Prevalence and genetic variants of glucose-6-phosphate dehydrogenase in malaria-endemic communities along the Lake Victoria basin, Kenya

Abstract Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common X-linked disorder in malaria-endemic regions, can cause haemolysis following primaquine treatment. Primaquine is vital for eliminating P. vivax , P. ovale hypnozoites, and P. falciparum gametocytes. Despite increasing non- falciparum malaria and artemisinin-resistant P. falciparum in Sub-Saharan Africa, primaquine uptake remains limited due to safety concerns in G6PD-deficient individuals. We assessed G6PD deficiency prevalence and its association with Plasmodium infections among 1661 individuals from five communities around Lake Victoria in Homa Bay County, Kenya. G6PD activity was measured using the Dojindo G6PD Assay Kit-WST, with deficiency defined as < 30% of the adjusted male median activity. Selected samples were genotyped for G202A, A376G, A542T, G680T, and T968C. Associations with Plasmodium infection and clinical attributes were analysed using ordinal logistic regression. Overall G6PD deficiency prevalence was 6.8% ( n = 113): 9.0% (69/765) in males and 4.9% (44/896) in females. G6PD deficiency was primarily explained by the G202A variant (G6PD A-/Asahi). Of 104 G6PD-deficient individuals genotyped, 66 were hemizygous, 26 homozygous, and 7 heterozygous for G6PD A- or Asahi variants. Whole gene sequencing further revealed G6PD Sibari (A634G) in a deficient male. G6PD deficiency did not protect against Plasmodium infection, however microscopic infections were associated with living in communities with higher parasite prevalence, male sex, young age, severe anaemia, and bed net disuse.