Evaluation of nitazoxanide in the treatment of experimental murine neurotoxoplasmosis

Abstract

Toxoplasmosis is a widespread zoonotic disease that poses significant public health concern globally, with neurotoxoplasmosis being a severe complication associated with high mortality rates. The standard therapy for neurotoxoplasmosis involves a combination of sulfadiazine and pyrimethamine, which, despite its efficacy, is often limited by adverse effects leading to treatment discontinuation. This study aimed to evaluate the in vivo efficacy of nitazoxanide in treating neurotoxoplasmosis in mice infected with the Me49 strain. The study comprised two groups: Group I, including subgroups of uninfected, infected and treated with saline, and infected and untreated mice; and Group II, comprising infected mice treated with nitazoxanide at 100 mg/kg/day, nitazoxanide at 150 mg/kg/day, and pyrimethamine combined with sulfadiazine. After 14 days of treatment, the mice were euthanized for organ collection. Histopathological examination of the brains revealed that the highest dose of nitazoxanide reduced parasitic load and cerebral hemorrhages. Biochemical and histopathological analyses of liver and kidney tissues demonstrated toxicological profiles comparable to pyrimethamine and sulfadiazine. However, despite showing efficacy and similar toxicity levels, nitazoxanide treatment was less effective regimen in controlling neurotoxoplasmosis in this experimental model compared to the pyrimethamine and sulfadiazine. Thus, while nitazoxanide presents potential in neurotoxoplasmosis treatment, pyrimethamine combined with sulfadiazine remains the preferred therapeutic choice based on better efficacy observed in this study.