Evaluation of macrocyclic lactone resistance in gastrointestinal nematodes of first season grazing cattle

Parasitic gastrointestinal nematodes (GIN) are common world-wide among grazing cattle, and cause welfare problems and associated economic losses due to reduced performance of their hosts. In Sweden, the most important GIN include Cooperia oncophora and the more pathogenic Ostertagia ostertagi, which are usually present as mixed infections in first season grazing cattle (FSG). Strategic treatments with anthelmintic drugs remain the principal means of control of helminth infections in grazing livestock in conventional cattle farming. A new challenge for European livestock farmers is the increasing evidence of emerging anthelmintic resistance (AR), which today seems to be an emerging global problem among GIN in cattle. The reasons for AR development, and the mechanisms behind it have not been fully investigated. The primary aim of this thesis was therefore to investigate the effect of one of the most commonly used anthelmintic groups (macrocyclic lactones, ML) against GIN in Swedish cattle, including both dairy and beef herds. An additional aim was to seek an explanation for AR by further characterising worm isolates in vitro and comparing changes in gene expression before and after treatment. Two field trials carried out in consecutive years, one in Northern Europe and one in Sweden, both showed reduced efficacy of ML in FSG, with C. oncophora being the predominant surviving species post anthelmintic treatment. To further investigate this, a controlled pen trial was performed using two isolates collected from the field trials. The results were ambiguous when animals were successfully dewormed according to the standard, but nevertheless several adult worms of C. oncophora survived the treatment. To seek explanations for the varying results, another controlled pen trial was performed in which the pharmacokinetic behaviour of the anthelmintic drug was studied in interaction with concomitant use of dexamethasone (DXM) in FSG. The results showed a significant difference in plasma levels of the anthelmintic drug in combination with DXM. Finally, gene expression regarding P-glycoproteins (PGP), which are transmembrane efflux transporters, was investigated in the same worm isolates before and after ML treatment. Surviving male worms showed a tendency for increased gene expression of putative Con-pgp-9, but amplified fragment length polymorphism (AFLP) testing showed no sign of changes in gene diversity among the surviving worms. The differing results of these studies illustrate the complexity of the AR problem, which poses a great challenge for future research in this area