Sadeghi Mitra, Hosseini Seyed Abdollah, Sarvi Shahabeddin, Ebrahimnejad Pedram, Asgaryan Omran Hossein, Zare Zohre, Gholami Shirzad, Khalilian Alireza, Ahmadi Seyedeh Melika, Hajizadeh Fatemeh, Tork Mostafa, Daryani Ahmad, Aghayan Sargis A
Toxoplasmosis Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
Trop Med Health. 2024 Sep 29;52(1):64. doi: 10.1186/s41182-024-00636-x.
Congenital toxoplasmosis occurs when a pregnant woman becomes infected with Toxoplasma gondii (T. gondii) for the first time. Treatment typically involves antimicrobial medications, with spiramycin commonly used to prevent transmission. However, spiramycin's effectiveness is limited due to poor placental penetration. Clindamycin, another antibiotic, can cross the placenta but reaches the fetus at only half the maternal concentration. Encapsulating the drug in chitosan-coated niosomes (Cs-Nio) could enhance its effectiveness by targeting specific organs and ensuring sustained release. To address the challenges of using clindamycin, a niosome-coated chitosan system was investigated for treating congenital toxoplasmosis caused by the VEG strain of T. gondii in an animal model.
Pregnant mice were infected with VEG strain of T. gondii on the 12th day of pregnancy, followed by treatment with various drugs across six groups. The treatments included chitosan-coated niosomes loaded clindamycin (Cs-Nio-Cli) and other controls. Parasitological evaluations (microscopic examination and real-time PCR), along with histopathological and immunological assessments were conducted to assess treatment efficacy. Finally, statistical analysis was conducted using GraphPad Prism 8.0 and SPSS 26, comparing test and control groups with T test and Mann-Whitney test. A p ≤ 0.05 was considered statistically significant.
The study found that treatment with Cs-Nio-Cli significantly reduced the number of T. gondii cysts in the brain and eyes (97.59% and 92.68%, respectively) compared to the negative control group. It also mitigated inflammatory changes, prevented cell death, and reduced vascular cuffs in the brain. In addition, Cs-Nio-Cli treatment decreased bleeding, placental thrombosis, and inflammatory cell infiltration in the placenta while improving eye tissue health by reducing retinal folds and bleeds. Immunologically, nanoclindamycin treatment resulted in lower TNF-α cytokine levels and higher IL-10 levels, indicating an enhanced anti-inflammatory response.
Although Cs-Nio-Cli demonstrates promise in reducing the transmission of congenital toxoplasmosis and mitigating the effects of congenital toxoplasmosis, additional research is necessary to determine the optimal treatment regimens for the complete eradication of the parasite in the fetus.
先天性弓形虫病发生于孕妇首次感染刚地弓形虫（T. gondii）时。治疗通常涉及抗菌药物，螺旋霉素常用于预防传播。然而，由于胎盘穿透性差，螺旋霉素的有效性有限。另一种抗生素克林霉素可穿过胎盘，但到达胎儿体内的浓度仅为母体浓度的一半。将药物包裹在壳聚糖包被的脂质体（Cs-Nio）中，可通过靶向特定器官并确保持续释放来提高其有效性。为应对使用克林霉素的挑战，研究了一种脂质体包被的壳聚糖系统在动物模型中治疗由刚地弓形虫VEG株引起的先天性弓形虫病的效果。
怀孕小鼠在妊娠第12天感染刚地弓形虫VEG株，随后分六组用不同药物进行治疗。治疗包括壳聚糖包被的负载克林霉素的脂质体（Cs-Nio-Cli）及其他对照。进行寄生虫学评估（显微镜检查和实时PCR）以及组织病理学和免疫学评估以评估治疗效果。最后，使用GraphPad Prism 8.0和SPSS 26进行统计分析，用T检验和曼-惠特尼检验比较试验组和对照组。p≤0.05被认为具有统计学意义。
研究发现，与阴性对照组相比，用Cs-Nio-Cli治疗可显著减少大脑和眼睛中的刚地弓形虫囊肿数量（分别减少97.59%和92.68%）。它还减轻了炎症变化，防止细胞死亡，并减少了大脑中的血管套。此外，Cs-Nio-Cli治疗减少了胎盘出血、胎盘血栓形成和炎症细胞浸润，同时通过减少视网膜褶皱和出血改善了眼组织健康。在免疫学方面，纳米克林霉素治疗导致较低的TNF-α细胞因子水平和较高的IL-10水平，表明抗炎反应增强。
尽管Cs-Nio-Cli在减少先天性弓形虫病传播和减轻先天性弓形虫病影响方面显示出前景，但仍需要进一步研究以确定完全根除胎儿体内寄生虫的最佳治疗方案。
