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

The research undertakes a simulation model depicting the entire life cycle of cyathostomin parasites. It focuses on understanding the progression of resistance to anthelmintics under various genetic scenarios and how different treatment approaches influence the selection of resistance among these parasites.

Conceptualization of the Model

• The researchers constructed a comprehensive model integrating two previously described models – one of the free-living phase and another one of the parasitic phase of the cyathostomin life cycle.
• The model anticipates a single free-living population on pasture. It employs parasite egg production data from horses as well as temperature and rainfall data from the locale to calculate the potentially infective larval density on herbage.
• It allows for multiple horses of different ages each having a unique anthelmintic treatment plan to be inputted in the model.

Incorporating Genotypes for Anthelmintic Resistance

• Inclusion of resistance genotypes allows for up to three resistance genes having two alleles each, despite limited knowledge on the genetics of resistance to anthelmintics in cyathostomins.
• The model was initially utilized to analyze the impact of varying assumptions regarding the inheritance of resistance on the model outputs.

Comparative Analysis of Different Assumptions

• The researchers compared single and two-gene inheritance. They did this by assessing situations where the survival rate of heterozygotes was dominant, intermediate or recessive under anthelmintic treatment.
• They also considered scenarios with and without a fitness disadvantage linked to the resistance mechanism.
• It was found that resistance development was fastest when heterozygotes survived anthelmintic treatment (i.e., were dominant) and slowest when they did not (i.e., were recessive).
• Resistance growth pace was slower when inheritance was poly-genic compared to a single gene, and when there was a fitness cost associated with the resistance mechanism. The latter variable was revealed as the least influential, however.

Utility of the Model

• Though the genetic factors sometimes greatly affected the pace at which resistant genotypes built up in the model populations, their ranking order remained the same when different anthelmintic use strategies were compared.
• The model thus appears as a valuable tool to examine a variety of treatment and management strategies and their potential to select for resistance.