A New Primaquine Analogue, Tafenoquine (WR 238605), for Prophylaxis againstPlasmodium falciparumMalaria

Abstract

We tested tafenoquine (WR 238605), a new long-acting 8-aminoquinoline, for its ability to prevent malaria in an area that is holoendemic for Plasmodium falciparum. In a double-blinded, placebo-controlled, randomized clinical trial in western Kenya, adult volunteers received a treatment course of 250 mg halofantrine per day for 3 days, to effect clearance of preexisting parasites. The volunteers were then assigned to 1 of 4 drug regimens: placebo throughout; 3 days of 400 mg (base) of tafenoquine per day, followed by placebo weekly; 3 days of 200 mg of tafenoquine per day, followed by 200 mg per week; and 3 days of 400 mg of tafenoquine per day, followed by 400 mg per week. Prophylaxis was continued for up to 13 weeks. Of the evaluable subjects (223 of 249 randomized subjects), volunteers who received 400 mg tafenoquine for only 3 days had a protective efficacy of 68% (95% confidence interval [CI], 53%-79%), as compared with placebo recipients; those who received 200 mg per day for 3 days followed by 200 mg per week had a protective efficacy of 86% (95% CI, 73%-93%); and those who received 400 mg for 3 days followed by 400 mg per week had a protective efficacy of 89% (95% CI, 77%-95%). A similar number of volunteers in the 4 treatment groups reported adverse events. Prophylactic regimens of 200 mg or 400 mg of tafenoquine, taken weekly for < or =13 weeks, are highly efficacious in preventing falciparum malaria and are well tolerated.

Evaluation of a Rapid Qualitative Enzyme Chromatographic Test for Glucose-6-Phosphate Dehydrogenase Deficiency

“…10 Finally, tafenoquine is an effective alternative to primaquine and is convenient because of its long halflife, but it is also contraindicated by G6PD deficiency. 11 Easily available rapid screening for G6PD deficiency could make the use of this alternative possible in a wider variety of clinical settings.…”

Primaquine revisited six decades after its discovery

“…The promising performance of tafenoquine gave rise to a number of additional studies, some of them devoted to explore different dosages and involve higher numbers of individuals, others to investigate the effects of combining tafenoquine with other antimalarials [219][220][221]. Those studies support that tafenoquine has the potential to be used in a variety of situations beyond that of chemoprophylaxis [222].…”

Resistance to Therapies for Infection by Plasmodium vivax

“…Tafenoquine exerts an extraordinarily broad spectrum of activity against blood and tissue stages of P. falciparum and P. vivax, killing liver-stage schizonts and hyp- (52,157,164,169). The long plasma half-life of this 8-aminoquinoline (14 days) contrasts with the very rapid elimination of primaquine (half-life of 4 h) and provides incidental prophylactic protection lasting for several months (201). Its utility as a potential tool for malaria elimination should be conspicuous: in concept, a single course of therapy could eliminate disease, relapse, and further transmission.…”