title: Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model.
abstract: The current chemotherapeutic treatment of alveolar echinococcosis (AE) in humans is based on albendazole and/or mebendazole. However, the costs of treatment, life-long consumption of drugs, parasitostatic rather than parasiticidal activity of chemotherapy, and high recurrence rates after treatment interruption warrant more efficient treatment options. Experimental treatment of mice infected with Echinococcus multilocularis metacestodes with fenbendazole revealed similar efficacy to albendazole. Inspection of parasite tissue from infected and benzimidazole-treated mice by transmission electron microscopy (TEM) demonstrated drug-induced alterations within the germinal layer of the parasites, and most notably an almost complete absence of microtriches. On the other hand, upon in vitro exposure of metacestodes to benzimidazoles, no phosphoglucose isomerase activity could be detected in medium supernatants during treatment with any of these drugs, indicating that in vitro treatment did not severely affect the viability of metacestode tissue. Corresponding TEM analysis also revealed a dramatic shortening/retraction of microtriches as a hallmark of benzimidazole action, and as a consequence separation of the acellular laminated layer from the cellular germinal layer. Since TEM did not reveal any microtubule-based structures within Echinococcus microtriches, this effect cannot be explained by the previously described mechanism of action of benzimidazoles targeting β-tubulin, thus benzimidazoles must interact with additional targets that have not been yet identified. In addition, these results indicate the potential usefulness of fenbendazole for the chemotherapy of AE.
authors.affiliation: Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggassstrasse 122, CH-3012 Berne, Switzerland.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Küster
authors.affiliation: Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggassstrasse 122, CH-3012 Berne, Switzerland.
authors.forename: Britta
authors.initials: B
authors.lastname: Stadelmann
authors.affiliation: Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggassstrasse 122, CH-3012 Berne, Switzerland.
authors.forename: Denise
authors.initials: D
authors.lastname: Aeschbacher
authors.affiliation: Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggassstrasse 122, CH-3012 Berne, Switzerland. Electronic address: andrew.hemphill@vetsuisse.unibe.ch.
authors.forename: Andrew
authors.initials: A
authors.lastname: Hemphill
mesh_terms: D015766:Albendazole / Q000494:pharmacology*; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D000969:Antinematodal Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004445:Echinococcosis, Pulmonary / Q000188:drug therapy; D048210:Echinococcus multilocularis / Q000187:drug effects*; D005260:Female; D005273:Fenbendazole / Q000494:pharmacology*; D005956:Glucose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D021261:Parasitic Sensitivity Tests; D012008:Recurrence; D014404:Tubulin / Q000737:chemistry; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000871:Anthelmintics; D000969:Antinematodal Agents; D014404:Tubulin; D050257:Tubulin Modulators; D005273:Fenbendazole; D005956:Glucose-6-Phosphate Isomerase; D015766:Albendazole
keywords: Albendazole; Alveolar echinococcosis; Chemotherapy; Fenbendazole; Oxfendazole; Ultrastructure