Abstract
BackgroundAmong 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.MethodsAll 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.ResultsNine 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.ConclusionEvidence 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.
Highlights
Among the currently used drugs in malaria case management, artemisinin derivatives and primaquine have an impact on the transmissible stages of Plasmodium falciparum
Proven strategies for malaria control include early treatment of the illness with artemisinin-based combination therapies (ACTs) [5], intermittent preventive treatment for pregnant women (IPTP) [6], and using measures that reduce the risk of infection such as indoor residual spraying (IRS) or insecticide-treated nets (ITNs) [7]
It is assumed that artemisinin derivatives act against young gametocytes, whereas primaquine acts on mature gametocytes, which are usually present in the circulation at the time when the patient presents for treatment [9]
Summary
Conduct of systematic review and search strategy The investigator developed a protocol for this systematic review and conducted it in accordance with the PRISMA (Preferred Reporting Items for Systematic Review and MetaAnalyses) statement (Additional file 1: Checklist S1) [11]. A search was conducted to identify studies assessing malaria transmission blocking effect of drugs. Search terms included artemisinin derivatives, primaquine, malaria transmission, transmission blocking/reducing drugs and mosquito infection (Additional file 2: Table S1). Studies comprising cases of P. falciparum treated with antimalarials (artemisinin derivatives and/or primaquine) and evaluating malaria transmission to Anopheles mosquitoes were included. The random effect method was used to test for differences in binary outcomes between artemisinin derivatives/primaquine and control (standard drug). Of records excluded o 1 study does not have ACT/primaquine arm (chloroquine vs sulfadoxinepyrimethamine) o 1 study pooled data from different studies without heterogeneity test 8 studies included in qualitative analysis (8 full text)*. Random effects meta-analytic model (DerSimonian and Laird) [14] to calculate the combined OR and 95% CI, even in a meta-analysis with low level of heterogeneity, in order to accommodate the random variation within the studies and the variation between the different studies
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