Proof-of-concept study for a long-acting formulation of ivermectin injected to cattle as a complementary malaria vector control tool

Background : Peridomestic animals play a role in maintaining residual transmission of Plasmodium , being alternative blood meal sources for malaria vectors. The blood of animals treated with veterinary formulations of ivermectin show a mosquitocidal effect on malaria vectors, but for a too short period of time to impact Plasmodium transmission. This study proposes to treat cattle with innovative long-acting (six months) injectable formulations of ivermectin as a complementary vector control measure. Methods: The local breeds of cattle were used in two treatment arms (Four cattle injected with two long-acting formulations of ivermectin with the BEPO® technology at the therapeutic dose of 1.2 mg/kg, and two control arms (Four cattle injected with the vehicles of the formulations). The lethality of the formulations was evaluated on 3-5 days old Anopheles coluzzii mosquitoes through direct-skin feeding assays, from one to 210 days after treatments. Formulations’ efficacy was evaluated and compared using Cox proportional hazards survival models, Kaplan-Meier estimates and 4 parameters log-logistic regression on cumulative mortalities. These results were extrapolated to field scenarii using entomological and transmission models, considering different mosquito feeding preferences, hosts abundances, and bed nets uses ratios. Results: Both formulations released mosquitocidal concentrations of ivermectin until 210 days post-treatment (Hazard ratios > 1). The treatments significantly reduced mosquito survival, with the average median survival times of 4-5 days post-feeding. The Lethal Concentrations to kill 50% of the Anopheles (LC50) before they become infectious (10 days after infectious blood meal) were reached until 210 days post injection for both formulations. Modeling showed that administering long-acting ivermectin formulations to calves would significantly decrease Anopheles populations in the fields. The population of infectious vectors may decrease from 35% to 75% depending mostly on the mosquito feeding preference and on the hosts species relative availability. Conclusions: This study shows that, in complement to bed nets, a long-lasting BEPO® formulation of ivermectin injected to cattle could help to decrease field populations of malaria mosquitoes and residual transmission, the impact of this approach being dependant on the field epidemiological context.