Artemisinin derivatives for treating severe malaria.
McIntosh HM., Olliaro P.
BACKGROUND:Artemisinin derivatives may have advantages over quinoline drugs for treating severe malaria since they are fast acting and effective against quinine resistant malaria parasites. OBJECTIVES:The objective of this review was to assess the effects of artemisinin drugs for severe and complicated falciparum malaria in adults and children. SEARCH STRATEGY:We searched the Cochrane Infectious Diseases Group trials register, Cochrane Controlled Trials Register, Medline, Embase, Science Citation Index, Lilacs, African Index Medicus, conference abstracts and reference lists of articles. We contacted organisations, researchers in the field and drug companies. SELECTION CRITERIA:Randomised and pseudo-randomised trials comparing artemisinin drugs (rectal, intramuscular or intravenous) with standard treatment, or comparisons between artemisinin derivatives in adults or children with severe or complicated falciparum malaria. DATA COLLECTION AND ANALYSIS:Eligibility, trial quality assessment and data extraction were done independently by two reviewers. Study authors were contacted for additional information. MAIN RESULTS:Twenty three trials are included, allocation concealment was adequate in nine. Sixteen trials compared artemisinin drugs with quinine in 2653 patients. Artemisinin drugs were associated with better survival (mortality odds ratio 0.61, 95% confidence interval 0.46 to 0.82, random effects model). In trials where concealment of allocation was adequate (2261 patients), this was barely statistically significant (odds ratio 0.72, 95% CI 0.54 to 0.96, random effects model). In 1939 patients with cerebral malaria, mortality was also lower with artemisinin drugs overall (odds ratio 0.63, 95% CI 0.44 to 0.88, random effects model). The difference was not significant however when only trials reporting adequate concealment of allocation were analysed (odds ratio 0.78, 95% CI 0.55 to 1.10, random effects model) based on 1607 patients. No difference in neurological sequelae was shown. Compared with quinine, artemisinin drugs showed faster parasite clearance from the blood and similar adverse effects. REVIEWER'S CONCLUSIONS:The evidence suggests that artemisinin drugs are no worse than quinine in preventing death in severe or complicated malaria. No artemisinin derivative appears to be better than the others.