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.
Published: February 2002 |