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Meta-Analysis
. 2021 Feb 5:10:e62448.
doi: 10.7554/eLife.62448.

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

Ghulam R Awab  1   2 , Fahima Aaram  3 , Natsuda Jamornthanyawat  4 , Kanokon Suwannasin  4 , Watcharee Pagornrat  4 , James A Watson  1   5 , Charles J Woodrow  1   5 , Arjen M Dondorp  1   5 , Nicholas Pj Day  1   5 , Mallika Imwong  4 , Nicholas J White  1   5
Affiliations
Meta-Analysis

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

Ghulam R Awab et al. Elife. .

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% credible interval [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.

Keywords: G6PD; Plasmodium vivax; enzymopathy; epidemiology; global health; glucose-6-phosphate dehydrogenase deficiency; malaria; primaquine.

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Conflict of interest statement

GA, FA, NJ, KS, WP, JW, CW, AD, ND, MI, NW No competing interests declared

Figures

Figure 1.
Figure 1.. Locations of the two vivax malaria clinical study sites in Eastern Afghanistan from the present study (red circles), and the approximate locations of the villages in the North-West frontier province of Pakistan where Afghan Pashtun refugees were enrolled in vivax malaria clinical trials and later included in case–control studies (Leslie et al., 2010) (blue circles).
Figure 2.
Figure 2.. Results from the meta-analysis assessing the protective effect of the Mediterranean variant of G6PD deficiency against Plasmodium vivax malaria.
The posterior distributions of 1-α (top: hemi/homozygotes) and 1-β (bottom: heterozygotes) are shown as percentages. These values represent the reduction in prevalence of clinical vivax malaria relative to G6PD normal individuals. The circles show the median estimates, with the 50% credible intervals shown by the thick blue lines and the 95% credible intervals shown by the thin blue lines.
Figure 3.
Figure 3.. Distribution of admission haemoglobin concentrations in P. vivax malaria cases (overall: top row; stratified by G6PD genotype: bottom row).
The top row shows the distribution of haemoglobin concentrations in the first part of the study (left panel, when there was a cut-off at 8 g/dL for inclusion) and in the second part of the study (right panel: after this inclusion criteria was relaxed). The bottom row shows these two distributions stratified by the patients’ G6PD genotypes.
Author response image 1.
Author response image 1.
See this image and copyright information in PMC

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