From field to genetics : anthelmintic resistance in the equine roundworm Parascaris univalens

Sammanfattning: The equine roundworm Parascaris univalens is a common parasite of foals. Most foals show mild clinical symptoms, but large worm burdens can lead to severe colic and even death. Regular treatment with anthelmintic drugs has resulted in resistance development, mainly to ivermectin but also to pyrantel and fenbendazole in sporadic cases. In Sweden, resistance to ivermectin is considered to be widespread.The aim of the thesis was to examine the efficacy of anthelmintic drugs on stud farms in Sweden and Iceland, develop novel models for research and study genetic mechanisms potentially involved in drug metabolism and anthelmintic resistance.Faecal egg count reduction tests showed that resistance to both pyrantel and fenbendazole has emerged on Swedish stud farms, and that ivermectin resistance is common on Icelandic farms. Due to the potentially lethal consequences of infection, this is a serious situation. We developed a novel method to hatch P. univalens eggs in order to use larvae in in vitro experiments to study resistance mechanisms. Quantitative PCR, RNA sequencing and amplicon sequencing were used to study genetic and transcriptomic mechanisms behind anthelmintic resistance in P. univalens. Several genes coding for drug metabolising enzymes, transport proteins and a possible drug target for ivermectin were found to be differentially expressed in P. univalens after exposure to anthelmintic drugs. However, mutations in β-tubulin genes responsible for benzimidazole resistance in many other parasitic nematodes were not present in a fenbendazole-resistant P. univalens population. In conclusion, the current level of resistance in P. univalens has been updated in this thesis, a novel research method has been developed and novel candidate genes for future research have been identified.

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