In vitro effects of nitazoxanide on Echinococcus granulosus protoscoleces and metacestodes.
OBJECTIVE
Infection of humans and domestic ruminants with the larval stage (metacestode) of Echinococcus granulosus results in cystic echinococcosis (CE). The metacestode causes a space-occupying lesion in visceral organs, most commonly in the liver. Benzimidazole carbamate derivatives, such as mebendazole and albendazole, are currently used for chemotherapeutic treatment of CE. In human patients, benzimidazoles have to be applied in high doses for extended periods of time, and adverse side effects are frequently observed. In order to evaluate alternative treatment options, the in vitro efficacy of nitazoxanide, a broad-spectrum drug used against intestinal parasites and bacteria, was investigated.


METHODS
Freshly isolated E. granulosus protoscoleces were subjected to nitazoxanide treatment (1, 5 and 10 microg/mL), and the effects on parasite viability were monitored by Trypan Blue staining and scanning electron microscopy. Protoscolex cultures were maintained further, until metacestode development took place. Metacestodes were then subjected to nitazoxanide treatment (10 microg/mL), and corresponding effects were visualized by scanning and transmission electron microscopy.


RESULTS
Dose-dependent protoscolex death within a few days of nitazoxanide treatment was observed. Subsequent in vitro culture of drug-treated protoscoleces confirmed the non-viability of parasites, while further cultivation of non-treated protoscoleces for a period of at least 3 months resulted in stage conversion and the formation of small metacestodes 3-4 mm in diameter. Nitazoxanide had a deleterious effect on these metacestodes, which was comparable to that of albendazole.


CONCLUSIONS
Our study indicates a potential for nitazoxanide as an alternative treatment option against CE.
Institute of Parasitology, Faculties of Veterinary Medicine and Medicine, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Swizerland.
Mirjam
M
Walker
Jean François
JF
Rossignol
Paul
P
Torgerson
Andrew
A
Hemphill
D015766:Albendazole / Q000494:pharmacology; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology; D000923:Anticestodal Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004443:Echinococcosis / Q000469:parasitology; D004446:Echinococcus / Q000187:drug effects* / Q000254:growth & development* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009574:Nitro Compounds; D013844:Thiazoles / Q000494:pharmacology*
D000871:Anthelmintics; D000923:Anticestodal Agents; D009574:Nitro Compounds; D013844:Thiazoles; D015766:Albendazole; C041747:nitazoxanide