In vitro parasiticidal effect of Nitazoxanide against Echinococcus multilocularis metacestodes.

Stettler, Marianne; Fink, Renate; Walker, Mirjam; Gottstein, Bruno; Geary, Timothy G; Rossignol, Jean François; Hemphill, Andrew (2003). In vitro parasiticidal effect of Nitazoxanide against Echinococcus multilocularis metacestodes. Antimicrobial agents and chemotherapy, 47(2), pp. 467-474. American Society for Microbiology

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When humans serve as inadvertent intermediate hosts for Echinococcus multilocularis, disease (alveolar echinococcosis [AE]) may result from the expanding parasite metacestode in visceral organs, mostly in the liver. Benzimidazole carbamate derivatives such as mebendazole and albendazole are used for chemotherapeutic treatment of AE. However, these treatments are, in most cases, parasitistatic rather than parasiticidal. As treatment is discontinued, a recurrence of parasite growth has been observed in many AE patients with nonradical resections. The only curative treatment for AE is radical surgical resection of the parasite tissue and support by chemotherapy. As there is a need for new treatment options for AE, the in vitro efficacy of nitazoxanide (NTZ), a broad-spectrum drug used against intestinal parasites and bacteria, was investigated. We showed that in vitro treatment of E. multilocularis metacestodes with NTZ induced high levels of alkaline phosphatase activity in the medium. Concurrently, distinct morphological and ultrastructural alterations were detected. Most significantly, two distinct types of alterations were observed as soon as after 3 h of NTZ treatment. At first, the drug induced a peripheral output of membranous vesicles from the tegumental membrane into the laminated layer. Simultaneously, germinal layer-associated undifferentiated cells produced large vacuoles filled with lipid-like and often electron-dense membranous segments. Other alterations were observed at later time points, including vacuolization of the germinal layer, accumulation of lipid droplets, and lastly, loss of microtriches and separation of the laminated and germinal layers. The pattern of damage induced by NTZ was different from the alterations earlier observed in albendazole sulfoxide-treated vesicles. The nonviability of NTZ-treated metacestodes was confirmed through bioassay, i.e., inoculation of treated and untreated parasites into mice. These experiments demonstrate the in vitro parasiticidal effect of NTZ on E. multilocularis metacestodes.

Item Type:	Journal Article (Original Article)
Division/Institute:	05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
UniBE Contributor:	Gottstein, Bruno, Hemphill, Andrew
Subjects:	600 Technology > 610 Medicine & health 600 Technology > 630 Agriculture
ISSN:	0066-4804
Publisher:	American Society for Microbiology
Language:	English
Submitter:	Bruno Gottstein
Date Deposited:	23 Jul 2018 08:39
Last Modified:	05 Dec 2022 15:16
PubMed ID:	12543645
URI:	https://boris.unibe.ch/id/eprint/118830