Secondary and primary murine alveolar echinococcosis: combined albendazole/nitazoxanide chemotherapy exhibits profound anti-parasitic activity.

Stettler, Marianne; Rossignol, Jean François; Fink, Renate; Walker, Mirjam; Gottstein, Bruno; Merli, Michael; Theurillat, Regula; Thormann, Wolfgang; Dricot, Eric; Segers, Rudi; Hemphill, Andrew (2004). Secondary and primary murine alveolar echinococcosis: combined albendazole/nitazoxanide chemotherapy exhibits profound anti-parasitic activity. International journal for parasitology, 34(5), pp. 615-624. Elsevier 10.1016/j.ijpara.2004.01.006

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In this study, the efficacies of chemotherapy employing nitazoxanide (NTZ), albendazole (ABZ), and a NTZ/ABZ-combination against alveolar echinococcosis (AE) were investigated in an experimental murine model. Following secondary infection, meaning i.p. injection of 20 Echinococcus multilocularis metacestodes, the drugs were administered by intragastric inoculation on a daily bases for a period of 5 weeks. Treatment was started either immediately on the day of infection, or at 2 months p.i., respectively. Application of the NTZ/ABZ-combination starting at 2 months p.i. was proven to be most effective in terms of reducing parasite weight (from 4.42+/-1.03 to 1+/-0.05 g; P=0.01). Inspection of treated parasites by transmission electron microscopy showed that ABZ- and NTZ-treated metacestode tissues, respectively, were heterogeneous in that both largely intact parasites as well as severely altered metacestodes could be observed. NTZ/ABZ-combination treatment induced the most severe ultrastructural alterations, including massive reduction in length and number of microtriches, severely damaged tegumental architecture, and progressive loss of viability of the germinal layer, associated with encapsulation by host connective tissue. A comparative pharmacokinetic study in mice revealed that the application of ABZ and NTZ in combination resulted in a two- to four-fold increase of albendazole sulfoxide serum levels for the period of 4-8 h following drug uptake compared to application of ABZ alone. In a third experiment, mice were orally infected with E. multilocularis eggs, and treated with NTZ starting at 2 months p.i. This resulted in a significantly lower lesion number in treated versus untreated mice (P=0.01). This investigation indicates the potential value for NTZ and/or a combined ABZ/NTZ chemotherapy against AE.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Laboratory for Clinical Pharmacology

UniBE Contributor:

Gottstein, Bruno; Thormann, Wolfgang and Hemphill, Andrew

Subjects:

600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

0020-7519

Publisher:

Elsevier

Language:

English

Submitter:

Bruno Gottstein

Date Deposited:

23 Jul 2018 09:24

Last Modified:

23 Jul 2018 09:24

Publisher DOI:

10.1016/j.ijpara.2004.01.006

PubMed ID:

15064126

BORIS DOI:

10.7892/boris.118855

URI:

https://boris.unibe.ch/id/eprint/118855

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