The increase in tick resistance to currently available acaricides is a threat to the agricultural animal industry worldwide. For example, the incidence of organophosphate and synthetic pyrethroid resistance among strains of the southern cattle tick Boophilus microplus is rising dramatically in tropical and sub-tropical regions of the world, a trend that poses a potential economic threat to the cattle industry within the United States. To address this challenge, new chemical entities with potent acaricidal activity and novel modes-of-action need to be identified. Currently, none of the available in vitro, whole organism assay systems offers the suitable combination of speed and sensitivity required to rapidly screen large numbers of uncharacterized compounds (e.g., > 500) for acaricidal activity. Therefore, we have developed a tick larval immersion microassay (LIM), based upon the larval immersion test principle, that offers superior sensitivity, a robust capability for screening many compounds in a relatively short period of time, the flexibility to accommodate multiple solvents and detergents, and a minimal requirement of test compound for evaluation. Assay validation involved baseline dose-mortality studies in multiple hard tick species with known acaricides of the organophosphate, synthetic pyrethroid, pyrazole, macrocyclic lactone and carbamate families. Potency measurements yielded quantitative and qualitative information about drug efficacy, with implications for both age-related and species-dependent variables. LY069273, a novel benzimidazole-class compound, was characterized in this assay and found to exhibit acaricidal activity comparable with the organothiophosphate chlorpyrifos. The rationale for using this method to identify, characterize and prioritize compounds for further development will be highlighted.
Species 1: Acari Ixodidae Amblyomma americanum (Lone Star Tick)
Species 2: Acari Ixodidae Boophilus microplus (Cattle Tick)
Species 3: Acari Ixodidae Dermacentor variabilis (American Dog Tick)
Keywords: Acaricide, Bioassay
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