title: Increased burdens of drug-resistant nematodes due to anthelmintic treatment.
abstract: Nine groups of lambs were challenged with 500 drug-resistant (R) Ostertagia circumcincta infective-stage larvae (L3) twice-weekly for 6 weeks; 3 of the groups were also given 500 susceptible (S) L3 and another 3 given 3000 L3 twice-weekly. One week prior to parasite challenge, 1 group of each dose rate was administered ivermectin-capsules (IVM-CRCs). Following challenge, a second group from each dose rate was administered oxfendazole to remove susceptible parasites. The remaining groups received no drug treatment throughout the trial. No significant difference in faecal egg count was observed between the groups. The groups left untreated did not differ significantly in resulting worm burden. However, the percentage of the total L3 challenge recovered as 4th-stage larvae or adult worms demonstrated a density-dependent relationship and declined with increasing challenge. Those groups treated with anthelmintic to remove S worms prior to necropsy also showed density dependency as worm burdens were lower at the highest dose rate. In the groups administered IVM-CRCs, no dose-dependent effect on worm burden was observed. These differences resulted in more worms being present at the highest dose rate in the IVM-CRC-treated animals than in those animals treated orally with anthelmintic. Adult female worms from the IVM-CRC high challenge group were significantly longer and contained more eggs in utero than those in the other high challenge groups. These results demonstrate that where resistance is present, IVM-CRCs can modify the density-dependent regulation of the parasite population, resulting in the acquisition of larger resistant worm burdens than might otherwise be expected. This could accelerate the build-up of resistant worm populations and decrease the time until treatment failure.
authors.affiliation: AgResearch, Grasslands Research Centre, Palmerston North, New Zealand. Ian.Sutherland@agresearch.co.nz
authors.forename: I A
authors.initials: IA
authors.lastname: Sutherland
authors.forename: I C
authors.initials: IC
authors.lastname: Moen
authors.forename: D M
authors.initials: DM
authors.lastname: Leathwick
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005243:Feces / Q000469:parasitology; D005260:Female; D007559:Ivermectin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007814:Larva / Q000187:drug effects / Q000502:physiology; D008297:Male; D010028:Ostertagia / Q000187:drug effects* / Q000502:physiology; D010029:Ostertagiasis / Q000188:drug therapy* / Q000469:parasitology* / Q000662:veterinary; D010270:Parasite Egg Count; D012756:Sheep / Q000469:parasitology*; D012757:Sheep Diseases / Q000188:drug therapy / Q000469:parasitology
chemical_list: D000871:Anthelmintics; D001562:Benzimidazoles; D007559:Ivermectin; C011030:oxfendazole