Approximately one million children die from malaria each year. A recently approved artemisinin-based tablet, Coartem (co-artemether), comprising artemether 120 mg plus lumefantrine 20 mg, given in four doses, provides effective antimalarial treatment for children in many sub-Saharan countries. However, this regimen is considered insufficient for non-immune infants and in areas where multidrug-resistant Plasmodium falciparum predominates. This open-label study assessed the efficacy and safety of co-artemether administered to 310 African children weighing 5-25 kg, with acute, uncomplicated falciparum malaria. Six doses of co-artemether were given over 3 days, with follow-up at 7, 14 and 28 days. Treatment rapidly cleared parasitemia and fever. The overall 28-day cure rate was 86.5%, and 93.9% when corrected by PCR for reinfection. Cure rates at 7 and 14 days exceeded 97.0% (uncorrected) and, on day 28, were similar in infants (5-<10 kg) previously exposed to malaria infection (partially immune: 88.6% uncorrected; 93.3% corrected), and in those who were non-immune (82.5% uncorrected; 95.0% corrected). Adverse events were mostly mild. There was no electrocardiographic evidence of cardiotoxicity. The co-artemether six-dose regimen, treating acute uncomplicated falciparum malaria in African children, achieved rapid parasite clearance and a high cure rate. Treatment was generally safe and well tolerated.

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Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5-25 kg. A total of 544 patients with uncomplicated P. falciparum malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis. Analysis of day 28 cure rate based on the intention-to-treat and evaluable populations yielded corrected cure rates for the six-dose regimen of 93% and 96% compared with 61% and 76%, respectively, for the four-dose regimen (P < 0.0001 for both comparisons). Similarly high cure rates were achieved with the six-dose regimen in non-immune infants weighing as little as 5 kg. The six- and four-dose regimens were equally well tolerated. The main finding of this analysis is that the six-dose regimen of coartemether is safe and more efficacious than the four-dose regimen in children.

Randomized trials have confirmed the efficacy and safety of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria. Data from seven studies supported by Novartis (1996–2007), including 647 adults (> 16 years of age, 83.3% completed the study) and 1,332 children (≤ 16 years of age, 89.3% completed the study) with microscopically confirmed uncomplicated P. falciparum malaria and treated with the recommended regimen of AL, were pooled. The 28-day polymerase chain reaction–corrected parasitologic cure rate (primary efficacy endpoint) was 97.1% (495 of 510) in adults and 97.3% (792 of 814) in children (evaluable population). Gametocytemia prevalence after day was 4.2% (23 of 554) in adults and 0.9% (8 of 846) in children. No noteworthy safety signals were observed. Serious adverse events occurred in 1.4% of the adults and 1.3% of the children. This study is the largest data set to date assessing AL therapy for treatment of acute uncomplicated P. falciparum malaria. Artemether-lumefantrine showed high cure rates and rapid resolution of parasitemia, fever, and gametocytemia in adults and children, and showed an excellent safety and tolerability profile.

class of anti-malarial agents to which resistance outside the Thai-Cambodia border region has not been reported in vivo [1], the guidelines specifically recommend the use of artemisinin-based combination therapy (ACT) [1]. WHO criterion for adequate efficacy of ACT in malaria is the achievement of an average cure rate of ≥95% in clinical trials [1]. Malaria Journal ResearchThe clinical efficacy of artemether/lumefantrine (Coartem ® ) AbstractCurrent World Health Organization (WHO) guidelines for the treatment of uncomplicated falciparum malaria recommend the use of artemisinin-based combination therapy (ACT). Artemether/ lumefantrine is an ACT prequalified by the WHO for efficacy, safety and quality, approved by Swissmedic in December 2008 and recently approved by the USA FDA. Coartem ® is a fixed-dose combination of artemether and lumefantrine. Its two components have different modes of action that provide synergistic anti-malarial activity. It is indicated for the treatment of infants, children and adults with acute, uncomplicated infection due to Plasmodium falciparum or mixed infections including P. falciparum. A formulation with improved palatability has been developed especially for children (Coartem ® Dispersible), which rapidly disperses in a small amount of water for ease of administration. The efficacy of the six-dose regimen of artemether/lumefantrine has been confirmed in many different patient populations around the world, consistently achieving 28-day PCR (polymerase chain reaction)-corrected cure rates of >95% in the evaluable population, rapidly clearing parasitaemia and fever, and demonstrating a significant gametocidal effect, even in areas of widespread parasite resistance to other antimalarials. Open AccessArtemisinin derivatives have the most potent and rapid onset of anti-parasitic activity of any anti-malarial drug available today and are active against all Plasmodium species that infect humans. Importantly, they allow more parasite clearance than any other anti-malarial drug (parasite numbers can be reduced by a factor of 10 5 per asexual cycle, compared with 10 2 -10 3 with other antimalarial drugs) [2]. When combined with efficacious anti-malarials with slower elimination rates, such as lumefantrine, shorter courses of treatment (three days) become effective [2].The combination of artemether (an artemisinin derivative) and lumefantrine in a 1:6 ratio was the first fixeddose ACT to meet the WHO's prequalification criteria for efficacy, safety and quality [3]. Artemether/lumefantrine (AL), as Coartem ® , now comprises nearly 75% of the 100 million or so ACT treatments used each year [4]. Coartem ® was approved by Swissmedic in 1999 and was recently approved by the USA FDA [5]. Coartem ® Dispersible was approved by Swissmedic in December 2008. More than 40 malaria-endemic countries in subSaharan Africa have rapidly scaled up malaria prevention and treatment and now recommend the use of ACT as first-line treatment for uncomplicated falciparum malaria [6]. Both artemether and lumefantrine a...