By Dean L. Winslow, MD, FACP, FIDSA, FPIDS
Professor of Medicine, Division of General Medical Disciplines, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine
Dr. Winslow reports no financial relationships relevant to this field of study.
SYNOPSIS: Tafenoquine is effective for the prevention of all species of malaria and can be used to prevent relapse of Plasmodium vivax and Plasmodium ovale. G6PD status should be evaluated prior to use.
SOURCE: Haston JC, Hwang J, Tan KR. Guidance for using tafenoquine for prevention and antirelapse therapy for malaria — United States, 2019. MMWR Morb Mortal Wkly Rep 2019;68:1062-1068.
The authors performed a thorough review of the published literature (269 English language publications), examined data submitted to the U.S. Food and Drug Administration, and have released guidance for using tafenoquine for both prevention and antirelapse therapy for malaria. Randomized controlled trials of tafenoquine for prevention of malaria in the field showed comparable efficacy to mefloquine (86-100%). A randomized human challenge study demonstrated 100% efficacy of tafenoquine against the blood stage of Plasmodium falciparum in healthy volunteers.1 In patients with confirmed P. vivax malaria, a single 300 mg dose of tafenoquine prevented relapse in 62-89% of cases. Tafenoquine was well-tolerated when used as a single dose and in multiple dosing regimens used for prophylaxis. An interesting side effect seen in one study described vortex keratopathy (whorl-like deposition of pigmented material — often medications) in approximately 90% of patients, but this did not affect visual acuity and resolved in all cases within one year.2
Tafenoquine (an 8-aminoquinoline like primaquine, but with a prolonged half-life in humans) is contraindicated in patients with G6PD deficiency, pregnancy, breastfeeding (if the infant is G6PD-deficient or has unknown G6PD status), known hypersensitivity to 8-aminoquinolines, and a history of significant psychiatric disorders (mefloquine-like side effects were rarely seen in clinical trials).
The dosing recommendations for prophylaxis are to load with tafenoquine 200 mg daily for three days before departure, followed by a maintenance regimen of 200 mg weekly beginning seven days after the last loading dose, and taken for the entire duration of travel plus one additional dose after returning. For antirelapse therapy in patients being treated for P. vivax or P. ovale malaria, a single 300 mg dose should be given on the first or second day of blood stage treatment or as soon as possible after completion of blood stage therapy. For presumptive antirelapse therapy in patients who received other malaria prophylaxis regimens, a single 300 mg dose is given on the same day as the last dose of prophylaxis (or as soon as possible afterward). Of course, an antirelapse dose of tafenoquine would not be necessary if the patient received either primaquine or tafenoquine for prophylaxis.
COMMENTARY
Tafenoquine is an attractive option for malaria prophylaxis in adults 18 years of age or older and for antirelapse therapy for P. vivax or P. ovale in patients 16 years of age or older. The simplified dosing regimen and its good tolerability should improve adherence. An interesting publication last year showed in a SCID mouse model of babesiosis, a single dose of tafenoquine resulted in a > 90% reduction in parasitemia, suggesting that this new drug might be useful in this infection as well.3
REFERENCES
- McCarthy JS, Smith B, Reid M, et al. Blood schizonticidal activity and safety of tafenoquine when administered as chemoprophylaxis to healthy, non-immune participants followed by blood stage Plasmodium falciparum challenge: A randomized, double-blinded, placebo-controlled Phase 1b study. Clin Infect Dis 2018;69:480-486.
- Nasveld PE, Edstein MD, Reid M, et al; Tafenoquine Study Team. Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects. Antimicrob Agents Chemother 2010;54:792-798.
- Mordue DG, Wormser GP. Could the drug tafenoquine revolutionize the treatment of Babesia microti infection? J Infect Dis 2019;220:442-447.
Tafenoquine is effective for the prevention of all species of malaria and can be used to prevent relapse of Plasmodium vivax and Plasmodium ovale. G6PD status should be evaluated prior to use.
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