title: Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.
abstract: This study represents the first phase III trial of the safety, tolerability, and effectiveness of tafenoquine for malaria prophylaxis. In a randomized (3:1), double-blinded study, Australian soldiers received weekly malaria prophylaxis with 200 mg tafenoquine (492 subjects) or 250 mg mefloquine (162 subjects) for 6 months on a peacekeeping deployment to East Timor. After returning to Australia, tafenoquine-receiving subjects received a placebo and mefloquine-receiving subjects received 30 mg primaquine daily for 14 days. There were no clinically significant differences between hematological and biochemical parameters of the treatment groups. Treatment-related adverse events for the two groups were similar (tafenoquine, 13.4%; mefloquine, 11.7%). Three subjects on tafenoquine (0.6%) and none on mefloquine discontinued prophylaxis because of possible drug-related adverse events. No diagnoses of malaria occurred for either group during deployment, but 4 cases (0.9%) and 1 case (0.7%) of Plasmodium vivax infection occurred among the tafenoquine and mefloquine groups, respectively, up to 20 weeks after discontinuation of medication. In a subset of subjects recruited for detailed safety assessments, treatment-related mild vortex keratopathy was detected in 93% (69 of 74) of tafenoquine subjects but none of the 21 mefloquine subjects. The vortex keratopathy was not associated with any effect on visual acuity and was fully resolved in all subjects by 1 year. Tafenoquine appears to be safe and well tolerated as malaria prophylaxis. Although the volunteers' precise exposure to malaria could not be proven in this study, tafenoquine appears to be a highly efficacious drug for malaria prophylaxis.
authors.affiliation: Australian Army Malaria Institute, Brisbane, Queensland, Australia. P.Nasveld@uq.edu.au
authors.forename: Peter E
authors.initials: PE
authors.lastname: Nasveld
authors.forename: Michael D
authors.initials: MD
authors.lastname: Edstein
authors.forename: Mark
authors.initials: M
authors.lastname: Reid
authors.forename: Leonard
authors.initials: L
authors.lastname: Brennan
authors.forename: Ivor E
authors.initials: IE
authors.lastname: Harris
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Kitchener
authors.forename: Peter A
authors.initials: PA
authors.lastname: Leggat
authors.forename: Philip
authors.initials: P
authors.lastname: Pickford
authors.forename: Caron
authors.initials: C
authors.lastname: Kerr
authors.forename: Colin
authors.initials: C
authors.lastname: Ohrt
authors.forename: William
authors.initials: W
authors.lastname: Prescott
mesh_terms: D000328:Adult; D000634:Aminoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D001315:Australia; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D008889:Military Personnel; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; C055852:tafenoquine; D015767:Mefloquine