Triclabendazole and Other Fasciolicides: Resistance of

Fasciolosis is a globally prevalent trematode infection of major veterinary and public-health relevance. Juveniles migrate through liver tissue for weeks before patency, so clinically important infection may occur while faecal egg output is undetectable, complicating control and interpretation of apparent treatment failure. Triclabendazole (TCBZ) remains central because it targets both immature and adult flukes, but sustained use has been accompanied by geographically expanding reports of reduced efficacy and confirmed resistance. Most alternative fasciolicides, such as albendazole, closantel, oxyclozanide, rafoxanide, clorsulon and nitroxynil, are largely adulticidal and used alone or in combinations, yet reports of reduced efficacy/resistance are increasing worldwide. This review summarises drugs in current use and reported resistance status, and outlines a practical pathway for detecting and confirming resistance. We then appraise leading mechanistic hypotheses for TCBZ resistance as a central case study, organised around microtubule-associated phenotypes, reduced effective drug exposure, genetic architecture with tissue context, stress response and detoxification capacity, and we highlight mechanistic gaps for other fasciolicides. Finally, we discuss management implications, including monitoring-guided stewardship, stage-appropriate drug selection, rational combinations, integrated parasite management, and identify near-term priorities for harmonised surveillance, improved diagnostics and tool development. This review updates the resistance landscape and supports practical, monitoring-guided control of fasciolosis.