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

Abstract

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.

Figure 1

Study selection flow diagram. *three articles were used as sources of data for both qualitative and quantitative synthesis.

Figure 2

Mosquito infectivity after feeding on blood from patients treated with antimalarials (with vs. without artesunate). *control serum; **AP = autologous plasma; ***compared with single-dose artesunate; CQ = chloroquine; SP = sulfadoxine-pyrimethamine; AQ = amodiaquine; AS = artesunate.

Figure 3

Mosquito infectivity after feeding on blood from patients treated with artemether-lumefantrine versus control (standard therapy). CQ = chloroquine; SP = sulfadoxine-pyrimethamine; AQ = amodiaquine; AL = artemether-lumefantrine.

Figure 4

Mosquito infection prevalence after blood-meal on primaquine treated malaria patients versus control (standard therapy). PQ = primaquine; SP-1 and 2 = sulfadoxine-pyrimethamine in two independent patient group; P-1 and 2 = treatment in two patients infected with different strains of P. falciparum.

Figure 5

Plasmodium infectivity rate to mosquitoes that fed on falciparum malaria patients treated with a single dose of primaquine. Day zero refers to the percent of oocyst positive mosquito fed on patients before the treatment. Sixteen of each line represents the oocyst positivity of mosquitoes feeding on single patients immediately before treatment and afterwards. Mosquitoes fed on two patients after 10 days of treatment were oocyst positive [19,20,23-25].

Figure 6

Plasmodium infective rate to mosquitoes after patients treated with mefloquine alone versus mefloquine plus primaquine. The mosquitoes fed via membrane feeding on blood of patients treated with a single dose of mefloquine (750 mg) or a combination with primaquine single dose (45 mg). MQ = mefloquine; PQ = primaquine [26].