Tafenoquine Appears Safe and Effective for Prevention of Malaria

Chemoprophylaxis with tafenoquine, a primaquine analog, appears to be safe and effective for preventing malaria in healthy non-immune individuals challenged with blood stage Plasmodium falciparum, according to study results published in Clinical Infectious Diseases.

Tafenoquine has demonstrated activity against sporozoites, active liver schizonts, hypnozoites, erythrocytic asexual stages, and gametocytes of Plasmodium species, and although its activity against liver and blood stages has been assessed in animal models, it has not been evaluated in humans. In this study, researchers hypothesized that the chemoprophylactic effect of tafenoquine might at least partly depend on its activity against blood stage infection.

In a phase 1b study, investigators induced blood stage malaria in 16 healthy, malaria-naive adults who did not have glucose-6-phosphate-dehydrogenase deficiency to evaluate the specific blood schizonticidal activity of tafenoquine. The cohort was comprised of 16 men and women aged 20 to 42 years, and participants were randomly assigned to receive either tafenoquine or placebo. Tafenoquine was administered as a single 200-mg dose on days 1, 2, 3, and 10, followed by intravenous inoculation with approximately 2800 P falciparum parasitized erythrocytes on day 13. The primary end point was the number of individuals who required rescue treatment with artemether/lumefantrine because of the development of parasitemia.

Findings showed that parasitemia did not occur in any of the participants who received tafenoquine, whereas parasitemia developed in all members of the placebo cohort (P =.0005). The difference between the 2 groups was found to be statistically significant (P =.0005; Fisher exact test). The frequency of adverse events was similar for both groups, except that early symptoms of malaria infection were more common in the placebo group.

Aside from a few caveats, the researchers noted that the “results of this study are in alignment with observations from natural P falciparum infection during field trials,” and added that “collection of observational data post approval, especially if break through malaria cases occur, will further develop the evidence base.”

Reference

 

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 [published online November 1, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy939