The efficacy of intravenous quinine, which is the mainstay for treating severe malaria in children, is decreasing in South East Asia and Africa. Artemisinin derivatives are a potential alternative to quinine. However, their efficacy compared to quinine in treating severe malaria in children is not clearly understood. The objective of this review was to assess the efficacy of parenteral artemisinin derivatives versus parenteral quinine in treating severe malaria in children. All randomized controlled studies comparing parenteral artemisinin derivatives with parenteral quinine in treating severe malaria in children were included in the review. Data bases searched were: The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2007), MEDLINE (1966 to February 2008), EMBASE (1980 to February 2008), and LILACS (1982 to February 2008). Dichotomous variables were compared using risk ratios (RR) and the continuous data using weighted mean difference (WMD). Twelve trials were included (1,524 subjects). There was no difference in mortality between artemisinin derivatives and quinine (RR = 0.90, 95% CI 0.73 to 1.12). The artemisinin derivatives resolved coma faster than quinine (WMD = -4.61, 95% CI: -7.21 to -2.00, fixed effect model), but when trials with adequate concealment only were considered this differences disappeared. There was no statistically significant difference between the two groups in parasite clearance time, fever clearance time, incidence of neurological sequelae and 28th day cure rate. One trial reported significantly more local reactions at the injection site with intramuscular quinine compared to artemether. None of the trials was adequately powered to demonstrate equivalence. There was no evidence that treatment of children with severe malaria with parenteral artemisinin derivatives was associated with lower mortality or long-term morbidity compared to parenteral quinine. Future studies require adequately powered equivalence trial design to decide whether both drugs are equally effective.

Combination treatments, preferably containing an artemisinin derivative, are recommended to improve efficacy and prevent Plasmodium falciparum drug resistance. The author’s aim was to show non-inferiority of a new dispersible formulation of artemether-lumefantrine to the conventional crushed tablet in the treatment of young children with uncomplicated malaria. The authors did a randomised non-inferiority study on children weighing 5-35 kg with uncomplicated P. falciparum malaria in Benin, Kenya, Mali, Mozambique, and Tanzania. The primary outcome measure was PCR-corrected 28-day parasitological cure rate. The authors aimed to show non-inferiority (with a margin of -5%) of dispersible versus crushed tablet. They constructed an asymptotic one-sided 97.5% CI on the difference in cure rates. A computer-generated randomisation list was kept centrally and investigators were unaware of the study medication administered. They used a modified intention-to-treat analysis. 899 children aged 12 years or younger were randomly assigned to either dispersible (n=447) or crushed tablets (n=452). More than 85% of patients in each treatment group completed the study. 812 children qualified for the modified intention-to-treat analysis (n=403 vs n=409). The PCR-corrected day-28 cure rate was 97.8% (95% CI 96.3-99.2) in the group on dispersible formulation and 98.5% (97.4-99.7) in the group on crushed formulation. The lower bound of the one-sided 97.5% CI was -2.7%. The most common drug-related adverse event was vomiting (n=33 [7%] and n=42 [9%], respectively). No signs of ototoxicity or relevant cardiotoxicity were seen. A six-dose regimen of artemether-lumefantrine with the new dispersible formulation is as efficacious as the currently used crushed tablet in infants and children, and has a similar safety profile.