TY - JOUR
T1 - Single-dose tafenoquine to prevent relapse of plasmodium vivax malaria
AU - Lacerda, Marcus V.G.
AU - Llanos-Cuentas, Alejandro
AU - Krudsood, Srivicha
AU - Lon, Chanthap
AU - Saunders, David L.
AU - Mohammed, Rezika
AU - Yilma, Daniel
AU - Pereira, Dhelio Batista
AU - Espino, Fe E.J.
AU - Mia, Reginaldo Z.
AU - Chuquiyauri, Raul
AU - Val, Fernando
AU - Casapía, Martín
AU - Monteiro, Wuelton M.
AU - Brito, Marcelo A.M.
AU - Costa, Mônica R.F.
AU - Buathong, Nillawan
AU - Noedl, Harald
AU - Diro, Ermias
AU - Getie, Sisay
AU - Wubie, Kalehiwot M.
AU - Abdissa, Alemseged
AU - Zeynudin, Ahmed
AU - Abebe, Cherinet
AU - Tada, Mauro S.
AU - Brand, Françoise
AU - Beck, Hans Peter
AU - Angus, Brian
AU - Duparc, Stephan
AU - Kleim, Jörg Peter
AU - Kellam, Lynda M.
AU - Rousell, Victoria M.
AU - Jones, Siôn W.
AU - Hardaker, Elizabeth
AU - Mohamed, Khadeeja
AU - Clover, Donna D.
AU - Fletcher, Kim
AU - Breton, John J.
AU - Ugwuegbulam, Cletus O.
AU - Green, Justin A.
AU - Koh, Gavin C.K.W.
N1 - Publisher Copyright:
Copyright © 2019 Massachusetts Medical Society.
PY - 2019/1/17
Y1 - 2019/1/17
N2 - BACKGROUND Treatment 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. METHODS This 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. RESULTS In 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 (P0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P0.001). Tafenoquine was associated with asymptomatic declines in hemoglobin levels, which resolved without intervention. CONCLUSIONS Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity.
AB - BACKGROUND Treatment 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. METHODS This 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. RESULTS In 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 (P0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P0.001). Tafenoquine was associated with asymptomatic declines in hemoglobin levels, which resolved without intervention. CONCLUSIONS Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity.
UR - http://www.scopus.com/inward/record.url?scp=85060126699&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1710775
DO - 10.1056/NEJMoa1710775
M3 - Article
C2 - 30650322
AN - SCOPUS:85060126699
SN - 0028-4793
VL - 380
SP - 215
EP - 228
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 3
ER -