Genotypes and phenotypes of G6PD deficiency among Indonesian females across diagnostic thresholds of G6PD activity guiding safe primaquine therapy of latent malaria

Background Plasmodium vivax occurs as a latent infection of liver and a patent infection of red blood cells. Radical cure requires both blood schizontocidal and hypnozoitocidal chemotherapies. The hypnozoitocidal therapies available are primaquine and tafenoquine, 8-aminoquinoline drugs that can provoke threatening acute hemolytic anemia in patients having an X-linked G6PD-deficiency. Heterozygous females may screen as G6PD-normal prior to radical cure and go on to experience hemolytic crisis. Methods & findings This study examined G6PD phenotypes in 1928 female subjects living in malarious Sumba Island in eastern Indonesia to ascertain the prevalence of females vulnerable to diagnostic misclassification as G6PD-normal. All 367 (19%) females having
Author summary Plasmodium vivax causes patent infection of red blood cells and latent infection of the liver. Radical cure for malaria effectively kills parasites in both blood and liver stages. Currently, radical cure for malaria involves either primaquine or tafenoquine, both of which cause acute hemolytic anemia in patients with an inherited defect in G6PD enzymatic activity. G6PD deficiency is an X-linked disorder and it is the most common enzyme deficiency in humans. Heterozygous females having one mutated and one normal gene may screen as G6PD normal in qualitative enzyme activity screening prior to primaquine therapy and be at risk of proceeding to hemolytic crisis. To date, there is no evidence-based G6PD activity cut-off value to distinguish those females who may not safely receive primaquine. This study aimed to inform this cut-off by a large survey of females by quantitative G6PD activity phenotyping along with genotyping of the G6PD gene. Two thousand females residing in a meso-endemic area in eastern Indonesia were screened for G6PD deficiency using qualitative and quantitative tests. Those with