Impact of ivermectin components on Anopheles dirus and Anopheles minimus mosquito survival

Background Ivermectin mass drug administration to humans or livestock is a potential vector control tool for malaria elimination. Racemic ivermectin is composed of two components, namely a major component (> 80%; ivermectin B 1a ), which has an ethyl group at C-26, and a minor component (< 20%; ivermectin B 1b ), which has a methyl group at C-26. There is no difference between the efficacy of ivermectin B 1a and ivermectin B 1b efficacy in nematodes, but only ivermectin B 1b has been reported to be lethal to snails. The ratios of ivermectin B 1a and B 1b ratios in ivermectin formulations and tablets can vary between manufacturers and batches. The mosquito-lethal effects of ivermectin B 1a and ivermectin B 1b have never been assessed. As novel ivermectin formulations are being developed for malaria control, it is important that the mosquito-lethal effects of individual ivermectin B 1a and ivermectin B 1b compounds be evaluated. Methods Racemic ivermectin, ivermectin B 1a or ivermectin B 1b , respectively, was mixed with human blood at various concentrations, blood-fed to Anopheles dirus sensu stricto and Anopheles minimus sensu stricto mosquitoes, and mortality was observed for 10 days. The ivermectin B 1a and B 1b ratios from commercially available racemic ivermectin and marketed tablets were assessed by liquid chromatography-mass spectrometry. Results The results revealed that neither the lethal concentrations that kills 50% (LC 50 ) nor 90% (LC 90 ) of mosquitoes differed between racemic ivermectin, ivermectin B 1a or ivermectin B 1b for An. dirus or An. minimus , confirming that the individual ivermectin components have equal mosquito-lethal effects. The relative ratios of ivermectin B 1a and B 1b derived from sourced racemic ivermectin powder were 98.84% and 1.16%, respectively, and the relative ratios for ivermectin B 1a and B 1b derived from human oral ivermectin tablets were 98.55% and 1.45%, respectively. Conclusions The ratio of ivermectin B 1a and B 1b does not influence the Anopheles mosquito-lethal outcome, an ideal study result as the separation of ivermectin B 1a and B 1b components at scale is cost prohibitive. Thus, variations in the ratio of ivermectin B 1a and B 1b between batches and manufacturers, as well as potentially novel formulations for malaria control, should not influence ivermectin mosquito-lethal efficacy.