The Relative Effects of Artemether-lumefantrine and Non-artemisinin Antimalarials on Gametocyte Carriage and Transmission of Plasmodium falciparum: A Systematic Review and Meta-analysis

Background. Artemisinin-based combination therapies (ACTs) have been widely adopted as first-line agents to treat uncomplicated falciparum malaria due to their activity against multidrug resistant parasites. ACTs may also disrupt transmission through a direct antigametocyte effect, but the extent of this effect is uncertain. We assessed the evidence for and estimated the effects of the most widely-deployed ACT, artemether-lumefantrine (AL), relative to non-ACTs on gametocyte clearance and transmission interruption. Methods. We searched electronic databases for randomized controlled trials comparing AL to non-ACTs that reported gametocyte counts or results of mosquito-feeding assays. Two authors working independently assessed eligibility, extracted data, and evaluated the risk of bias. We conducted meta-analyses using a random-effects model. Results. We identified 22 eligible trials. The pooled odds of gametocytemia at 1 week were lower in AL-compared to non-ACT-treated participants (odds ratio [OR] 0.09; 95% confidence interval [CI], 0.06-0.15; I² = 0.60, P <.01; 15 trials). The odds of transmission to mosquitoes were also lower in AL treatment groups (OR 0.06; 95% CI, 0.00-0.47, P <.01 at 7 days post-treatment; 1 trial; OR 0.56; 95% CI, 0.36-0.88, P =.01 at 14 days post-treatment; 1 trial). Conclusion. AL is superior to non-ACTs in reducing gametocytemia, and, based on limited evidence, abating transmission to mosquitoes. The transmission-limiting benefit of AL has relevance for policymakers planning optimal utilization of control strategies, including use of ACTs for malaria treatment and chemoprevention.