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

backgroundThe lack of effective and affordable new environmental tick control products is one of the major challenges to the existing control strategies against the blacklegged tick (Ixodes scapularis), the vector of Lyme disease affecting public health in the United States. Ivermectin is a systemic antiparasitic pesticide 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 the development of a new mouse bait formulation to control immature stages of the blacklegged tick.

methodsThe efficacy of orally delivered 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 adult and nymphal ticks. Mouse baits dosed with two different ivermectin concentrations (24 and 48 ppm) were fed to mice to analyze the pharmacokinetic properties of ivermectin in mouse serum via HPLC analysis. Subsequent tick-challenge trials were conducted to determine the impact of ingested ivermectin mouse bait against larval or nymphal ticks feeding on the mice.

resultsIxodes 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 adult females, as determined by reduced fecal production and engorgement scores. Nymphal capillary feeding experiments were unsuccessful as nymphal ticks in both the control and treatment groups died, likely because of desiccation. In the mouse trials, ivermectin reached peak serum concentrations of 650 ppb and 6715 ppb, respectively, at 2 h after consumption of a single treated pellet containing 80 µg (24 ppm) and 160 µg (48 ppm) ivermectin, respectively. Ivermectin was rapidly depleted from mouse blood with a half-life of < 6 h. Mouse trials showed that ivermectin activity was most effective in controlling larval and nymphal feeding when mice consumed ivermectin-treated bait 24 h before or after tick challenge, with the best results observed in mice fed 48 ppm ivermectin. When larvae were placed 48 h after mice had consumed ivermectin bait, no difference in feeding was observed compared to control.

conclusionsResults from in vitro and in vivo experiments demonstrated the oral efficacy of ivermectin against different developmental stages of the blacklegged tick. The acaricidal effects of ivermectin against I. scapularis nymphs and larvae feeding on white-footed mice, as observed in the mouse trials, may be considered preliminary, and further laboratory and field studies are necessary to validate the utility of an ivermectin-based mouse bait formulation for controlling of immature I. scapularis ticks feeding on mice. To our knowledge, this is the first study to show the oral efficacy and PK analysis of ivermectin in mice. This study found that, although efficacious against tick feeding in the first 24 h, ivermectin has a very short half-life in mice and therefore has a short therapeutic window. This study provides important information for the development of mouse bait to control ticks and tick-borne diseases.