Gruppe Wiedemar

The liver fluke, Fasciola hepatica

The trematode parasite F. hepatica, also called liver fluke, is quite common in ruminants in Switzerland (Frey et al., 2018) and leads to loss of agricultural production. While human infections are relatively rare in Europe, the parasite does significantly affect certain population groups mainly in the Global South and is considered a neglected tropical disease.

F. hepatica undergoes a complex life cycle that involves amphibian snails as intermediate hosts and mammals as final hosts. Mammals get infected by ingesting the environmentally stable cyst form (called metacercariae) of the parasites, usually through consumption of contaminated plants. Once ingested, the parasite hatches from the metacercariae, and the juvenile flukes migrate to and through the liver. By the time the parasites reach the adult stage, they settle in the bile ducts, where they can survive multiple years and multiply sexually. The disease caused by the parasites is called fasciolosis and is characterized by liver inflammation and bile duct obstruction.

Main project: Dissecting resistance mechanisms and identifying new drug targets for the liver fluke Fasciola hepatica, SNSF Ambizione project PZ00P3_216088

Background: Currently, the fight against F. hepatica still heavily relies on drug treatment, whereby triclabendazole is the only marketed drug that acts on the adult as well as on the juvenile stages of the parasites. It is used in human and veterinary medicine. Unfortunately, drug resistance has increasingly been reported from numerous regions around the world. In Switzerland, the spread of resistance is currently unknown, as are the molecular mechanisms of resistance.

Aims: The project has two main objectives, (1) to investigate the occurrence of drug resistance in Swiss F. hepatica populations and to study the mechanisms of resistance, and (2) to look for new molecules that can kill the parasite and investigate new drug targets.

How: For objective (1), we collect and investigate field samples by dissecting infected ruminant livers, collecting adult parasites from the bile ducts and testing their response to triclabendazole exposure. With the collected samples we aim to carry out genomic analyses to learn more about the molecular mechanisms of resistance.

For objective (2), we screen a compound library in juvenile parasites to find molecules with activity in F. hepatica. Active hits are further characterized and investigated mechanistically to gain information about their drug target(s) and mode of action.

The realisation of the project required implementation of different methodologies such as the in vitro cultivation of juvenile and adult parasite stages, the establishment of drug assays in both stages, and the cultivation and infection of the intermediate snail host, Galba truncatula, for parasite reproduction.