Single-dose tafenoquine to prevent relapse of plasmodium vivax malaria

Diro, E.; Green, J.A.; Espino, F.E.J.; Angus, B.; Chuquiyauri, R.; Jones, S.W.; Zeynudin, A.; Mia, R.Z.; Abdissa, A.; Llanos Cuentas, Elmer Alejandro; Mohammed, R.; Val, F.; Noedl, H.; Beck, H.-P.; Casapía, M.; Pereira, D.B.; Brand, F.; Monteiro, W.M.; Getie, S.; Koh, G.C.K.W.; Rousell, V.M.; Kellam, L.M.; Lon, C.; Kleim, J.-P.; Tada, M.S.; Abebe, C.; Fletcher, K.; Lacerda, M.V.G.; Duparc, S.; Ugwuegbulam, C.O.; Yilma, D.; Costa, M.R.F.; Brito, M.A.M.; Krudsood, S.; Wubie, K.M.; Mohamed, K.; Hardaker, E.; Breton, J.J.; Buathong, N.; Saunders, D.L.; Clover, D.D.

dc.contributor.author	Lacerda, M.V.G.
dc.contributor.author	Llanos Cuentas, Elmer Alejandro
dc.contributor.author	Krudsood, S.
dc.contributor.author	Lon, C.
dc.contributor.author	Saunders, D.L.
dc.contributor.author	Mohammed, R.
dc.contributor.author	Yilma, D.
dc.contributor.author	Pereira, D.B.
dc.contributor.author	Espino, F.E.J.
dc.contributor.author	Mia, R.Z.
dc.contributor.author	Chuquiyauri, R.
dc.contributor.author	Val, F.
dc.contributor.author	Casapía, M.
dc.contributor.author	Monteiro, W.M.
dc.contributor.author	Brito, M.A.M.
dc.contributor.author	Costa, M.R.F.
dc.contributor.author	Buathong, N.
dc.contributor.author	Noedl, H.
dc.contributor.author	Diro, E.
dc.contributor.author	Getie, S.
dc.contributor.author	Wubie, K.M.
dc.contributor.author	Abdissa, A.
dc.contributor.author	Zeynudin, A.
dc.contributor.author	Abebe, C.
dc.contributor.author	Tada, M.S.
dc.contributor.author	Brand, F.
dc.contributor.author	Beck, H.-P.
dc.contributor.author	Angus, B.
dc.contributor.author	Duparc, S.
dc.contributor.author	Kleim, J.-P.
dc.contributor.author	Kellam, L.M.
dc.contributor.author	Rousell, V.M.
dc.contributor.author	Jones, S.W.
dc.contributor.author	Hardaker, E.
dc.contributor.author	Mohamed, K.
dc.contributor.author	Clover, D.D.
dc.contributor.author	Fletcher, K.
dc.contributor.author	Breton, J.J.
dc.contributor.author	Ugwuegbulam, C.O.
dc.contributor.author	Green, J.A.
dc.contributor.author	Koh, G.C.K.W.
dc.date.accessioned	2019-07-04T17:00:24Z
dc.date.available	2019-07-04T17:00:24Z
dc.date.issued	2019
dc.identifier.uri	https://hdl.handle.net/20.500.12866/6905
dc.description.abstract	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 (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. CONCLUSIONS: Single-dose tafenoquine resulted in a significantly lower risk of P. vivax recurrence than placebo in patients with phenotypically normal G6PD activity.	en_US
dc.language.iso	eng
dc.publisher	Massachusetts Medical Society
dc.relation.ispartofseries	New England Journal of Medicine
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.rights.uri	https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject	adolescent	en_US
dc.subject	Adolescent	en_US
dc.subject	adult	en_US
dc.subject	Adult	en_US
dc.subject	aminoquinoline derivative	en_US
dc.subject	Aminoquinolines	en_US
dc.subject	antimalarial agent	en_US
dc.subject	Antimalarials	en_US
dc.subject	Article	en_US
dc.subject	Brazil	en_US
dc.subject	Cambodia	en_US
dc.subject	chloroquine	en_US
dc.subject	Chloroquine	en_US
dc.subject	clinical trial	en_US
dc.subject	combination drug therapy	en_US
dc.subject	controlled study	en_US
dc.subject	Cytochrome P-450 CYP2D6	en_US
dc.subject	cytochrome P450 2D6	en_US
dc.subject	disease free survival	en_US
dc.subject	disease severity	en_US
dc.subject	Disease-Free Survival	en_US
dc.subject	dizziness	en_US
dc.subject	double blind procedure	en_US
dc.subject	Double-Blind Method	en_US
dc.subject	drug safety	en_US
dc.subject	Drug Therapy, Combination	en_US
dc.subject	enzyme activity	en_US
dc.subject	Ethiopia	en_US
dc.subject	female	en_US
dc.subject	Female	en_US
dc.subject	G6PD protein, human	en_US
dc.subject	glucose 6 phosphate dehydrogenase	en_US
dc.subject	Glucosephosphate Dehydrogenase	en_US
dc.subject	hematocrit	en_US
dc.subject	hemoglobin	en_US
dc.subject	Hemoglobins	en_US
dc.subject	human	en_US
dc.subject	Humans	en_US
dc.subject	hypopigmentation	en_US
dc.subject	intention to treat analysis	en_US
dc.subject	Intention to Treat Analysis	en_US
dc.subject	isolation and purification	en_US
dc.subject	Kaplan Meier method	en_US
dc.subject	Kaplan-Meier Estimate	en_US
dc.subject	keratopathy	en_US
dc.subject	Logistic Models	en_US
dc.subject	major clinical study	en_US
dc.subject	Malaria, Vivax	en_US
dc.subject	male	en_US
dc.subject	Male	en_US
dc.subject	metabolism	en_US
dc.subject	methemoglobin	en_US
dc.subject	multicenter study	en_US
dc.subject	parasite clearance	en_US
dc.subject	parasitemia	en_US
dc.subject	Parasitemia	en_US
dc.subject	Peru	en_US
dc.subject	phase 2 clinical trial	en_US
dc.subject	phase 3 clinical trial	en_US
dc.subject	Philippines	en_US
dc.subject	placebo	en_US
dc.subject	Plasmodium vivax	en_US
dc.subject	Plasmodium vivax malaria	en_US
dc.subject	primaquine	en_US
dc.subject	Primaquine	en_US
dc.subject	priority journal	en_US
dc.subject	procedures	en_US
dc.subject	randomized controlled trial	en_US
dc.subject	recurrence risk	en_US
dc.subject	relapse	en_US
dc.subject	retina disease	en_US
dc.subject	retinal hypopigmentation	en_US
dc.subject	secondary prevention	en_US
dc.subject	Secondary Prevention	en_US
dc.subject	single drug dose	en_US
dc.subject	statistical model	en_US
dc.subject	tafenoquine	en_US
dc.subject	Thailand	en_US
dc.subject	treatment duration	en_US
dc.title	Single-dose tafenoquine to prevent relapse of plasmodium vivax malaria	en_US
dc.type	info:eu-repo/semantics/article
dc.identifier.doi	https://doi.org/10.1056/NEJMoa1710775
dc.subject.ocde	https://purl.org/pe-repo/ocde/ford#3.02.00
dc.relation.issn	1533-4406