title: Selection for anthelmintic resistance by macrocyclic lactones in Haemonchus contortus.
abstract: Two morphologically marked strains of Haemonchus contortus, CAVRS (smooth-macrocyclic lactone resistant) and McMaster (linguiform-macrocyclic lactone susceptible), were used to investigate the selection for anthelmintic resistance following exposure to ivermectin (IVM), a non-persistent anthelmintic. and a more persistent anthelmintic, oral moxidectin (MOX). Three types of selection were investigated: (1) selection of resident worms at the time of treatment (Head selection); (2) selection of incoming-larvae post-treatment (Tail selection); and (3) selection of both resident population and incoming larvae (Head + Tail selection). The experimental animals were adult sheep and lambs. In the controls where there was no anthelmintic selection, the proportion of CAVRS in the adult worm population was the same as the proportion in larvae given to both adults and lambs indicating that CAVRS and McMaster H. contortus were equally infective. There was a significant effect of anthelmintic on total worm numbers in adult sheep with MOX treated adults having less worms, but selection type was non-significant. Anthelmintic type had a significant effect on numbers of resistant worms in adult sheep with less resistant worms in the MOX treated groups, but selection type had no effect. Analysis of variance of arcsine-transformed proportions of resistant worms found that the type of anthelmintic had a highly significant effect, with MOX treated adults having a higher proportion of resistant worms, while type of selection was not significant. In the lambs, nil treated controls and IVM Head + Tail and Tail selected groups had similar geometric mean total worm burdens while Head selected had less total worms. In the MOX treated lamb groups the worm burdens were similar within selection type but less than the IVM treated groups. In the lambs, the types of selection that resulted in more resistant worms were IVM Tail, MOX Head + Tail and MOX Tail. Resistant worm numbers were similar in both adult and lamb groups with Head selection by either MOX or IVM. Moxidectin selected out higher proportions of resistant worms than did IVM in the lambs, with Tail and Head + Tail being stronger selectors than Head. Computer simulations were used to estimate the rate at which resistance developed in the field using the information generated in the present study. The anthelmintic treatments used in the simulation followed a strategic parasite control program for H. contortus in which all sheep receive three Closantel (CLS) treatments in summer. all sheep receive a broad-spectrum (BS) drench or capsule at weaning and lambs receive an additional two BS drenches insummer or no further treatment in the case of the capsule. Moxidectin, IVM-capsule and IVM were the broad spectrum anthelmintics simulated. All simulations were run four times assuming high or low efficacy against resident resistant worms and in the presence or absence of CLS resistance. The simulations indicated that the presence of CLS resistance hastened selection for macrocyclic lactone (ML) resistance. While the IVM-capsule will select most rapidly for ML resistance, IVM oral is expected to be least selective. Moxidectin treatment is intermediate, except in simulations with no CLS resistance and when MOX is assumed to be highly effective against resident ML-resistant worms, in which case MOX can be expected to select more slowly than IVM oral treatments.
authors.affiliation: CSIRO Division of Animal Production, Pastoral Research Laboratory, Armidale, NSW, Australia. llejambr@ram.chiswick.anprod.csiro.au
authors.forename: L F
authors.initials: LF
authors.lastname: Le Jambre
authors.forename: R J
authors.initials: RJ
authors.lastname: Dobson
authors.forename: I J
authors.initials: IJ
authors.lastname: Lenane
authors.forename: E H
authors.initials: EH
authors.lastname: Barnes
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D000969:Antinematodal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003198:Computer Simulation; D004351:Drug Resistance / Q000235:genetics; D005243:Feces / Q000469:parasitology; D006188:Haemonchiasis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D006189:Haemonchus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D007559:Ivermectin / Q000494:pharmacology* / Q000627:therapeutic use; D007814:Larva / Q000187:drug effects; D018942:Macrolides; D010270:Parasite Egg Count / Q000662:veterinary; D012756:Sheep; D012757:Sheep Diseases / Q000469:parasitology*
chemical_list: D000900:Anti-Bacterial Agents; D000969:Antinematodal Agents; D018942:Macrolides; D007559:Ivermectin; C027837:moxidectin