Title: Current Threat of Triclabendazole Resistance in Fasciola hepatica
Abstract: TCBZ-R in Fasciola hepatica has now been demonstrated on at least 30 properties worldwide. TCBZ-R in F. hepatica is now reported in cattle in Australia and South America. Human infections with TCBZ-resistant F. hepatica have been reported in The Netherlands, Chile, Turkey, and Peru. The coproantigen ELISA may allow an estimate of the intensity of fluke infection in livestock. The mode of action of TCBZ may involve inhibition of adenylate cyclase activity. Genome-wide single nucleotide polymorphism (SNP) analysis to map TCBZ-R in progeny of a genetic cross of parental TCBZ-resistant and TCBZ-susceptible clones has identified several scaffolds within the draft F. hepatica genome sequence associated with the TCBZ-R phenotype. Appearance of resistance to closantel, clorsulon, and nitroxynil emphasises the importance of protecting the efficacy of existing flukicides. A liver fluke vaccine for livestock is a major current area of research. IPM on farms is a key strategy to improve livestock productivity. Triclabendazole (TCBZ) is the only chemical that kills early immature and adult Fasciola hepatica (liver fluke) but widespread resistance to the drug greatly compromises fluke control in livestock and humans. The mode of action of TCBZ and mechanism(s) underlying parasite resistance to the drug are not known. Due to the high prevalence of TCBZ resistance (TCBZ-R), effective management of drug resistance is now critical for sustainable livestock production. Here, we discuss the current status of TCBZ-R in F. hepatica, the global distribution of resistance observed in livestock, the possible mechanism(s) of drug action, the proposed mechanisms and genetic basis of resistance, and the prospects for future control of liver fluke infections using an integrated parasite management (IPM) approach. Triclabendazole (TCBZ) is the only chemical that kills early immature and adult Fasciola hepatica (liver fluke) but widespread resistance to the drug greatly compromises fluke control in livestock and humans. The mode of action of TCBZ and mechanism(s) underlying parasite resistance to the drug are not known. Due to the high prevalence of TCBZ resistance (TCBZ-R), effective management of drug resistance is now critical for sustainable livestock production. Here, we discuss the current status of TCBZ-R in F. hepatica, the global distribution of resistance observed in livestock, the possible mechanism(s) of drug action, the proposed mechanisms and genetic basis of resistance, and the prospects for future control of liver fluke infections using an integrated parasite management (IPM) approach. the purification of a protein based on its ability to bind to a substrate or drug. a chemical drug used to treat a worm infection. the level of specific worm antibody detected by an ELISA assay in the combined milk samples from several dairy cattle. a worm antigen found in faeces. the evaluation of the level of a worm antigen in faeces before and after chemical treatment of the host. the effectiveness of a drug to kill worms in an infected animal. a technique used to measure the level of an antigen or antibody in an animal. the number of worm eggs found in the faeces of an infected animal. the disease caused by infection with Fasciola hepatica or Fasciola gigantica. the evaluation of the level of worm eggs in faeces before and after chemical treatment of an animal. a chemical that kills F. hepatica. set of DNA sequence variations in a chromosome that are inherited together. selection for anthelmintic-resistant roundworms at the time of treatment. a liver fluke aged up to 5-weeks old. the use of a range of methodologies to manage the incidence of parasites in a herd. the analysis of the mass:charge ratio of a molecule. the analysis of metabolic perturbations in a cell upon exposure to drugs. an analytical chemistry technique to determine the content and purity of a sample and its molecular structure. an estimate of the risk of liver fluke disease, based on the calculated evapotranspiration rate and its likely impact on intermediate host snails and shedding of metacercarial cysts. a protein involved in pumping a chemical from a cell. a chemical delivered externally on the back of an animal. the percentage of animals in a herd infected by a parasite. the full protein content of a cell or parasite. the ability of a worm to resist the effects of a chemical normally lethal to it. a nematode parasite. DNA sequence variations at one position in a chromosome. selection for anthelmintic-resistant infective roundworm larvae following treatment. the surface layer of tissue on the liver fluke. tissues in a fluke that produce egg-shell material.