Glucose-6-phosphate dehydrogenase (G6PD) deficiency in Ethiopia: absence of common African and Mediterranean allelic variants in a nationwide study

Abstract

Background: Building on the declining trend of malaria in Ethiopia, the Federal Ministry of Health aims to eliminate malaria by 2030. As Plasmodium falciparum and Plasmodium vivax are co-endemic in Ethiopia, the use of primaquine is indicated for both transmission interruption and radical cure, respectively. However, the limited knowledge of the local prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and its associated variants has hindered the use of primaquine.

Methods: Some 11,138 dried blood spot (DBS) samples were collected in 2011 as part of a national, household Malaria Indicator Survey, a multi-stage nationally representative survey of all malaria-endemic areas of Ethiopia. A randomly selected sub-set of 1414 DBS samples was successfully genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Considering the geographical position and ethnic mix of the country, three common variants: G6PD*A (A376G), G6PD*A- (G202A) and Mediterranean (C563T) were investigated.

Results: Of the 1998 randomly selected individuals, 1429 (71.5%) DBS samples were genotyped and merged to the database, of which 53.5% were from females. G6PD*A (A376G) was the only genotype detected. No sample was positive for either G6PD*A- (G202A) or Mediterranean (C563T) variants. The prevalence of G6PD*A (A376G) was 8.9% [95% confidence interval (CI) 6.7-11.2] ranging from 12.2% in the Southern Nations, Nationalities and Peoples' (95% CI 5.7-18.7) to none in Dire Dawa/Harari Region.

Conclusion: The common G6PD*A- (G202A) or Mediterranean (C563T) variants were not observed in this nationwide study. The observed G6PD*A (A376G) mutation has little or no clinical significance. These findings supported the adoption of primaquine for P. falciparum transmission interruption and radical cure of P. vivax in Ethiopia. As the presence of other clinically important, less common variants cannot be ruled out, the implementation of radical cure will be accompanied by active haematological and adverse events monitoring in Ethiopia.

Keywords: Ethiopia; G6PD deficiency; Malaria; Primaquine.

Fig. 1

Picture of gel electrophoresis result showing G6PD*A (A376G) mutation. Lane 1 indicates a molecular ladder of 50 bp. Arrows indicate the site for mutation. a Lane A4 and A13 show partial digestion, cut size 308 (undigested), 183 and 125 bp. b Lane B11 show full digestion, cut size 183 and 125 bp

Fig. 2

Spatial distribution of study samples in Ethiopia. a Distribution of samples selected for G6PD genotyping (n = 1947; 51 samples missing GPS coordinates). b Spatial distribution of G6PD*A mutations (n = 130). Darker color depicts higher altitude and lighter color lower altitude. Areas above 2500 m were considered unsuitable for malaria transmission and were not included in the sampling frame. Each dot represents a household where a DBS was collected