Blocking malaria transmission to Anopheles mosquitoes using artemisinin derivatives and primaquine: a systematic review and meta-analysis

BACKGROUND: Among the currently used drugs in malaria case management, artemisinin derivatives and primaquine have an impact on the transmissible stages of Plasmodium falciparum. Hence, they reduce the transmission of the parasite from the patient to the mosquitoes. The present study aimed to assess evidence for this hypothesis from controlled trials. METHODS: All controlled clinical trials evaluating the transmission blocking activity of artemisinin derivatives and primaquine with or without other antimalarials were included in this systematic review. PubMed, Google Scholar, Web of Science, ScienceDirect, Medscape and the Cochrane library were systematically searched without language, publication status or date restrictions. The literature references were also scanned manually. The last search was run on July 15, 2013. Search terms included artemisinin derivatives, primaquine, malaria transmission, transmission blocking/reducing drugs and mosquito infection. The outcome measure was the mosquito infectivity rate after treatment of patients. Data were compared using odds ratio (OR), in random effects models. RESULTS: Nine trials with a total of 13,831 mosquitoes were included in the meta-analysis. After combining the trials, the transmission of P. falciparum to Anopheles mosquitoes were lower in artesunate, artemether-lumefantrine and primaquine groups as compared with their control counterparts with OR of 0.36 (95% confidence interval (CI), 0.14-0.90), 0.49 (95% CI, 0.31-0.79) and 0.09 (95% CI, 0.01-0.73); respectively. In non-comparative longitudinal studies, the use of a single-dose of primaquine was shown to deter the transmission of malaria briefly. CONCLUSION: Evidence on the transmission blocking effect of artemisinin derivatives and primaquine is conclusive. Trials evaluating the combined impact of artemisinin derivatives and primaquine on malaria transmission is urgently needed.