Severe malaria kills over a million people every year. The authors sought evidence of superiority of artesunate compared with the standard treatment quinine. The objective of the study was to compare artesunate with quinine for treating severe malaria. SEARCH The authors searched the Cochrane Infectious Diseases Group Specialized Register (January 2007), CENTRAL (The Cochrane Library 2006, Issue 4), MEDLINE (1966 to January 2007), EMBASE (1974 to January 2007), LILACS (1982 to January 2007), ISI Web of Science (1945 to January 2007), the metaRegister of Controlled trials (mRCT), conference proceedings, and reference lists of articles. The researchers and the World Health Organization were contacted. Randomized controlled trials comparing intravenous, intramuscular, or rectal artesunate with intravenous or intramuscular quinine for treating adults and children with severe malaria who are unable to take medication by mouth were selected. Two authors assessed the eligibility and methodological quality of trials, extracted and analysed data, and drafted the review. The third author contributed to the design and writing of the review. Death was the primary outcome. Dichotomous outcomes were summarized using relative risks and continuous outcomes by mean differences. Where appropriate, the authors combined data in meta-analyses. Heterogeneity was investigated for the primary outcome using subgroup analyses. MAIN Six trials enrolling 1938 participants (1664 adults and 274 children) met our inclusion criteria. All six trials were conducted in Asia, and only one small trial enrolled only children. Five trials used intravenous artesunate and one trial intramuscular artesunate; all six used intravenous quinine. Treatment with artesunate significantly reduced the risk of death (RR 0.62, 95% CI 0.51 to 0.75; 1938 participants, 6 trials), reduced parasite clearance time (WMD 8.14 h, 95% CI 11.55 to 4.73; 292 participants, 3 trials), and hypoglycaemia detected by routine monitoring (RR 0.46, 95% CI 0.25 to 0.87; 185 participants, 2 trials). There was no evidence of a difference in neurological sequelae, coma recovery time, time to hospital discharge, fever clearance time, or adverse effects other than hypoglycaemia. Intravenous artesunate is the drug of choice for adults with severe malaria, particularly if acquired in Asia. This review did not identify sufficient data to make firm conclusions about the treatment of children or the effectiveness of intramuscular artesunate. There is an urgent need to compare the effects of artesunate with quinine in African children with severe malaria. The applicability of these results to Asian children and the ethics of further research are points of debate .

P. falciparum gametocytes may persist after treatment with sulphadoxine-pyrimethamine (SP) plus artesunate (AS) and contribute considerably to malaria transmission. The authors determined the efficacy of SP+AS plus a single dose of primaquine (PQ, 0.75 mg/kg) on clearing gametocytaemia measured by molecular methods. The study was conducted in Mnyuzi, an area of hyperendemic malaria in north-eastern Tanzania. Children aged 3-15 years with uncomplicated P. falciparum malaria with an asexual parasite density between 500-100,000 parasites/microL were randomized to receive treatment with either SP+AS or SP+AS+PQ. P. falciparum gametocyte prevalence and density during the 42-day follow-up period were determined by real-time nucleic acid sequence-based amplification (QT-NASBA). Haemoglobin levels (Hb) were determined to address concerns about haemolysis in G6PD-deficient individuals. 108 individuals were randomized. Pfs25 QT-NASBA gametocyte prevalence was 88-91% at enrolment and decreased afterwards for both treatment arms. Gametocyte prevalence and density were significantly lower in children treated with SP+AS+PQ. On day 14 after treatment 3.9% (2/51) of the SP+AS+PQ treated children harboured gametocytes compared to 62.7% (32/51) of those treated with SP+AS (p <0.001). Hb levels were reduced in the week following treatment with SP+AS+PQ and this reduction was related to G6PD deficiency. The Hb levels of all patients recovered to pre-treatment levels or greater within one month after treatment. PQ clears submicroscopic gametocytes after treatment with SP+AS and the persisting gametocytes circulated at densities that are unlikely to contribute to malaria transmission. For individuals without severe anaemia, addition of a single dose of PQ to an efficacious antimalarial drug combination is a safe approach to reduce malaria transmission following treatment.