Triclabendazole (TCBZ) is the primary treatment for fascioliasis, a global foodborne zoonosis caused by Fasciola hepatica. Widespread resistance to TCBZ (TCBZ-R) in livestock and a rapid rise in resistant human infections are significant concerns. To understand the genetic basis of TCBZ-R, we sequenced the genomes of 99 TCBZ-sensitive (TCBZ-S) and 210 TCBZ-R adult flukes from 146 bovine livers in Cusco, Peru. We identify genomic regions of high differentiation (FST outliers above the 99.9th percentile) that encod genes involved in the EGFR-PI3K-mTOR-S6K pathway and microtubule function. Transcript expression differences are observed in microtubule-related genes between TCBZ-S and -R flukes, both without drug treatment and in response to treatment. Using only 30 SNPs, it is possible to differentiate between TCBZ-S and -R parasites with ≥75% accuracy. Our outlier loci are distinct from t...

Triclabendazole (TCBZ) resistance is an emerging problem in fascioliasis that is not well understood. Studies including small numbers of parasites fail to capture the complexity of susceptibility variations between and within Fasciola hepatica populations. As the first step to studying the complex resistant phenotype–genotype associations, we characterized a large sample of adult F. hepatica with diverging TCBZ susceptibility. We collected parasites from naturally infected livestock slaughtered in the Cusco and Cajamarca regions of Peru. These parasites were exposed to TCBZ sulfoxide (TCBZ.SO) in vitro to determine their susceptibility. We used a motility score to determine the parasite’s viability. We titrated drug concentrations and times to detect 20% non-viable (susceptible conditions) or 80% non-viable (resistant conditions) parasites. We exposed 3348 fully motile parasites to s...

Fascioliasis is a parasitic infection caused by Fasciola spp., primarily affecting ruminant animals. These digenean flatworms cause severe liver damage in their hosts, resulting in substantial economic losses within the livestock industry. Human fascioliasis is an emerging public health concern, with an estimated global prevalence of 2.6 million cases. Infection in humans typically occurs through the ingestion of aquatic vegetation or water contaminated with metacercariae. Triclabendazole (TCBZ) remains the only drug recommended by WHO for the treatment of human fascioliasis and is widely used in livestock. However, the increasing prevalence of TCBZ resistance in livestock, along with reports of TCBZ-resistant human infections, poses a growing challenge to disease control. Although it has been suggested that resistant livestock infections may contribute to the emergence of resistance in ...