In vitro efficacy of triclabendazole and clorsulon against the larval stage of Echinococcus multilocularis

Alveolar echinococcosis (AE) caused by the cestode Echinococcus multilocularis (E. multilocularis) is endemic in wide areas of the Northern hemisphere. Untreated AE progresses and leads to death in more than 90 % of cases. Until the advent of benzimidazoles, no antihelminthic drugs were available to cure AE. Benzimidazoles have greatly improved the prognosis of patients with AE. However, benzimidazoles have only a parasitostatic effect on E. multilocularis. Albendazole (ABZ) must sometimes be withdrawn because of adverse events. Alternative drugs are urgently needed. The antihelminthic triclabendazole (TCZ) and clorsulon (CLS) are more effective than ABZ to cure infections by the liver flukes Fasciola spp. The efficacy of TCZ and CLS was investigated on an in vitro culture of E. multilocularis larval tissue. E. multilocularis vesicles were evaluated for their morphology before and after adding TCZ, TCZ sulfoxide (TCZSX) and CLS to the larval tissue culture. TCZ at the concentrations of 20 mu g/ml culture solution led to maximum vesicle damage within 12 days and of 25 mu g/ml within 13 days, and TCZSX at the concentrations of 20 mu g/ml within 20 days and of 25 mu g/ml within 14 days. Contrary, CLS added at 5, 10 and 15 mu g/ml to culture solution did not lead to any vesicle damage. TCZ is a promising further candidate drug for the treatment of AE.