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Background  Outdoor malaria transmission hinders malaria elimination efforts in the Amazon region and novel vector control tools are needed. Ivermectin mass drug administration (MDA) to humans kills wild  Anopheles , targets outdoor-feeding vectors, and can suppress malaria parasite transmission. Laboratory investigations were performed to determine ivermectin susceptibility, sporontocidal effect and inhibition of time to re-feed for the primary Amazonian malaria vector,  Anopheles darlingi .    Methods  To assess ivermectin susceptibility, various concentrations of ivermectin were mixed in human blood and fed to  An. darlingi . Mosquito survival was monitored daily for 7 days and a non-linear mixed effects model with Probit analysis was used to calculate lethal concentrations of ivermectin that killed 50% (LC 50 ), 25% (LC 25 ) and 5% (LC 5 ) of mosquitoes. To examine ivermectin sporonticidal effect,  Plasmodium vivax  blood samples were collected from malaria patients and offered to mosquitoes without or with ivermectin at the LC 50 , LC 25  or LC 5 . To assess ivermectin inhibition of mosquito time to re-feed, concentrations of ivermectin predicted to occur after a single oral dose of 200 μg/kg ivermectin were fed to  An. darlingi . Every day for 12 days thereafter, individual mosquitoes were given the opportunity to re-feed on a volunteer. Any mosquitoes that re-blood fed or died were removed from the study.    Results  Ivermectin significantly reduced  An. darlingi  survivorship: 7-day-LC 50  = 43.2 ng/ml [37.5, 48.6], -LC 25  = 27.8 ng/ml [20.4, 32.9] and -LC 5  = 14.8 ng/ml [7.9, 20.2]. Ivermectin compound was sporontocidal to  P. vivax  in  An. darlingi  at the LC 50  and LC 25  concentrations reducing prevalence by 22.6 and 17.1%, respectively, but not at the LC 5 . Oocyst intensity was not altered at any concentration. Ivermectin significantly delayed time to re-feed at the 4-h (48.7 ng/ml) and 12-h (26.9 ng/ml) concentrations but not 36-h (10.6 ng/ml) or 60-h (6.3 ng/ml).    Conclusions  Ivermectin is lethal to  An. darlingi , modestly inhibits sporogony of  P. vivax , and delays time to re-feed at concentrations found in humans up to 12 h post drug ingestion. The LC 50  value suggests that a higher than standard dose (400-μg/kg) is necessary to target  An. darlingi . These results suggest that ivermectin MDA has potential in the Amazon region to aid malaria elimination efforts.

Ivermectin susceptibility, sporontocidal effect, and inhibition of time to re-feed in the Amazonian malaria vector Anopheles darlingi