Modelling the development of anthelmintic resistance in cyathostomin parasites: The importance of genetic and fitness parameters.

• A model for the complete cyathostomin lifecycle was constructed. • Multiple mechanisms for the genetics of anthelmintic resistance were incorporated. • Treatment strategies were compared for development of anthelmintic resistance. • The genetics of resistance had a large effect on the rate at which resistance developed. • Different strategies had similar relative ranking regardless of genetic mechanism assumed. Previously described models for the free-living and parasitic phases of the cyathostomin life-cycle were combined into a single model for the complete life-cycle. The model simulates a single free-living population on pasture utilising parasite egg output from the horses and localised temperature and rainfall data to estimate infective larval density on herbage. Multiple horses of different ages are possible, each with an individualised anthelmintic treatment programme. Genotypes for anthelmintic resistance are included allowing for up to three resistance genes with 2 alleles each. Because little is known of the genetics of resistance to anthelmintics in cyathostomins, the first use of this model was to compare the effect of different assumptions regarding the inheritance of resistance on model outputs. Comparisons were made between single and two-gene inheritance, where the heterozygote survival was dominant, intermediate or recessive under treatment, and with or without a fitness disadvantage associated with the resistance mechanism. Resistance developed fastest when the heterozygotes survived anthelmintic treatment (i.e. , were dominant) and slowest when they did not (i.e. , were recessive). Resistance was slower to develop when inheritance was poly-genic compared to a single gene, and when there was a fitness cost associated with the resistance mechanism, although the latter variable was the least influential. Importantly, while these genetic factors sometimes had a large influence on the rate at which resistant genotypes built up in the model populations, their order of ranking was always the same, when different anthelmintic use strategies were compared. Therefore, the described model is a useful tool for evaluating different treatment and management strategies on their potential to select for resistance. [ABSTRACT FROM AUTHOR]