Efficacies of albendazole sulfoxide and albendazole sulfone against in vitro-cultivated Echinococcus multilocularis metacestodes

The metacestode stage of Echinococcus multilocularis is the causative agent of alveolar echinococcosis (AE), a parasitic disease affecting the liver, with occasional metastasis into other organs. Benzimidazole carbamate deriv atives such as mebendazole and albendazole are currently used for chemother apeutic treatment of AE. Albendazole is poorly resorbed and is metabolicall y converted to its main metabolite albendazole sulfoxide, which is believed to be the active component, and further to albendazole sulfone. Chemothera py with albendazole has been shown to have a parasitostatic rather than a p arasitocidal effect; it is not effective in all cases, and the recurrence r ate is rather high once chemotherapy is stopped. Thus, development of new m eans of chemotherapy of AE is needed. This could include modifications of b enzimidazoles and elucidiation of the respective biological pathways. In th is study we performed in vitro drug treatment of E. multilocularis metacest odes with albendazole sulfoxide and albendazole sulfone. High-performance l iquid chromatography analysis of vesicle fluids showed that the drugs were taken up rapidly by the parasite. Transmission electron microscopic investi gation of parasite tissues and nuclear magnetic resonance spectroscopy of v esicle fluids demonstrated that albendazole sulfoxide and albendazole sulfo ne had similar effects with respect to parasite ultrastructure and changes in metabolites in vesicle fluids. This study shows that the in vitro cultiv ation model presented here provides an ideal first-round test system for sc reening of antiparasite drugs.