Group Wiedemar

The common liver fluke, Fasciola hepatica

The trematode parasite F. hepatica, also called the common liver fluke, infects the liver of humans and animals. It is distributed worldwide and is also common in ruminants in Switzerland (Frey et al., 2018), where it leads to losses in agricultural production. While human infections occur only sporadically in Europe, the parasite significantly affects certain population groups, mainly in the Global South, and is considered a neglected tropical disease.

The common liver fluke undergoes a complex life cycle that involves lymnaeid snails as intermediate hosts and mammals as definitive hosts. Mammals become infected by ingesting the environmentally stable cyst form of the parasite (called metacercariae), usually through the consumption of contaminated plants; a typical example is wild watercress. Once ingested, the juvenile flukes (approximately 0.2 mm long) hatch in the small intestine and migrate to and through the liver. During the course of infection, the parasites grow (up to 3 cm) and settle in the bile ducts. There, they can survive for multiple years and reproduce sexually. The migration of the parasites through the liver leads to bleeding, liver tissue damage, and inflammation. During the advanced stage of the disease, the parasites can cause obstruction of the bile ducts.

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

Background: As no vaccines are available against the common liver fluke, elimination of the parasites relies heavily on drug treatment. Triclabendazole is the only drug effective against adult and juvenile stages of the parasite and is used in both human and veterinary medicine. Unfortunately, treatment failures and the emergence of drug-resistant parasites have increasingly been reported from numerous regions worldwide and affect animals as well as humans. The occurrence of resistant parasites in Switzerland, as well as the underlying molecular mechanisms of resistance, are currently unknown. Therefore, we are investigating drug resistance in F. hepatica as well as potential new treatment options.

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 identify new molecules that act against the parasite and to explore new drug targets.

How: For objective (1), we collect and investigate field isolates: we obtain adult parasites from naturally infected ruminant livers, and test their sensitivity to triclabendazole. With the collected samples, we carry out genomic analyses to better understand the molecular mechanisms of resistance and the genetics of the parasite more broadly.

For objective (2), we have developed a method to test compounds (molecules) in juvenile parasites. We further characterize molecules with activity against F. hepatica and investigate them mechanistically to gain insight into their drug target(s) and mode of action.