Global perspectives on CYP2D6 associations with primaquine metabolism and Plasmodium vivax radical cure

Abstract

Clinical trial and individual patient treatment outcomes have produced accumulating evidence that effective primaquine (PQ) treatment of Plasmodium vivax and P. ovale liver stage hypnozoites is associated with genetic variation in the human cytochrome P450 gene, CYP2D6. Successful PQ treatment of individual and population-wide infections by the Plasmodium species that generate these dormant liver stage forms is likely to be necessary to reach elimination of malaria caused by these parasites globally. Optimizing safe and effective PQ treatment will require coordination of efforts between the malaria and pharmacogenomics research communities.

Association of CYP2C19, CYP2D6 and CYP3A4 Genetic Variants on Primaquine Hemolysis in G6PD-Deficient Patients

“…The antimalarials PQ and TQ are effective drugs that eliminate the hepatic stages of P. vivax and prevent relapses. However, this class of 8-aminoquinolines can cause hemolysis in individuals with low G6PD enzyme activity, which presents an obstacle to the global implementation of drug delivery against vivax malaria [ 29 , 30 ]. The prevalence of G6PDd in the male population has been reported in several studies from around the world, and also in the Amazon region, with a frequency of 4.5% to 10% [ 14 , 16 , 31 ].…”