title: A genetic model describing the evolution of levamisole resistance in Trichostrongylus colubriformis, a nematode parasite of sheep.
abstract: Data from 21 generations of selection on a levamisole-resistant strain of Trichostrongylus colubriformis, either exposed to selection with the anthelmintics levamisole (LEV) or thiabendazole (TBZ), or unexposed, were used to fit a genetic model describing the evolution of LEV resistance in this parasite species. A statistical model describing the dose-response relationship for a mixed population of susceptible and resistant parasite eggs exposed to anthelmintic was fitted to egg-hatch assay data for each generation and for each selection regimen. Estimated parameters from the statistical model provided the input for the genetic model from which were obtained estimates of the relative fitness of susceptible and resistant genotypes under each selection regimen. The experimental data and the genetic models both indicated that, in this parasite strain, LEV resistance was determined by a single dominant gene, and that TBZ selects for LEV susceptibility. A variety of drug alternation programmes was simulated for this genetic system. The programme that minimized the development of LEV resistance involved alternating the drugs (LEV and TBZ) between each worm generation.
mesh_terms: D000818:Animals; D004351:Drug Resistance / Q000235:genetics; D005799:Genes, Dominant; D005838:Genotype; D007978:Levamisole / Q000494:pharmacology*; D008957:Models, Genetic; D015233:Models, Statistical; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy; D013827:Thiabendazole / Q000494:pharmacology; D014253:Trichostrongylosis / Q000188:drug therapy; D014254:Trichostrongylus / Q000187:drug effects* / Q000235:genetics
chemical_list: D007978:Levamisole; D013827:Thiabendazole