Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison.

Hdl Handle:
http://hdl.handle.net/10144/17250
Title:
Efficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison.
Authors:
Smithuis, F; Kyaw, M K; Phe, O; Aye, K Z; Htet, L; Barends, M; Lindegardh, N; Singtoroj, T; Ashley, E A; Lwin, S; Stepniewska, K; White, N J
Journal:
Lancet
Abstract:
BACKGROUND: Artemisinin-based combinations are judged the best treatments for multidrug-resistant Plasmodium falciparum malaria. Artesunate-mefloquine is widely recommended in southeast Asia, but its high cost and tolerability profile remain obstacles to widespread deployment. To assess whether dihydroartemisinin-piperaquine is a suitable alternative to artesunate-mefloquine, we compared the safety, tolerability, efficacy, and effectiveness of the two regimens for the treatment of uncomplicated falciparum in western Myanmar (Burma). METHODS: We did an open randomised comparison of 3-day regimens of artesunate-mefloquine (12/25 mg/kg) versus dihydroartemisinin-piperaquine (6.3/50 mg/kg) for the treatment of children aged 1 year or older and in adults with uncomplicated falciparum malaria in Rakhine State, western Myanmar. Within each group, patients were randomly assigned supervised or non-supervised treatment. The primary endpoint was the PCR-confirmed parasitological failure rate by day 42. Failure rates at day 42 were estimated by Kaplan-Meier survival analysis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN27914471. FINDINGS: Of 652 patients enrolled, 327 were assigned dihydroartemisinin-piperaquine (156 supervised and 171 not supervised), and 325 artesunate-mefloquine (162 and 163, respectively). 16 patients were lost to follow-up, and one patient died 22 days after receiving dihydroartemisinin-piperaquine. Recrudescent parasitaemias were confirmed in only two patients; the day 42 failure rate was 0.6% (95% CI 0.2-2.5) for dihydroartemisinin-piperaquine and 0 (0-1.2) for artesunate-mefloquine. Whole-blood piperaquine concentrations at day 7 were similar for patients with observed and non-observed dihydroartemisinin-piperaquine treatment. Gametocytaemia developed more frequently in patients who had received dihydroartemisinin-piperaquine than in those on artesunate-mefloquine: day 7, 18 (10%) of 188 versus five (2%) of 218; relative risk 4.2 (1.6-11.0) p=0.011. INTERPRETATION: Dihydroartemisinin-piperaquine is a highly efficacious and inexpensive treatment of multidrug-resistant falciparum malaria and is well tolerated by all age groups. The effectiveness of the unsupervised treatment, as in the usual context of use, equalled its supervised efficacy, indicating good adherence without supervision. Dihydroartemisinin-piperaquine is a good alternative to artesunate-mefloquine.
Affiliation:
Médecins Sans Frontières (Holland), Yangon, Myanmar.
Publisher:
Elsevier
Issue Date:
24-Jun-2006
URI:
http://hdl.handle.net/10144/17250
DOI:
10.1016/S0140-6736(06)68931-9
PubMed ID:
16798391
Additional Links:
http://www.thelancet.com
Language:
en
ISSN:
1474-547X
Appears in Collections:
Malaria

Full metadata record

DC FieldValue Language
dc.contributor.authorSmithuis, F-
dc.contributor.authorKyaw, M K-
dc.contributor.authorPhe, O-
dc.contributor.authorAye, K Z-
dc.contributor.authorHtet, L-
dc.contributor.authorBarends, M-
dc.contributor.authorLindegardh, N-
dc.contributor.authorSingtoroj, T-
dc.contributor.authorAshley, E A-
dc.contributor.authorLwin, S-
dc.contributor.authorStepniewska, K-
dc.contributor.authorWhite, N J-
dc.date.accessioned2008-01-31T15:55:07Z-
dc.date.available2008-01-31T15:55:07Z-
dc.date.issued2006-06-24-
dc.identifier.citationEfficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison. 2006, 367 (9528):2075-85 Lanceten
dc.identifier.issn1474-547X-
dc.identifier.pmid16798391-
dc.identifier.doi10.1016/S0140-6736(06)68931-9-
dc.identifier.urihttp://hdl.handle.net/10144/17250-
dc.description.abstractBACKGROUND: Artemisinin-based combinations are judged the best treatments for multidrug-resistant Plasmodium falciparum malaria. Artesunate-mefloquine is widely recommended in southeast Asia, but its high cost and tolerability profile remain obstacles to widespread deployment. To assess whether dihydroartemisinin-piperaquine is a suitable alternative to artesunate-mefloquine, we compared the safety, tolerability, efficacy, and effectiveness of the two regimens for the treatment of uncomplicated falciparum in western Myanmar (Burma). METHODS: We did an open randomised comparison of 3-day regimens of artesunate-mefloquine (12/25 mg/kg) versus dihydroartemisinin-piperaquine (6.3/50 mg/kg) for the treatment of children aged 1 year or older and in adults with uncomplicated falciparum malaria in Rakhine State, western Myanmar. Within each group, patients were randomly assigned supervised or non-supervised treatment. The primary endpoint was the PCR-confirmed parasitological failure rate by day 42. Failure rates at day 42 were estimated by Kaplan-Meier survival analysis. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN27914471. FINDINGS: Of 652 patients enrolled, 327 were assigned dihydroartemisinin-piperaquine (156 supervised and 171 not supervised), and 325 artesunate-mefloquine (162 and 163, respectively). 16 patients were lost to follow-up, and one patient died 22 days after receiving dihydroartemisinin-piperaquine. Recrudescent parasitaemias were confirmed in only two patients; the day 42 failure rate was 0.6% (95% CI 0.2-2.5) for dihydroartemisinin-piperaquine and 0 (0-1.2) for artesunate-mefloquine. Whole-blood piperaquine concentrations at day 7 were similar for patients with observed and non-observed dihydroartemisinin-piperaquine treatment. Gametocytaemia developed more frequently in patients who had received dihydroartemisinin-piperaquine than in those on artesunate-mefloquine: day 7, 18 (10%) of 188 versus five (2%) of 218; relative risk 4.2 (1.6-11.0) p=0.011. INTERPRETATION: Dihydroartemisinin-piperaquine is a highly efficacious and inexpensive treatment of multidrug-resistant falciparum malaria and is well tolerated by all age groups. The effectiveness of the unsupervised treatment, as in the usual context of use, equalled its supervised efficacy, indicating good adherence without supervision. Dihydroartemisinin-piperaquine is a good alternative to artesunate-mefloquine.en
dc.language.isoenen
dc.publisherElsevier-
dc.relation.urlhttp://www.thelancet.com-
dc.rightsReproduced on this site with permission of Elsevier Ltd. Please see www.thelancet.com for further relevant comment.en
dc.subject.meshAdolescenten
dc.subject.meshAnimalsen
dc.subject.meshAntimalarialsen
dc.subject.meshArtemisininsen
dc.subject.meshChilden
dc.subject.meshChild, Preschoolen
dc.subject.meshDrug Therapy, Combinationen
dc.subject.meshFemaleen
dc.subject.meshHumansen
dc.subject.meshInfanten
dc.subject.meshMalaria, Falciparumen
dc.subject.meshMaleen
dc.subject.meshMefloquineen
dc.subject.meshMyanmaren
dc.subject.meshPlasmodium falciparumen
dc.subject.meshQuinolinesen
dc.subject.meshRecurrenceen
dc.subject.meshSesquiterpenesen
dc.subject.meshTreatment Outcomeen
dc.titleEfficacy and effectiveness of dihydroartemisinin-piperaquine versus artesunate-mefloquine in falciparum malaria: an open-label randomised comparison.en
dc.contributor.departmentMédecins Sans Frontières (Holland), Yangon, Myanmar.en
dc.identifier.journalLanceten

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