El-Kowrany Samy Ibrahim, El Ghaffar Amira El-Sayed Abd, Shoheib Zeinab Salah, Mady Rasha Fadly, Gamea Ghada Ahmed Moawad
Medical Parasitology department, Faculty of Medicine - Tanta University.
Medical Parasitology department Faculty of Medicine - Alexandria University.
Acta Trop. 2019 Jul;195:145-154. doi: 10.1016/j.actatropica.2019.04.013. Epub 2019 Apr 12.
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.
弓形虫病是一种广泛存在但被忽视的疾病，具有显著的发病率和死亡率。为寻找有效的治疗方法，对硝唑尼特（NTZ）治疗实验小鼠急性和慢性弓形虫病的效果进行了评估。为此，将小鼠分别感染20个囊肿（急性感染模型）或10个囊肿（慢性感染模型）的刚地弓形虫（ME 49株）。治疗组小鼠从感染后第三天（急性模型）或第五周（慢性模型）开始接受NTZ（剂量为100和150mg/kg），持续给药14天。将NTZ的效果与乙胺嘧啶/磺胺嘧啶联合用药进行比较评估。评估内容包括死亡率、脑囊肿计数、炎症评分和免疫学研究。后者包括干扰素-γ（IFN-γ）和诱导型一氧化氮合酶（iNOS）的测定。在急性感染模型中，与未治疗的感染对照组相比，100和150mg/kg的NTZ分别使脑囊肿数量显著减少78%和87%，死亡率分别降至24%和20%，而未治疗的感染对照组死亡率为44%。在慢性感染模型中，100和150mg/kg NTZ治疗组的囊肿减少率分别达到32%和38%。NTZ能够显著减轻急性和慢性弓形虫感染引起的炎症，仅有轻微坏死和少量浸润的单核细胞。此外，免疫学分析表明，NTZ显著增加血清IFN-γ的产生，并增强脑组织中iNOS的产生，提示该药物具有免疫调节作用。基于本研究的结果，可以得出结论，NTZ是治疗急性和慢性弓形虫病的潜在药物。
