Evaluation of nitazoxanide as a novel drug for the treatment of acute and chronic toxoplasmosis

Abstract

Toxoplasmosis is a widespread, neglected disease with significant morbidity and mortality. In search of an effective treatment, nitazoxanide (NTZ) was evaluated in the treatment of acute and chronic toxoplasmosis in experimental mice. For this purpose, mice were infected with 20 cysts (acute infection model) or 10 cysts (chronic infection model) of Toxoplasma gondii (ME 49 strain). Treated mice received NTZ (at doses of 100 and 150 mg/kg), starting from the third day (acute model) or the fifth week (chronic model) post-infection, which continued for 14 consecutive days. The effects of NTZ were evaluated in comparison to the pyrimethamine/sulfadiazine combination. Evaluation included mortality rates, brain cyst count, inflammatory scoring and immunological studies. The latter included estimation of interferon-gamma (IFN-γ) and induced nitric oxide synthase (iNOS). In the acute infection model, NTZ at 100 and 150 mg/kg significantly reduced the number of brain cysts by 78 and 87% compared to the infected untreated controls and reduced the mortality rate to 24 and 20%, respectively, compared with 44% in the infected untreated control. In the chronic infection model, cyst reduction reached 32 and 38% for 100 and 150 mg/kg NTZ treatments, respectively. NTZ was significantly able to reduce inflammation caused by acute and chronic T. gondii infection with slight necrosis and few infiltrating mononuclear cells. Additionally, the immunological analysis revealed that NTZ significantly increased the production of serum IFN-γ and enhanced iNOS production in brain tissue, suggesting an immunomodulatory role for the drug. Based on the findings of the present study, it can be concluded that NTZ is a potential drug for the treatment of acute and chronic toxoplasmosis.