Attractive targeted sugar bait: the pyrrole insecticide chlorfenapyr and the antimalarial pharmaceutical artemether-lumefantrine arrest Plasmodium falciparum development inside wild pyrethroid-resistant Anopheles gambiae s.s. mosquitoes

Background: Attractive targeted sugar bait (ATSB) is a novel approach to vector control, offering an alternative mode of insecticide delivery via the alimentary canal, with potential to deliver a variety of compounds new to medical entomology and malaria control. Its potential to control mosquitoes was recently demonstrated in major field trials in Africa. The pyrrole chlorfenapyr is an insecticide new to malaria vector control, and through its unique mode of action – disruption of ATP mediated energy transfer in mitochondria – it may have direct action on energy transfer in the flight muscle cells of mosquitoes. It may also disrupt mitochondria of malarial parasites co-existing within the infected mosquito. However, little is known about the impact of such compounds on vector competence in mosquitoes responsible for malaria transmission. Method: In this study, we compared the effect of ATSBs containing chlorfenapyr insecticide and, as a positive control, the antimalarial drugs artemether/lumefantrine (A/L) on Plasmodium falciparum development in wild pyrethroid-resistant Anopheles gambiae s.s . for their capacity to reduce vector competence. To do this, we exposed females mosquitoes to ATSB containing sublethal dose of chlorfenapyr (CFP: 0.025%) or concentrations of A/L ranging from 0.4/2.4 mg/ml to 2.4/14.4 mg/ml, either shortly before or after infective blood meals. The impact of their component compounds on the prevalence and intensity of P. falciparum infection were compared between treatments. Results: We showed that both prevalence and intensity of infection were significantly reduced in mosquitoes exposed to either A/L or CFP, compared to unexposed negative control mosquitoes. The A/L dose (2.4/14.4 mg per ml) totally erased P. falciparum parasites: 0% prevalence of infection in female mosquitoes exposed compared to 62% of infection in negative controls (df = 1, χ2 = 31.23 p < 0.001). The dose of CFP (0.25%) that killed < 20% females in ATSB showed a reduction in oocyte density of 95% per midgut (0.18/3.43 per midgut). Conclusion: These results are evidence that CFP, in addition to its direct killing effect on the vector, has the capacity to block Plasmodium transmission by interfering with oocyte development inside pyrethroid-resistant mosquitoes, and through this dual action may potentiate its impact under field conditions.