Abstract
The most common form of malaria outside Africa, Plasmodium vivax, is more difficult to control than P. falciparum because of the latent liver hypnozoite stage, which causes multiple relapses and provides an infectious reservoir. The African (A-) G6PD (glucose-6-phosphate dehydrogenase) deficiency confers partial protection against severe P. falciparum. Recent evidence suggests that the deficiency also confers protection against P. vivax, which could explain its wide geographical distribution in human populations. The deficiency has a potentially serious interaction with antirelapse therapies (8-aminoquinolines such as primaquine). If the level of protection was sufficient, antirelapse therapy could become more widely available. We therefore tested the hypothesis that G6PD deficiency is protective against vivax malaria infection. A case-control study design was used amongst Afghan refugees in Pakistan. The frequency of phenotypic and genotypic G6PD deficiency in individuals with vivax malaria was compared against controls who had not had malaria in the previous two years. Phenotypic G6PD deficiency was less common amongst cases than controls (cases: 4/372 [1.1%] versus controls 42/743 [5.7%]; adjusted odds ratio [AOR] 0.18 [95% confidence interval (CI) 0.06-0.52], p = 0.001). Genetic analysis demonstrated that the G6PD deficiency allele identified (Mediterranean type) was associated with protection in hemizygous deficient males (AOR = 0.12 [95% CI 0.02-0.92], p = 0.041). The deficiency was also protective in females carrying the deficiency gene as heterozygotes or homozygotes (pooled AOR = 0.37 [95% CI 0.15-0.94], p = 0.037). G6PD deficiency (Mediterranean type) conferred significant protection against vivax malaria infection in this population whether measured by phenotype or genotype, indicating a possible evolutionary role for vivax malaria in the selective retention of the G6PD deficiency trait in human populations. Further work is required on the genotypic protection associated with other types of G6PD deficiency and on developing simple point-of-care technologies to detect it before administering antirelapse therapy.
Highlights
The majority of malaria outside sub-Saharan Africa is caused by Plasmodium vivax, which causes up to 390 million clinical cases a year amongst a population at risk of approximately 2.6 billion [1,2]
Further work is required on the genotypic protection associated with other types of Glucose-6-phosphate dehydrogenase (G6PD) deficiency and on developing simple point-of-care technologies to detect it before administering antirelapse therapy
Using a case-control design, we examined the association of G6PD deficiency with vivax malaria, retrospectively, over 2 years of observation
Summary
The majority of malaria outside sub-Saharan Africa is caused by Plasmodium vivax, which causes up to 390 million clinical cases a year amongst a population at risk of approximately 2.6 billion [1,2]. Its wide geographical distribution is due, in part, to its ability to undergo development (sporogony) in mosquitoes at a lower temperature than P. falciparum and to its formation of a latent liver stage (the hypnozoite), which initiates secondary blood-stage infections [3]. These characteristics make vivax malaria significantly more difficult to control or eliminate than falciparum malaria. The most common form of malaria outside Africa, Plasmodium vivax, is more difficult to control than P. falciparum because of the latent liver hypnozoite stage, which causes multiple relapses and provides an infectious reservoir. Hypnozoites can cause a relapse months after the initial bout of malaria and make P. vivax malaria harder to control than P. faciparum malaria
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