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Comparison of Artesunate-mefloquine and Artemether-Lumefantrine Fixed-dose Combinations for Treatment of Uncomplicated Plasmodium Falciparum Malaria in Children younger than 5 years in sub-Saharan Africa: a randomised, multicentre, phase 4 trial.

Sirima, S. B., Ogutu, B., Lusingu, J. P. A., Mtoro, A., Mrango, Z., Ouedraogo, A., Yaro, J. B., Onyango, K. O., Gesase, S., Mnkande, E., Ngocho, J. S., Ackermann, I., Aubin, F., Vanraes, J., Strub, N. and Carn, G. (2016) Comparison of Artesunate-mefloquine and Artemether-Lumefantrine Fixed-dose Combinations for Treatment of Uncomplicated Plasmodium Falciparum Malaria in Children younger than 5 years in sub-Saharan Africa: a randomised, multicentre, phase 4 trial. The Lancet. Infectious diseases. ISSN 1474-4457

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Abstract

WHO recommends combinations of an artemisinin derivative plus an antimalarial drug of longer half-life as treatment options for uncomplicated Plasmodium falciparum infection. In Africa, artemether-lumefantrine is the most widely used artemisinin-based combination therapy, whereas artesunate-mefloquine is used infrequently because of a perceived poor tolerance to mefloquine. WHO recommends reconsideration of the use of artesunate-mefloquine in Africa. We compared the efficacy and safety of fixed-dose artesunate-mefloquine with that of artemether-lumefantrine for treatment of children younger than 5 years with uncomplicated P falciparum malaria. We did this multicentre, phase 4, open-label, non-inferiority trial in Burkina Faso, Kenya, and Tanzania. Children aged 6-59 months with uncomplicated malaria were randomly assigned (1:1), via a computer-generated randomisation list, to receive 3 days' treatment with either one or two artesunate-mefloquine tablets (25 mg artesunate and 55 mg mefloquine) once a day or one or two artemether-lumefantrine tablets (20 mg artemether and 120 mg lumefantrine) twice a day. Parasitological assessments were done independently by two microscopists who were blinded to treatment allocation. The primary outcome was the PCR-corrected rate of adequate clinical and parasitological response (ACPR) at day 63 in the per-protocol population. Non-inferiority was shown if the lower limit of the 95% CI for the difference between groups was greater than -5%. Early vomiting was monitored and neuropsychiatric status assessed regularly during follow-up. This study is registered with ISRCTN, number ISRCTN17472707, and the Pan African Clinical Trials Registry, number PACTR201202000278282. 945 children were enrolled and randomised, 473 to artesunate-mefloquine and 472 to artemether-lumefantrine. The per-protocol population consisted of 407 children in each group. The PCR-corrected ACPR rate at day 63 was 90•9% (370 patients) in the artesunate-mefloquine group and 89•7% (365 patients) in the artemether-lumefantrine group (treatment difference 1•23%, 95% CI -2•84% to 5•29%). At 72 h after the start of treatment, no child had detectable parasitaemia and less than 6% had fever, with a similar number in each group (21 in the artesunate-mefloquine group vs 24 in the artemether-lumefantrine group). The safety profiles of artesunate-mefloquine and artemether-lumefantrine were similar, with low rates of early vomiting (71 [15•3%] of 463 patients in the artesunate-mefloquine group vs 79 [16•8%] of 471 patients in the artemether-lumefantrine group in any of the three dosing days), few neurological adverse events (ten [2•1%] of 468 vs five [1•1%] of 465), and no detectable psychiatric adverse events. Artesunate-mefloquine is effective and safe, and an important treatment option, for children younger than 5 years with uncomplicated P falciparum malaria in Africa. Agence Française de Développement, France; Department for International Development, UK; Dutch Ministry of Foreign Affairs, Netherlands; European and Developing Countries Clinical Trials Partnership; Fondation Arpe, Switzerland; Médecins Sans Frontières; Swiss Agency for Development and Cooperation, Switzerland.

Item Type: Article
Keywords: Artesunate–mefloquine, Artemether–lumefantrine, Plasmodium falciparum, Malaria, Children, sub-Saharan Africa
Subjects: Malaria > Diagnosis & treatment
Divisions: Ifakara Health Institute > Biomedical
Depositing User: Mr Joseph Madata
Date Deposited: 17 Aug 2016 12:38
Last Modified: 17 Aug 2016 12:38
URI: http://ihi.eprints.org/id/eprint/3892

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