In vitro and in vivo acaricidal properties of orally delivered ivermectin against the blacklegged tick, Ixodes scapularis

Background The lack of effective and affordable new host-targeted tick control products is among major challenges for the existing control strategies against the blacklegged tick ( Ixodes scapularis ), the vector of Lyme disease affecting public health in the United States. Ivermectin is systemic acaricide that has been used successfully to control biting flies and ticks infesting livestock. Ivermectin-treated corn has also been shown to be effective against adult ticks feeding on deer. The goal of this study was to assess acaricidal properties of orally delivered ivermectin against the blacklegged tick, Ixodes scapularis , for development of new mouse bait formulation to control immature stages of the blacklegged tick. Methods The oral toxicity of ivermectin against I. scapularis was evaluated through in vitro capillary feeding tick feeding experiments and in vivo animal trials using laboratory bred white-footed mouse, Peromyscus leucopus . Capillary feeding of adult females and nymphs with different concentrations (18.8–600 ppb) of ivermectin resolved in rabbit blood were performed to ascertain necessary ivermectin plasma levels to kill feeding adult and nymphal ticks. Mouse baits dosed with two different ivermectin concentrations (24 and 48 ppm) were fed to mice to ascertain resulting pharmacokinetic properties of ivermectin in mouse serum via HPLC analysis. Subsequent tick-challenge trials were conducted to determine impacts of ivermectin from ingested the mouse diet against larval or nymphal ticks in the mouse model. Results I. scapularis females capillary-fed with rabbit blood containing 300 and 600 ppb demonstrated a significantly higher tick mortality starting at 72 h after the start of capillary feeding. Such Ivermectin concentrations also significantly reduced blood feeding of the females, as determined by female excretion and engorgement scores. Nymphal capillary feeding experiments were unsuccessful as nymphal in all treatment groups died like in the control group, likely due to desiccation. In the mouse trials, ivermectin reached peak serum concentrations, 650 ppb and 6715 ppb, respectively at 2 hours after consumption of a single treated pellet containing 80 µg and 160 µg ivermectin by mice but was rapidly depleted from mouse blood with a half-life less than six hours. When mice were infested with nymphal and larval ticks at different times relative to mice’s access to diet pellets containing ivermectin (48 ppm) ad libitum, a 45.5% to 100% reduction in the number of blood-fed nymphs and larvae was observed in the treatment groups in comparison to ticks fed on untreated mouse pellets. Conclusions Result of in vitro and in vivo experiments from this study demonstrated the oral toxicity of ivermectin against different developmental stages of the blacklegged tick. Given the acaricidal effects of ivermectin against I. scapularis nymphs and larvae feeding on white-footed mice observed from the mouse trials and how inexpensive ivermectin is, it is feasible to develop new commercial ivermectin-based mouse bait products to add to the tick control toolbox. Further laboratory and field studies are necessary to validate the utility of ivermectin-based mouse-targeted tick control products.