Drug resistance in Fasciola hepatica

Fasciola hepatica (liver fluke) reduces the efficiency of livestock productivity and has a negative impact on ruminant health and welfare. The risk of acute and chronic fasciolosis in sheep and cattle necessitates the use of anthelmintic drugs, to control liver fluke infection and prevent disease. Intensive use of the drug triclabendazole, with its high efficacy against all parasite life cycle stages (>99% from 1 week post infection), has resulted in widespread drug resistance. This raises the possibility that farmers will need to rely on alternative, less effective, anthelmintics e.g., albendazole (≥80% efficacy from 12 weeks post infection). To understand how farmers use anthelmintics we surveyed 72 farmers and triclabendazole accounted for 43.4% (n = 56/129) of all treatment events, with albendazole at 16.3% (n = 21/129). Triclabendazole was used to target liver fluke infection despite known resistance on 36.4% of farms (n = 4/11). To improve detection of resistance to albendazole we validated an albendazole egg hatch test using an isolate known to be albendazole sensitive in vivo (isolate E, 89% reduction in worm burden). The egg hatch test reported a 74.0% ovicidal activity at 0.5 µM (p < 0.001), consistent with our in vivo observations. Four field isolates fell within the equivocal range, suggesting an inability to detect emerging resistance. To investigate the mechanisms underlying triclabendazole resistance, we have explored the role of two candidate genes, ABCB1 gene and the ADP ribosylation factor, focusing on three SNPs potentially involved in triclabendazole resistance (Beesley et al., 2023).