Spatial distribution of G6PD deficiency variants across malaria-endemic regions

Authors

Rosalind E. Howes, University of OxfordFollow
Mewahyu Dewi, Eijkman-Oxford Clinical Research Unit, Jalan Diponegoro No. 69, Jakarta, Indonesia
Frederic B. Piel, University of Oxford
Wuelton M. Monteiro, Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil
Katherine E. Battle, University of Oxford
Jane P. Messina, University of Oxford
Anavaj Sakuntabhai, Institut Pasteur, Unité de Génétique Fonctionnelle des Maladies Infectieuses, Paris, France
Thomas N. Williams, Kenya Medical Research Institute/ Wellcome Trust Programme, Centre for Geographic Medicine Research-Coast, Kilifi District Hospital, Kilifi, Kenya
J. Kevin Baird, Eijkman-Oxford Clinical Research Unit, Jalan Diponegoro No. 69, Jakarta, IndonesiaFollow
Simon I. Hay, University of Oxford

Date of this Version

2013

Citation

Howes et al. Malaria Journal 2013, 12:418

Comments

U.S. Government Work

Abstract

Background: Primaquine is essential for malaria control and elimination since it is the only available drug preventing multiple clinical attacks by relapses of Plasmodium vivax. It is also the only therapy against the sexual stages of Plasmodium falciparum infectious to mosquitoes, and is thus useful in preventing malaria transmission. However, the difficulties of diagnosing glucose-6-phosphate dehydrogenase deficiency (G6PDd) greatly hinder primaquine’s widespread use, as this common genetic disorder makes patients susceptible to potentially severe and fatal primaquine-induced haemolysis. The risk of such an outcome varies widely among G6PD gene variants.

Methods: A literature review was conducted to identify surveys of G6PD variant frequencies among representative population groups. Informative surveys were assembled into two map series: (1) those showing the relative proportions of the different variants among G6PDd individuals; and (2) those showing allele frequencies of G6PD variants based on population surveys without prior G6PDd screening.

Results: Variants showed conspicuous geographic patterns. A limited repertoire of variants was tested for across sub-Saharan Africa, which nevertheless indicated low genetic heterogeneity predominated by the G6PD A-202A mutation, though other mutations were common in western Africa. The severe G6PD Mediterranean variant was widespread across western Asia. Further east, a sharp shift in variants was identified, with high variant heterogeneity in the populations of China and the Asia-Pacific where no single variant dominated.

Conclusions: G6PD variants exhibited distinctive region-specific distributions with important primaquine policy implications. Relative homogeneity in the Americas, Africa, and western Asia contrasted sharply with the heterogeneity of variants in China, Southeast Asia and Oceania. These findings will inform rational risk assessments for primaquine in developing public health strategies for malaria control and elimination, and support the future development of regionally targeted policies. The major knowledge gaps highlighted here strongly advocate for further investigation of G6PD variant diversity and their primaquine-sensitivity phenotypes.