Development of a mouse model to determine the systemic activity of potential flea-control compounds

Probe studies were performed to determine if the cat flea (Ctenocephalides felis), the most common ectoparasite of companion animals, will feed on laboratory mice and, if so, to incorporate this into a small animal assay to detect systemically active compounds. Consequently, a protocol was developed which incorporated acepromazine maleate to temporarily sedate various strains of mice and allow fleas a window of time to feed undisturbed. For validation of the model, CD-1 mice were dosed per os with seven known insecticides at 30, 10 and 1mg/kg. Mice were sedated with 0.0125 ml acepromazine maleate intraperitoneally, and infested with fleas. After 2h, fleas were removed, one-third were examined immediately to confirm the occurrence of feeding, and 77% were found to have ingested a blood meal. The remaining fleas were incubated for 24h to determine mortality. Nitenpyram, the active ingredient in Capstar, was highly active (>94%) at 1mg/kg. Selamectin, the active ingredient in Revolution, was very active (86%) at 10mg/kg, but inactive at 1mg/kg. Fipronil, the active ingredient of Frontline Topspot, was very active (83%) at 30 mg/kg, moderately active (54%) at 10mg/kg and inactive at 1mg/kg. Cythioate, the active ingredient in Proban, and nodulisporic acid, a recently discovered oral insecticide, were moderately active (64 and 55%, respectively) at 10mg/kg, but both were inactive at 1mg/kg. Lufenuron and ivermectin exhibited no efficacy at any level tested. These findings suggest that this mouse model can effectively identify systemic flea-control leads and, subsequently, reduce the use of large animals in research.