Amplicon-based DNA sequencing to characterize Duffy antigen polymorphisms and analysis of Duffy blood system and glucose-6-phosphate dehydrogenase deficiency in Mauritania

by Albin Fontaine, Oum Kelthoum Mamadou Djigo, Nicolas Gomez, Ali Ould Mohamed Salem Boukhary, Leonardo Basco, Sébastien Briolant

Background

Both Duffy blood antigen expression and G6PD deficiency are known to be associated with ethnic origin. Updates in epidemiological data on the prevalence of polymorphisms in these two human genes are key information for guiding national programs to eliminate Plasmodium vivax malaria.

Methods

Duffy genotypes and their predicted phenotypes were determined in 943 blood samples from Mauritanian patients belonging to different ethnic groups (n = 432 White Moors and n = 511 individuals of black African ancestry) with a known G6PD genotype determined by PCR-restriction fragment length polymorphism in our previous study, using a cost-saving multiplexed barcoding technique that allows simultaneous analysis of a large number of samples and next-generation DNA sequencing (NGS).

Results

Duffy-negative phenotype predicted from Duffy genotype was predominant in individuals with black African ancestry (65–88%), while 16% of white Moors were Duffy-negative. Among 432 samples with interpretable Duffy sequence data from white Moors, 7/356 (2.0%) were Duffy-positive and G6PD A^– deficient; 8/76 (10.5%) were Duffy-negative and G6PD A^– deficient, mostly (n = 6) in heterozygous females. By contrast, among 511 patients of black African ancestry, 13 (13/140, 9.3% including heterozygous females) were Duffy-positive and G6PD A^– deficient; 65 (65/371, 17.5%) were Duffy-negative and G6PD A^– deficient, mostly (n = 44) in heterozygous females.

Conclusion

A large majority of white Moors are Duffy-positive and susceptible to P. vivax infection, but most are eligible for anti-hypnozoite therapy with primaquine at the standard dose. About 15.4% of individuals with black African ancestry were affected by G6PD A^– deficiency, independently of their Duffy receptor status. This population requires G6PD screening before primaquine therapy in rare cases of P. vivax infection. These results provide important clues about the feasibility to implement an efficient anti-hypnozoite treatment in Mauritania and identify priority areas for targeted interventions against P. vivax malaria.