Do paediatric drug formulations of artemisinin combination therapies improve the treatment of children with malaria? A systematic review and meta-analysis.

Paediatric formulations of artemisinin combination therapies (ACTs) have recently been developed for the treatment of children with falciparum malaria. Compared with conventional tablet formulations, the new non-tablet preparations have shown equivalent efficacy, safety, and tolerability in individual trials. We aimed to investigate whether objective evidence supports the development and use of paediatric ACTs. A systematic review identified seven studies involving 2515 children that were eligible for meta-analysis. Similar efficacy and safety were seen in pooled analyses of paediatric and conventional formulations. 23 (2.0%) of 1154 patients in the paediatric formulation groups and 19 (1.7%) of 1137 in the tablet formulation groups were not cured (RR 1.27, 95% CI 0.66-2.44). Despite similar overall tolerability, the tolerability of drug administration was improved for paediatric formulations as shown by significantly fewer patients with drug-induced vomiting (93 of 1018 and 114 of 837 patients; risk ratio [RR] 0.78, 95% CI 0.61-0.99), and drug-related gastrointestinal disorders (8 of 545 and 15 of 358 patients; RR 0.36, 95% CI 0.15-0.85). These data provide, for the first time, evidence for improved management of children by use of paediatric formulations, and support the further development and use of paediatric ACTs.