title: Resistance to prophylactic treatment with macrocyclic lactone anthelmintics in Teladorsagia circumcincta.
abstract: Sixty-four Romney ewe lambs were allocated to 12 groups on the basis of liveweight. Four groups (n=5) were administered oral ivermectin (IVM), 4 (n=6) oral moxidectin (MOX) and the remaining 4 (n=5) controlled-release capsules containing IVM (IVM-CRCs). Nine and 10 days later, the groups within each treatment type were challenged with infective-stage larvae (L3) of 1 of 4 different isolates of Teladorsagia circumcincta (two doses each of 5000 L3). The first of these (S) was known to be anthelmintic-susceptible; the second (OR) was a multiple anthelmintic-resistant strain recovered from the field following therapeutic failure of both ivermectin and moxidectin and subsequently maintained in the laboratory without further anthelmintic selection; the third (R) was derived from OR but had been passaged for five generations indoors with each generation being screened with all three broad-spectrum anthelmintic classes; and the fourth (RxS) was an F1 cross between the R and S isolates. As anticipated, because of its limited residual activity, IVM had no significant effect on the establishment, 9 and 10 days post-treatment, of any of the parasite isolates. In contrast MOX, which has greater residual activity, was highly effective at preventing the establishment of the S isolate but showed no significant effect against the OR, R or RxS isolates. The IVM-CRC was also highly effective at preventing the establishment of the S isolate and furthermore it significantly reduced establishment of both the OR and RxS isolates, although it had no significant effect against the R isolate. The results suggest that with respect to the establishment of T. circumcincta L3s following anthelmintic treatment, macrocyclic lactone (ML) resistance is effectively a dominant trait in the presence of MOX, while it behaves as a partially dominant/recessive trait under treatment with IVM-CRCs. The potential implications of this finding in relation to selection for ML resistance in T. circumcincta are discussed.
authors.affiliation: AgResearch, Grasslands Research Centre, Private Bag 11008, Palmerston North, New Zealand. ian.sutherland@csiro.au
authors.forename: I A
authors.initials: IA
authors.lastname: Sutherland
authors.forename: A E
authors.initials: AE
authors.lastname: Brown
authors.forename: D M
authors.initials: DM
authors.lastname: Leathwick
authors.forename: S A
authors.initials: SA
authors.lastname: Bisset
mesh_terms: D000018:Abomasum / Q000469:parasitology; D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004351:Drug Resistance; D005243:Feces / Q000469:parasitology; D005260:Female; D007411:Intestinal Diseases, Parasitic / Q000188:drug therapy / Q000469:parasitology / Q000517:prevention & control / Q000662:veterinary*; D007559:Ivermectin / Q000627:therapeutic use; D018942:Macrolides / Q000627:therapeutic use; D010028:Ostertagia / Q000254:growth & development* / Q000378:metabolism; D010029:Ostertagiasis / Q000188:drug therapy / Q000469:parasitology / Q000517:prevention & control / Q000662:veterinary*; D010270:Parasite Egg Count; D011897:Random Allocation; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy / Q000469:parasitology* / Q000517:prevention & control*
chemical_list: D000871:Anthelmintics; D003692:Delayed-Action Preparations; D018942:Macrolides; D007559:Ivermectin; C027837:moxidectin