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Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model.
Int J Antimicrob Agents. 2014 Apr; 43(4):335-42.IJ

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+Show Affiliations

Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggassstrasse 122, CH-3012 Berne, Switzerland.Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggassstrasse 122, CH-3012 Berne, Switzerland.Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggassstrasse 122, CH-3012 Berne, Switzerland.Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggassstrasse 122, CH-3012 Berne, Switzerland. Electronic address: andrew.hemphill@vetsuisse.unibe.ch.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24646943

Citation

Küster, Tatiana, et al. "Activities of Fenbendazole in Comparison With Albendazole Against Echinococcus Multilocularis Metacestodes in Vitro and in a Murine Infection Model." International Journal of Antimicrobial Agents, vol. 43, no. 4, 2014, pp. 335-42.
Küster T, Stadelmann B, Aeschbacher D, et al. Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model. Int J Antimicrob Agents. 2014;43(4):335-42.
Küster, T., Stadelmann, B., Aeschbacher, D., & Hemphill, A. (2014). Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model. International Journal of Antimicrobial Agents, 43(4), 335-42. https://doi.org/10.1016/j.ijantimicag.2014.01.013
Küster T, et al. Activities of Fenbendazole in Comparison With Albendazole Against Echinococcus Multilocularis Metacestodes in Vitro and in a Murine Infection Model. Int J Antimicrob Agents. 2014;43(4):335-42. PubMed PMID: 24646943.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model. AU - Küster,Tatiana, AU - Stadelmann,Britta, AU - Aeschbacher,Denise, AU - Hemphill,Andrew, Y1 - 2014/02/12/ PY - 2013/11/27/received PY - 2014/01/14/accepted PY - 2014/3/21/entrez PY - 2014/3/22/pubmed PY - 2015/1/13/medline KW - Albendazole KW - Alveolar echinococcosis KW - Chemotherapy KW - Fenbendazole KW - Oxfendazole KW - Ultrastructure SP - 335 EP - 42 JF - International journal of antimicrobial agents JO - Int. J. Antimicrob. Agents VL - 43 IS - 4 N2 - 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. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/24646943/Activities_of_fenbendazole_in_comparison_with_albendazole_against_Echinococcus_multilocularis_metacestodes_in_vitro_and_in_a_murine_infection_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(14)00027-2 DB - PRIME DP - Unbound Medicine ER -