Providing information about triclabendazole resistance status influences farmers to change liver fluke control practices

BackgroundReports of disease and production losses associated with Fasciola hepatica, the common liver fluke, have increased in recent years. Resistance to triclabendazole, one of the principal veterinary medicines used to prevent losses, has been reported and is now considered widespread in fluke endemic regions of the UK.MethodsThirteen farmers participated in a trial in 2013 and the triclabendazole resistance status was obtained for each farm. Based on these results, a knowledge exchange programme on fluke control was delivered to nearly 100 farmers in the region. In this follow-up study, 11 farmers involved in the original trial, participated in semistructured in-depth qualitative interviews in July 2017.ResultsOverall, participants identified benefits from participating in the 2013 trial, gaining information about triclabendazole resistance on their farms and knowledge about fluke control. The information on their farm’s resistance status was a driver for changing their liver fluke control programmes. Factors such as habitual and repetitive behaviours, grazing restrictions due to agri-environmental schemes, economic pressures and climate change were identified that could impede or prevent the adoption of new control strategies.ConclusionsThe study highlights the significance of resistance to triclabendazole and the impact of knowledge exchange programmes in changing liver fluke control practices.

Lack of efficacy of triclabendazole against Fasciola hepatica is present on sheep farms in three regions of England, and Wales

The liver fluke Fasciola hepatica is a parasitic trematode that has a major impact on livestock production and human health. Control of F hepatica is difficult and relies on anthelmintics, particularly triclabendazole, due to its efficacy against both adult and juvenile stages of the parasite. Emergence of triclabendazole-resistant F hepatica populations has been reported in a number of countries, including the UK, but the overall prevalence and distribution of triclabendazole resistance is unknown. In this study, the authors established the presence of reduced efficacy of triclabendazole in sheep flocks in England and Wales, using a validated composite faecal egg count reduction test. Seventy-four sheep farms were sampled from Wales, southwest, northwest and northeast England between Autumn 2013 and Spring 2015. F hepatica eggs were detected in samples from 42/74 farms. Evidence of a lack of efficacy of triclabendazole was detected on 21/26 farms on which the faecal egg count reduction test was completed, with faecal egg count reductions ranging from 89 per cent to 0per cent. Regression analysis suggested that both prevalence of F hepatica and lack of efficacy of triclabendazole were spatially correlated, with higher faecal egg counts and lower percentage reductions on farms located in the northwest of England, and Wales. Overall, the results show that reduced efficacy of triclabendazole is present across England and Wales, with a complete lack of therapeutic efficacy observed on 9/26 farms.

Screening the Pathogen Box for Identification of New Chemical Agents with Anti-Fasciola hepatica Activity

ABSTRACT Fascioliasis is an infectious parasitic disease distributed globally and caused by the liver fluke Fasciola hepatica or F. gigantica. This neglected tropical disease affects both animals and humans, and it represents a latent public health problem due to the significant economic losses related to its effects on animal husbandry. For decades, triclabendazole has been the unique anti-Fasciola drug that can effectively treat this disease. However, triclabendazole resistance in fascioliasis has more recently been reported around the world, and thus, the discovery of novel drugs is an urgent need. The aim of this study was to investigate the fasciocidal properties of 400 compounds contained in the Pathogen Box. The first stage of the screening was carried out by measuring the fasciocidal activity on metacercariae at a concentration of 33 μM each compound (the standard dose). Subsequently, the activities of the most active compounds (n = 33) at their 50% inhibitory concentration (IC50) values against metacercariae were assayed, and the results showed that 13 compounds had IC50s of ≤10 μM. The second stage queried the activities of these compounds at 33 μM against adult flukes, with seven of the compounds producing high mortality rates of >50%. Four hit compounds were selected on the basis of their predicted nontoxic properties, and the IC50 values obtained for adult worms were <10 μM; thus, these compounds represented the best fasciocidal compounds tested here. A cytotoxicity assay on four types of cell lines demonstrated that three compounds were nontoxic at their most active concentration. In conclusion, three hit compounds identified in this proof-of-concept study are potential candidates in the discovery of new fasciocidal drugs. Further studies are warranted.

Identification of putative markers of triclabendazole resistance by a genome-wide analysis of genetically recombinant Fasciola hepatica

SUMMARYDespite years of investigation into triclabendazole (TCBZ) resistance in Fasciola hepatica, the genetic mechanisms responsible remain unknown. Extensive analysis of multiple triclabendazole-susceptible and -resistant isolates using a combination of experimental in vivo and in vitro approaches has been carried out, yet few, if any, genes have been demonstrated experimentally to be associated with resistance phenotypes in the field. In this review we summarize the current understanding of TCBZ resistance from the approaches employed to date. We report the current genomic and genetic resources for F. hepatica that are available to facilitate novel functional genomics and genetic experiments for this parasite in the future. Finally, we describe our own non-biased approach to mapping the major genetic loci involved in conferring TCBZ resistance in F. hepatica.