A meta-analysis using individual patient data, including 16 RCTs with a total of 5 948 randomised subjects, was abstracted in DARE. The trials compared treatment failure and transmission potential when artemisinin derivatives are combined with standard antimalarial drugs (chloroquine, amodiaquine, sulfadoxine-pyrimethamine or mefloquine) as compared to the standard drug alone in the treatment of acute, uncomplicated Plasmodium falciparum malaria. The dose of artesunate was generally 4 mg/day for up to 3 days. In the Africa-based studies, mean age range was 1.4 to 8.1 years, in studies from Thailand 15.9 to 18.6 years, and in the one study from Peru the mean age of the study population was 29 years.
The addition of 3 days of artesunate was associated with a statistically significant reduction in the day 14 failure rate compared with placebo (OR 0.20, 95% CI 0.17 to 0.25; 15 trials, n=4 504). There was, however, statistically significant heterogeneity between the studies. The effect of artesunate was better when combined with mefloquine (OR 0.04) and worse when combined with amodiaquine (OR 0.41). At 28 days, the beneficial effect of artesunate also was statistically significant, when reinfections were either excluded (OR 0.23, 95% CI 0.19 to 0.28; 10 trials, n=2 908;) or included (OR 0.30, 95% CI 0.26 to 0.35; 14 trials, n=4 332). Parasite clearance was statistically significantly faster with artesunate than with placebo (rate ratio 1.96, 95% CI 1.85 to 2.12). In participants with no gametocytes at baseline, artesunate significantly reduced the gametocyte count at 7, 14 and 28 days.
Comment: The included trials were in many ways clinically heterogenous and the pooled result for the primary outcome was subject to significant heterogeneity. The use of individual patient data rather than summary data increased the robustness of the analysis, especially as sensitivity analyses found that missing data did not alter the results.