In vitro effects of nitazoxanide on Echinococcus granulosus protoscoleces and metacestodes

Objectives: 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 mug/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 mug/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.