• Efficacy of artesunate-amodiaquine for treating uncomplicated falciparum malaria in sub-Saharan Africa: a multi-centre analysis.

      Zwang, Julien; Olliaro, Piero; Barennes, Hubert; Bonnet, Maryline; Brasseur, Philippe; Bukirwa, Hasifa; Cohuet, Sandra; D'Alessandro, Umberto; Djimdé, Abdulaye; Karema, Corine; et al. (2009-11)
      BACKGROUND: Artesunate and amodiaquine (AS&AQ) is at present the world's second most widely used artemisinin-based combination therapy (ACT). It was necessary to evaluate the efficacy of ACT, recently adopted by the World Health Organization (WHO) and deployed over 80 countries, in order to make an evidence-based drug policy. METHODS: An individual patient data (IPD) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints. RESULTS: A total of 11,700 patients (75% under 5 years old), from 33 different sites in 16 countries were followed for 28 days. Loss to follow-up was 4.9% (575/11,700). AS&AQ was given to 5,897 patients. Of these, 82% (4,826/5,897) were included in randomized comparative trials with polymerase chain reaction (PCR) genotyping results and compared to 5,413 patients (half receiving an ACT). AS&AQ and other ACT comparators resulted in rapid clearance of fever and parasitaemia, superior to non-ACT. Using survival analysis on a modified intent-to-treat population, the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90% (the WHO cut-off) in 11/16 countries. In randomized comparative trials (n = 22), the crude efficacy of AS&AQ was 75.9% (95% CI 74.6-77.1) and the PCR-adjusted efficacy was 93.9% (95% CI 93.2-94.5). The risk (weighted by site) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT, superior to dihydroartemisinin-piperaquine (DP, in one Ugandan site), and not different from AS+SP or AL (artemether-lumefantrine). The risk of gametocyte appearance and the carriage rate of AS&AQ was only greater in one Ugandan site compared to AL and DP, and lower compared to non-ACT (p = 0.001, for all comparisons). Anaemia recovery was not different than comparator groups, except in one site in Rwanda where the patients in the DP group had a slower recovery. CONCLUSION: AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many, but not all, the sub-Saharan African countries where it was studied. Efficacy varies between and within countries. An IPD analysis can inform general and local treatment policies. Ongoing monitoring evaluation is required.
    • [In Vivo Drug Sensitivity of Plasmodium Falciparum in the Tabou Region of Ivory Coast]

      Villadary, I; Paquet, C; Hemelsdael, E; Blanchard, G; Saki, Z M; Epicentre, Paris. (1997)
      Malaria caused by Plasmodium falciparum is one of the major health problems in West-Africa, mainly affecting young children. This situation is further complicated by the emergence and rapid progression of resistance to chloroquine, the recommended first line treatment. In order to document the level of resistance of P. falciparum to chloroquine, pyrimethamine/sulfadoxine (Fansidar) and quinine, we performed a survey in Tabou district, Côre d'Ivoire, from June to August 1995. This area has been hosting some 100,000 Liberian refugees since September 1994. Children aged 1 to 15 years old attending the dispensary with a complain of fever or suspected malaria, were included into the study, diagnosed and followed for 7 days according to the WHO Standard Field (in vivo) Tests. Overall proportion of P. falciparum resistant to chloroquine reached 45.1% and was made of 34.3% type II and 10.8% type III resistance. Being less than 5 years of age and having received a lower dose of drug were 2 factors associated with the risk of resistance to chloroquine. Levels of R II resistance to pyrimethamine/sulfadoxine and quinine (3-day treatment) were respectively 5.4% and 4.2%. No R III resistance was found in neither pyrimethaminelsulfadoxine or quinine treatment groups. These results challenge the current chloroquine-based first line malaria treatment in Côre d'Ivoire. Alternative based on pyrimethamine/sulfadoxine could be considered, especially in high risk populations during transient situation (refugees). However, elaborating new treatment policy must take into consideration cost, side-effects, compliance and acceptability. Further studies are needed to evaluate the cost-benefit of alternative strategies.
    • Mosquitoborne infections after Hurricane Jeanne, Haiti, 2004

      Beatty, Mark E; Hunsperger, Elizabeth; Long, Earl; Schürch, Julia; Jain, Seema; Colindres, Rom; Lerebours, Gerald; Bernard, Yves-Marie; Dobbins, James Goodman; Brown, Mathew; et al. (2007-02-01)
      After Hurricane Jeanne in September 2004, surveillance for mosquitoborne diseases in Gonaïves, Haiti, identified 3 patients with malaria, 2 with acute dengue infections, and 2 with acute West Nile virus infections among 116 febrile patients. These are the first reported human West Nile virus infections on the island of Hispaniola.