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.
All data used in the analysis are available along with the code which is given in the supplementary materials.
- Ghulam R Awab
- Kanokon Suwannasin
- Ghulam R Awab
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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.
- Amy Wesolowski, Johns Hopkins Bloomberg School of Public Health, United States
© 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.