title: Laboratory selection of Haemonchus contortus for resistance to ivermectin.
abstract: The eighth generation of adult Haemonchus contortus, selected by subjecting infected pairs of sheep to suboptimal ivermectin treatment once per generation from parent (P; BBH isolate) through F7 (IV-A; selected isolate), required an approximate 4-fold increase in the ivermectin dose to produce 95% efficacy compared with its contemporary parent isolate. In a dose titration experiment the dose-response curve of the drug pressure-derived isolate, IV-A, was significantly (0.02 less than P less than 0.05) less steep than was the response curve of the parent, BBH, isolate. Potency estimates based upon these nonparallel dose-response curves would not remain constant over a range of efficacy levels but would decrease rapidly at efficacies greater than 95%. Passage of a closed population of the F8 generation of IV-A sequentially through pairs of sheep for an additional 11 generations (F8A-F8K) without additional drug pressure being applied produced no reversion to sensitivity to ivermectin relative to the F7 generation, thus suggesting that the selected "resistance" was stable.
authors.affiliation: Merck Institute for Therapeutic Research, Rahway, New Jersey 07065-0900.
authors.forename: J R
authors.initials: JR
authors.lastname: Egerton
authors.forename: D
authors.initials: D
authors.lastname: Suhayda
authors.forename: C H
authors.initials: CH
authors.lastname: Eary
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005243:Feces / Q000469:parasitology; D006188:Haemonchiasis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary; D006189:Haemonchus / Q000187:drug effects*; D007559:Ivermectin / Q000494:pharmacology* / Q000627:therapeutic use; D010270:Parasite Egg Count / Q000662:veterinary; D011897:Random Allocation; D012044:Regression Analysis; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy / Q000469:parasitology; D014251:Trichostrongyloidea / Q000187:drug effects*
chemical_list: D007559:Ivermectin