Single low-dose primaquine efficacy and safety for treatment of uncomplicated Plasmodium falciparum malaria based on cytochrome P450 2D6 activity in Bagamoyo district, Tanzania

The World Health Organization (WHO) has now recommended addition of a 0.25 mg/kg single-dose primaquine (PQ) to standard artemisinin-based combination therapy (ACT) for elimination of Plasmodium falciparum malaria in low transmission-settings and for containment in areas threatened by artemisinin resistance. The dose has shown to be safe even in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, and is efficacious for clearance of P. falciparum gametocytes. However, some individuals with normal G6PD status have developed AEs including acute hemolysis following treatment with this single low-dose PQ. Furthermore, a failure rate of =5 has also been reported in gametocyte clearance and transmission blocking after treatment with even high doses of PQ suggesting involvement of other factors in determining PQ safety and efficacy. Due to these safety concerns most of the malaria endemic sub-Saharan African countries have failed to adopt the PQ recommendation. However, PQ metabolism depends on a highly polymorphic cytochrome P450 (CYP) 2D6 isoenzyme, which probably compromises the drug’s safety and efficacy, particularly in individuals with reduced isoenzyme activity. Nonetheless, there is no enough information regarding the effect of CYP2D6 isoenzyme polymorphism on PQ safety and its efficacy in sterilizing mature P. falciparum gametocytes.

EDCTP Grants

Drug-based Strategies

Aug 2018 — Jan 2021

$173,344

Tanzania