Published research established that permethrin resistance in lice is caused by amino acid replacements in the alpha-subunit of the voltage-sensitive sodium channel, leading to channel insensitivity and knockdown resistance (kdr). To determine the level and extent of kdr lice, 14,281 lice from 479 human subjects from 138 collection sites in 48 states were analyzed by quantitative sequencing to determine the percent resistance allele frequencies (% RAF), which was overall 98.3 ± 10%, indicating that kdr is widespread. Due to the loss of efficacy of the over-the-counter formulations from kdr, new pediculicidal products (e.g., Natroba, NYDA, Sklice, Ulesfia, etc.) have been registered. To protect these new products from insecticide resistance, resistance mechanisms must be identified proactively and monitored. Using ivermectin, the active ingredient in Sklice, we developed a non-invasive induction assay to proactively identify detoxification genes involved in tolerance as a proof-of-principle approach. One detoxification gene identified was the ATP binding cassette transporter gene, ABCC4. Knockdown of this gene by RNAi significantly increased the sensitivity of lice to ivermectin. The functional properties of PhABCC4 were investigated after expression in Xenopus laevis oocytes. The direct, ATP-dependent, efflux of [3H]-ivermectin from PhABCC4-expressing oocytes was determined to increase over time. Thus, PhABCC4 is likely involved in the phase III xenobiotic metabolism of ivermectin and may play an important role in the eventual evolution of ivermectin resistance in lice. Monitoring of the expression profiles of this putative metabolic resistance gene in field louse populations on a regular basis should provide crucial information on the early stage of ivermectin resistance development, which then could be used in a proactive resistance management program for this valuable new pediculicide.

Overcoming insecticide resistance: Detection and management of insecticide-resistant human lice

254th National Meeting (2017)

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