• Marcus V G Lacerda, Alejandro Llanos-Cuentas, Srivicha Krudsood, Chanthap Lon, David L Saunders, Rezika Mohammed, Daniel Yilma, Dhelio Batista Pereira, Fe E J Espino, Reginaldo Z Mia, Raul Chuquiyauri, Fernando Val, Martín Casapía, Wuelton M Monteiro, Marcelo A M Brito, Mônica R F Costa, Nillawan Buathong, Harald Noedl, Ermias Diro, Sisay Getie, Kalehiwot M Wubie, Alemseged Abdissa, Ahmed Zeynudin, Cherinet Abebe, Mauro S Tada, Françoise Brand, Hans-Peter Beck, Brian Angus, Stephan Duparc, Jörg-Peter Kleim, Lynda M Kellam, Victoria M Rousell, Siôn W Jones, Elizabeth Hardaker, Khadeeja Mohamed, Donna D Clover, Kim Fletcher, John J Breton, Cletus O Ugwuegbulam, Justin A Green, and Koh Gavin C K W GCKW 0000-0002-7336-1566 From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F..
• From Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus (M.V.G.L., F.V., W.M.M., M.A.M.B., M.R.F.C.), Fundação Oswaldo Cruz, Manguinhos, Rio de Janeiro (M.V.G.L.), and Centro de Pesquisa em Medicina Tropical Rondônia, Porto Velho (D.B.P., M.S.T.) - all in Brazil; Universidad Peruana Cayetano Heredia, Lima, Peru (A.L.-C., R.C., M.C.); Mahidol University (S.K.) and the Armed Forces Research Institute of Medical Sciences (C.L., D.L.S., N.B.), Bangkok, Thailand; the University of Gondar, Gondar (R.M., E.D., S.G., K.M.W.), and Jimma University, Jimma (D.Y., A.A., A.Z., C.A.) - both in Ethiopia; Research Institute for Tropical Medicine, Manila (F.E.J.E.), and Rio Tuba Nickel Foundation Hospital, Palawan (R.Z.M.) - both in the Philippines; Medical University of Vienna, Vienna (H.N.); Swiss Tropical and Public Health Institute and University of Basel, Basel (F.B., H.-P.B.), and Medicines for Malaria Venture, Geneva (S.D.) - both in Switzerland; Oxford University, Oxford (B.A.), and GlaxoSmithKline, Stockley Park West (J.-P.K., L.M.K., V.M.R., S.W.J., E.H., K.M., D.D.C., K.F., C.O.U., J.A.G., G.C.K.W.K.) - both in the United Kingdom; and GlaxoSmithKline, Collegeville, PA (J.J.B.).
• N. Engl. J. Med. 2019 Jan 17; 380 (3): 215-228.

BackgroundTreatment of Plasmodium vivax malaria requires the clearing of asexual parasites, but relapse can be prevented only if dormant hypnozoites are cleared from the liver (a treatment termed "radical cure"). Tafenoquine is a single-dose 8-aminoquinoline that has recently been registered for the radical cure of P. vivax.MethodsThis multicenter, double-blind, double-dummy, parallel group, randomized, placebo-controlled trial was conducted in Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. We enrolled 522 patients with microscopically confirmed P. vivax infection (>100 to <100,000 parasites per microliter) and normal glucose-6-phosphate dehydrogenase (G6PD) activity (with normal activity defined as ≥70% of the median value determined at each trial site among 36 healthy male volunteers who were otherwise not involved in the trial). All patients received a 3-day course of chloroquine (total dose of 1500 mg). In addition, patients were assigned to receive a single 300-mg dose of tafenoquine on day 1 or 2 (260 patients), placebo (133 patients), or a 15-mg dose of primaquine once daily for 14 days (129 patients). The primary outcome was the Kaplan-Meier estimated percentage of patients who were free from recurrence at 6 months, defined as P. vivax clearance without recurrent parasitemia.ResultsIn the intention-to-treat population, the percentage of patients who were free from recurrence at 6 months was 62.4% in the tafenoquine group (95% confidence interval [CI], 54.9 to 69.0), 27.7% in the placebo group (95% CI, 19.6 to 36.6), and 69.6% in the primaquine group (95% CI, 60.2 to 77.1). The hazard ratio for the risk of recurrence was 0.30 (95% CI, 0.22 to 0.40) with tafenoquine as compared with placebo (P<0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P<0.001). Tafenoquine was associated with asymptomatic declines in hemoglobin levels, which resolved without intervention.ConclusionsSingle-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity. (Funded by GlaxoSmithKline and Medicines for Malaria Venture; DETECTIVE ClinicalTrials.gov number, NCT01376167 .).

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