Tropical Medicine and Genetics, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  6. James A Watson

    Nuffield Department of Medicine, Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5524-0325
  7. Charles J Woodrow

    Faculty of Medicine, Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  8. Arjen M Dondorp

    Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5190-2395
  9. Nicholas PJ Day

    Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  10. Mallika Imwong

    Department of Molecular Tropical Medicine and Genetics, Mahidol University, Bangkok, Thailand
    Competing interests
    The authors declare that no competing interests exist.
  11. Nicholas J White

    Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    For correspondence
    nickw@tropmedres.ac
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1897-1978

Funding

Wellcome Trust: Principle Fellowship of NJ White (093956/Z/10/Z)

  • Ghulam R Awab

Wellcome Trust: Major Overseas Programme-Thailand Unit Core Grant (093956/Z/10/Z)

  • Kanokon Suwannasin

Wellcome Trust: Training Fellowship (107548Z/15/Z)

  • Ghulam R Awab

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 clinical studies were approved by the Institutional Review Board of the Afghan Public Health Institute, Ministry of Public Health, Afghanistan, the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University, Thailand, and the Oxford Tropical Research Ethics Committee, Oxford University, UK.

Reviewing Editor

  1. Amy Wesolowski, Johns Hopkins Bloomberg School of Public Health, United States

Publication history

  1. Received: August 25, 2020
  2. Accepted: February 3, 2021
  3. Accepted Manuscript published: February 5, 2021 (version 1)
  4. Version of Record published: February 15, 2021 (version 2)

Copyright

© 2021, Awab 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. Ghulam R Awab
  2. Fahima Aaram
  3. Natsuda Jamornthanyawat
  4. Kanokon Suwannasin
  5. Watcharee Pagornrat
  6. James A Watson
  7. Charles J Woodrow
  8. Arjen M Dondorp
  9. Nicholas PJ Day
  10. Mallika Imwong
  11. Nicholas J White
(2021)
Protective effect of Mediterranean type glucose-6-phosphate dehydrogenase deficiency against Plasmodium vivax malaria
eLife 10:e62448.
https://doi.org/10.7554/eLife.62448

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