Efficacy of nitazoxanide, tizoxanide and tizoxanide/albendazole sulphoxide combination against Taenia crassiceps cysts

Objectives: Neurocysticercosis is a common parasitic disease in the CNS in humans caused by the metacestode Taenia solium, with high incidence in developing countries. Albendazole is the drug of choice. However, a wide interindividual variability in the response has been reported. In order to evaluate alternative treatment options, the in vitro efficacy of nitazoxanide, its main metabolite tizoxanide as well as the tizoxanide and albendazole sulphoxide combination was tested against Taenia crassiceps cysts. Methods: T. crassiceps cysts were incubated in culture medium containing different concentrations of nitazoxanide, tizoxanide and albendazole sulphoxide (0.037-0.42 mu g/mL). The effect of the tizoxanide and albendazole sulphoxide combination was evaluated in a fixed-concentration ratio (1:1). Isobolographic analyses were used to define the kind of interaction between drugs. Morphological and ultrastructural alterations over the parasite tissue were observed by light and transmission electron microscopy. Results: Nitazoxanide and tizoxanide exhibited cestocidal activity which was time-concentration-dependent. The EC50 values were 0.15, 0.12 and 0.080 mu g/mL for nitazoxanide, tizoxanide and albendazole sulphoxide, respectively. No statistical differences between EC50 values were found, indicating that nitazoxanide and tizoxanide are equally potent as albendazole sulphoxide. The effect of the tizoxanide and albendazole sulphoxide combination was faster than that observed with each drug alone. Isobolographic analysis showed that the effect of the combination was additive. Nitazoxanide and tizoxanide had an effect on the germinal layer, where lipid droplets were found. Nitazoxanide and tizoxanide produced less damage than albendazole sulphoxide on the germinal layer. After the tizoxanide and albendazole sulphoxide combination, a high accumulation of lipid droplets within the germinal layer of the parasite was found. Conclusions: Our results suggest that nitazoxanide in combination with albendazole could be useful for treatment of cysticercosis infections. Additional in vivo studies are required to confirm this hypothesis.