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Assessment of the efficacy of antimalarial drugs recommended by the National Malaria Control Programme in Madagascar: Up-dated baseline data from randomized and multi-site clinical trials

Didier Ménard1*, Arsène Ratsimbasoa2, Milijaona Randrianarivelojosia1, Léon-Paul Rabarijaona2, Lucie Raharimalala1, Olivier Domarle3, Laurence Randrianasolo2, Arthur Randriamanantena2, Martial Jahevitra1, Valérie Andriantsoanirina1, Marie-Ange Rason1, Rogelin Raherinjafy1, Emma Rakotomalala1, Luciano Tuseo4 and Andrianirina Raveloson5

Author Affiliations

1 Malaria Unit Research, Institut Pasteur de Madagascar, Antananarivo, Madagascar

2 Epidemiology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar

3 Immunology Unit, Institut Pasteur de Madagascar, Antananarivo, Madagascar

4 WHO Office of Madagascar and La Réunion, Antananarivo, Madagascar

5 National Malaria Control Programme, Ministry of Health, Antananarivo, Madagascar

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Malaria Journal 2008, 7:55  doi:10.1186/1475-2875-7-55

Published: 4 April 2008



In order to improve the monitoring of the antimalarial drug resistance in Madagascar, a new national network based on eight sentinel sites was set up. In 2006/2007, a multi-site randomized clinical trial was designed to assess the therapeutic efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP), amodiaquine (AQ) and artesunate plus amodiaquine combination (ASAQ), the antimalarial therapies recommended by the National Malaria Control Programme (NMCP).


Children between six months and 15 years of age, with uncomplicated falciparum malaria, were enrolled. Primary endpoints were the day-14 and day-28 risks of parasitological failure, either unadjusted or adjusted by genotyping. Risks of clinical and parasitological treatment failure after adjustment by genotyping were estimated using Kaplan-Meier survival analysis. Secondary outcomes included fever clearance, parasite clearance, change in haemoglobin levels between Day 0 and the last day of follow-up, and the incidence of adverse events.


A total of 1,347 of 1,434 patients (93.9%) completed treatment and follow-up to day 28. All treatment regimens, except for the chloroquine (CQ) treatment group, resulted in clinical cure rates above 97.6% by day-14 and 96.7% by day-28 (adjusted by genotyping). Parasite and fever clearance was more rapid with artesunate plus amodiaquine, but the extent of haematological recovery on day-28 did not differ significantly between the four groups. No severe side-effects were observed during the follow-up period.


These findings (i) constitute an up-dated baseline data on the efficacy of antimalarial drugs recommended by the NMCP, (ii) show that antimalarial drug resistance remains low in Madagascar, except for CQ, compared to the bordering countries in the Indian Ocean region such as the Comoros Archipelago and (iii) support the current policy of ASAQ as the first-line treatment in uncomplicated falciparum malaria.