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Antimicrobial Agents and Chemotherapy, August 2001, p. 2256-2262, Vol. 45, No. 8
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.8.2256-2262.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Echinococcus multilocularis Alkaline Phosphatase as a Marker for Metacestode Damage Induced by In Vitro Drug Treatment with Albendazole Sulfoxide and Albendazole Sulfone

Marianne Stettler,¹ Mar Siles-Lucas,¹ Elisabeth Sarciron,² Philippe Lawton,² Bruno Gottstein,¹ and Andrew Hemphill^1,*

Institute of Parasitology, University of Bern, Bern, Switzerland,¹ and Laboratoire de Parasitologie, Université Claude-Bernard, Lyon, France²

Received 9 March 2001/Returned for modification 24 April 2001/Accepted 7 May 2001

Alveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis. The disease affects the human liver and occasionally other organs and is fatal if treatment is unsuccessful. The present chemotherapy of AE is based on the administration of benzimidazole carbamate derivatives, such as mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some cases, parasitostatic rather than parasiticidal, and the recurrence rate is rather high. Therefore, chemotherapy usually involves the lifelong uptake of massive doses of albendazole and new treatment options are urgently needed. In order to avoid costly and time-consuming animal experimentation, a first step in searching for novel parasiticidal compounds could be the in vitro drug screening of novel compounds by employing metacestode cultivation. However, presently used techniques (e.g., transmission electron microscopy) for determination of parasite viability involve costly equipment and time-consuming preparation of rather large amounts of parasite material. We therefore searched for a parasite marker which can be easily traced and the presence or absence of which is indicative of parasite viability. In this study we show that the increase of E. multilocularis alkaline phosphatase activity in culture supernatants during in vitro drug treatment with albendazole derivatives correlates with the progressive degeneration and destruction of the metacestode tissue. The inexpensive and rapid assay presented here will serve as an ideal tool for performing first-round in vitro tests on the efficacy of a large number of antiparasitic compounds.

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^* Corresponding author. Mailing address: Institute of Parasitology, University of Bern, Länggass-Strasse 122, CH-3012 Bern, Switzerland. Phone: (41) 31 6312384. Fax: (41) 31 6312477. E-mail: hemphill{at}ipa.unibe.ch.

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Antimicrobial Agents and Chemotherapy, August 2001, p. 2256-2262, Vol. 45, No. 8
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.8.2256-2262.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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