Malaria chemoprophylaxis with tafenoquine: a randomised study

Background Tafenoquine is an analogue of primaquine with an improved therap eutic and safety profile. It has a long half-life and activity against live r-stage malaria parasites, so may be useful for chemoprophylaxis. In this r andomised, double-blind study we assessed the efficacy and safety of tafeno quine in different doses. Methods 2144 individuals aged 12-20 years living in Lambarene, Gabon, an en demic area for Plasmodium falciparum malaria, were invited to take part. 53 5 attended, and 426 eligible participants were randomly assigned tafenoquin e (250 mg, 125 mg, 62.5 mg, or 31.25 mg) or placebo daily for 3 days. 417 r eceived initial curative treatment with halofantrine, and 410 completed the assigned prophylaxis regimen. During follow-up of 70 days, adverse events were recorded and thick blood smears were examined weekly. The primary and secondary endpoints were the number of individuals with positive blood smea rs by day 56 and day 77, respectively. Analyses were per-protocol. Findings Eight positive blood smears were recorded by day 56 (four/82 parti cipants in the placebo group; four/79 tafenoquine 31.25 mg group). By day 7 7, 34 positive blood smears had been recorded (14/82 placebo; 16/79 tafenoq uine 31.25 mg; three/86 tafenoquine 62.5 mg; one/79 tafenoquine 125 mg; non e/84 tafenoquine 250 mg). Numbers of adverse events did not differ signific antly between the treatment groups. Interpretation Tafenoquine is effective and well tolerated. It has the pote ntial to replace currently used drugs for malaria chemoprophylaxis.