Tafenoquine for Malaria Prophylaxis
Tafenoquine for Malaria Prophylaxis
Abstract & Commentary
Synopsis: Tafenoquine (WR238605) is a new long-acting 8-aminoquinolone with potential to be used as malarial chemoprophylaxis in geographic areas with chloroquine-resistant Plasmodium falciparum and Plasmodium vivax malaria.
Source: Shanks GD, et al. A new primaquine analogue, tafenoquine (WR238605), for prophylaxis against Plasmodium falciparum malaria. Clin Infect Dis. 2001;33:1968-1974.
Tafenoquine was tested in a double-blinded, placebo-controlled, randomized clinical trial during malarial transmission season in a highly endemic area in western Kenya. This comparative clinical trial had 4 arms. To clear any pre-existing cases of parasitemia, all 249 volunteers initially received a curative treatment regimen of halofantrine. Subjects were then randomized to receive 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 weekly of tafenoquine and 3 days of 400 mg of tafenoquine followed by 400 mg weekly of tafenoquine. Prophylaxis was continued for 13 weeks. Volunteers who received 400 mg for only 3 days had protective efficacy of 68% (95% CI 53-79%), those who received 200 mg for 3 days followed by weekly 200 mg dosing had a protective efficacy of 86% (95% CI, 73-93%), and those who received 400 mg for 3 days followed by a weekly 400 mg dose had a protective efficacy of 89% (95% CI, 77-95%).
Comment by Michele Barry, MD, FACP
Tafenoquine (WR238065) is a new long-acting 8-aminoquinolone with a half-life of 2 weeks. This long half-life raises the possibility that short-term travelers to highly endemic malarious areas could be protected by the use of a 3-day regimen taken before travel. G6PD-deficient persons would have to be excluded, and, in this study, 2 serious hemolytic events occurred in G6PD-deficient volunteers whose G6PD status had been incorrectly determined during screening. Otherwise, the drug was well tolerated except for minor skin rashes and low-level asymptomatic methemoglobinemia, which was anticipated with this primaquine-like compound.
Before any further conclusions can be made, studies in nonimmune travelers must be conducted, as all these volunteers were semi-immune volunteers living in a malarious area of Kenya. Moreover, the long half-life of tafenoquine implies that some parasites will be exposed to low concentrations of the drug during its elimination phase, which could encourage the selection of drug-resistant strains quickly if the drug were to be used persistently in an endemic setting. Certainly, short-term travelers who may leave endemic areas with therapeutic drug levels would be a target group to use this new compound successfully without encouraging drug resistance.
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