title: The effects of stage-specific selection on the development of benzimidazole resistance in Haemonchus contortus in sheep.
abstract: Resistance to the benzimidazole (BDZ) class of anthelmintics in nematodes of sheep has become a common and global phenomenon. The rate at which the selection process and development of resistance occurs is influenced by a number of factors. Of these, the effects of stage-specific exposures to anthelmintic were investigated with a BDZ-resistant strain of Haemonchus contortus (HCR) over five parasite generations. Sheep were infected at each generation with the HCR strain and were treated with thiabendazole (TBZ), either 5 days post-infection (p.i.) (larval line), 21 days p.i. (adult line), or left untreated (no selection line). Additionally eggs from each generation were exposed to TBZ (egg line). Geometric worm burdens were calculated from post-mortem worm counts, both at the start of the study, and after the final selection studies for each of the selection lines. Egg hatch assays (EHAs) were also conducted throughout the study. All data relating to worm burdens and EHAs for each generation were analysed by linear regression to produce dose titration curves and lethal dose(50) (LD(50)) values for each of the selection lines. Over the five generations, LD(50) values on dose-response were increased and worm survival occurred at higher dose rates of TBZ irrespective of the parasite stage exposed to treatment. A similar picture was seen with ED(50) values, which showed a fluctuating but generally upward trend for each of the three selection lines. In contrast, LD(50) and ED(50) values were decreased in the no selection line, indicating some degree of reversion albeit to levels still considered to be BDZ-resistant.
authors.affiliation: Veterinary Laboratories Agency, New Haw, Addlestone, Surrey KT15 3NB, UK. m.a.taylor@vla.defra.gsi.gov.uk
authors.forename: M A
authors.initials: MA
authors.lastname: Taylor
authors.forename: K R
authors.initials: KR
authors.lastname: Hunt
authors.forename: K L
authors.initials: KL
authors.lastname: Goodyear
mesh_terms: D000375:Aging; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D006188:Haemonchiasis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary; D006189:Haemonchus / Q000187:drug effects* / Q000254:growth & development; D007928:Lethal Dose 50; D016015:Logistic Models; D012641:Selection, Genetic; D012756:Sheep / Q000469:parasitology*; D012757:Sheep Diseases / Q000188:drug therapy / Q000469:parasitology*; D013997:Time Factors
chemical_list: D000871:Anthelmintics; D001562:Benzimidazoles; C031000:benzimidazole