Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial. - Archive ouverte HAL Access content directly
Journal Articles Malaria Journal Year : 2013

Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial.

(1) , (1) , (1) , (1) , (1) , (1) , (2) , (2) , (1) , (3) , (3) , (4) , (5) , (6) , (7) , (7) , (1, 8) , (1, 8)
1
2
3
4
5
6
7
8
Yah Zolia
  • Function : Author
  • PersonId : 944738
Joel Jones
  • Function : Author
  • PersonId : 944739
Eric Comte
  • Function : Author
  • PersonId : 184390
  • IdHAL : eric-comte
Pascal Houzé
  • Function : Author
  • PersonId : 931209
Gwenaelle Carn
  • Function : Author
  • PersonId : 944743
Jean-René Kiechel
  • Function : Author
  • PersonId : 944744

Abstract

BACKGROUND: Prospective efficacy monitoring of anti-malarial treatments is imperative for timely detection of resistance development. The in vivo efficacy of artesunate-amodiaquine (ASAQ) fixed-dose combination (FDC) was compared to that of artemether-lumefantrine (AL) among children aged six to 59 months in Nimba County, Liberia, where Plasmodium falciparum malaria is endemic and efficacy data are scarce. METHODS: An open-label, randomized controlled non-inferiority trial compared the genotyping adjusted day 42 cure rates of ASAQ FDC (ASAQ Winthrop®) to AL (Coartem®) in 300 children aged six to 59 months with uncomplicated falciparum malaria. Inclusion was between December 2008 and May 2009. Randomization (1:1) was to a three-day observed oral regimen (ASAQ: once a day; AL: twice a day, given with fatty food). Day 7 desethylamodiaquine and lumefantrine blood-concentrations were also measured. RESULTS: The day 42 genotyping-adjusted cure rate estimates were 97.3% [95% CI: 91.6-99.1] for ASAQ and 94.2% [88.1-97.2] for AL (Kaplan-Meier survival estimates). The difference in day 42 cure rates was -3.1% [upper limit 95% CI: 1.2%]. These results were confirmed by observed proportion of patients cured at day 42 on the per-protocol population. Parasite clearance was 100% (ASAQ) and 99.3% (AL) on day 3. The probability to remain free of re-infection was 0.55 [95% CI: 0.46-0.63] (ASAQ) and 0.66 [0.57-0.73] (AL) (p = 0.017). CONCLUSIONS: Both ASAQ and AL were highly efficacious and ASAQ was non-inferior to AL. The proportion of patients with re-infection was high in both arms in this highly endemic setting. In 2010, ASAQ FDC was adopted as the first-line national treatment in Liberia. Continuous efficacy monitoring is recommended. TRIAL REGISTRATION: The protocols were registered with Current Controlled Trials, under the identifier numbers ISRCTN51688713, ISRCTN40020296.
Fichier principal
Vignette du fichier
1475-2875-12-251.pdf (270.56 Ko) Télécharger le fichier
Vignette du fichier
1475-2875-12-251.xml (116.48 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Format : Other
Loading...

Dates and versions

inserm-00903747 , version 1 (13-11-2013)

Identifiers

Cite

Birgit Schramm, Parastou Valeh, Elisabeth Baudin, Charles Mazinda, Richard Smith, et al.. Efficacy of artesunate-amodiaquine and artemether-lumefantrine fixed-dose combinations for the treatment of uncomplicated Plasmodium falciparum malaria among children aged six to 59 months in Nimba County, Liberia: an open-label randomized non-inferiority trial.. Malaria Journal, 2013, 12 (1), pp.251. ⟨10.1186/1475-2875-12-251⟩. ⟨inserm-00903747⟩
265 View
420 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More