Novel Chemotherapeutical Approaches Against Echinococcosis: A Swiss Perspective

Metacestodes of Echinococcus multilocularis (small fox tapeworm) and E. granulosus sensu lato (dog tapeworm) cause the severe and often incurable diseases alveolar echinococcosis (AE) and cystic echinococcosis (CE). Whereas E. multilocularis is endemic in Switzerland, E. granulosus is not found in animals in Switzerland anymore. Human and animal AE cases are increasing in Switzerland, and so are non-autochthonous human CE cases. Metacestodes consist of an outer laminated layer and an inner germinal layer of living parasite cells. Amongst them, there is a high proportion of undifferentiated stem cells that are refractory to the currently used drugs, benzimidazoles, against AE and CE. Thus, novel drug treatment options are urgently needed. Based on in vitro grown metacestode vesicles of both species, a screening cascade was defined that allows for drug efficacy assessments of repurposed compounds like natural compounds, anti-cancer drugs or anti-infectives. The only identified drugs that so far proofed to be active in subsequent tests in the AE mouse model are benzimidazoles and the anti-malarial mefloquine. In complementary target-based approaches the following potential targets have been identified and studied in vitro: the energy metabolism, in particular the electron transfer chain of the helminth-specific malate dismutation, and the threonine metabolism.