Implications of current therapeutic restrictions for primaquine and tafenoquine in the radical cure of vivax malaria

Abstract

The 8-aminoquinoline antimalarials, the only drugs which prevent relapse of vivax and ovale malaria (radical cure), cause dose-dependent oxidant haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Patients with P. vivax conferred by G6PD deficiency. If tafenoquine is deployed for radical cure, primaquine will still be needed to obtain high population coverage. Better radical cure antimalarial regimens are needed. More than half of the malaria outside of Sub-Saharan Africa is caused by the parasite Plasmodium vivax which is characterised by multiple relapses of malaria from parasites which persist in the liver. The only drugs which prevent these relapses (radical cure) are the 8-aminoquinolines primaquine and tafenoquine, and they both cause haemolytic anaemia in G6PD deficiency, the most common enzymopathy of man. Neither can currently be prescribed in pregnancy or lactation. Tafenoquine is given as a single dose regimen and is a significant advance over primaquine (recommended as a 14 day regimen). However, a greater number of individuals, mostly females, will be ineligible for tafenoquine treatment due to a tighter restriction on the minimum G6PD enzyme activity considered safe for use of the drug. Using enzyme activity data from over 5000 individuals, we estimate the proportions ineligible due to G6PD deficiency as a function of the deficient allele prevalence. Adding this to simple estimates of pregnancy and lactation, we estimate the proportions of populations who cannot receive either tafenoquine or primaquine radical cure. For the elimination of vivax malaria in areas with a high prevalence of G6PD deficiency, then if tafenoquine is deployed primaquine will still be needed, so better regimens should be developed.