Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
School of Public Health and Management, Universidad Peruana Cayetano Heredia, Lima, Peru.
Am J Trop Med Hyg. 2018 Aug;99(2):380-387. doi: 10.4269/ajtmh.17-0912. Epub 2018 Jun 7.
Neurocysticercosis (NCC), the infection of the human central nervous system (CNS) with larval cysts of causes widespread neurological morbidity. Animal models are crucial for studying the pathophysiology and treatment of NCC. Some drawbacks of current NCC models include differences in the pathogenesis of the model and wild-type parasite, low rates of infection efficiency and lack of reproducibility. We describe a novel porcine model that recreates infection in the CNS with high efficiency. Activated oncospheres, either in a high (45,000-50,000) or low (10,000) dose were inoculated in the common carotid artery of 12 pigs by ultrasound-guided catheterization. Following oncosphere injection, either a high (30 mL) or low (1-3 mL) volume of saline flush was also administered. Cyst burden in the CNS was evaluated independently according to oncosphere dose and flush volume. Neurocysticercosis was achieved in 8/12 (66.7%) pigs. Cyst burden in the CNS of pigs was higher in the high versus the low oncosphere dose category (median: 4.5; interquartile ranges [IQR]: 1-8 and median: 1; IQR: 0-4, respectively) and in the high versus the low flush volume category (median 5.5; IQR: 1-8 and median: 1; IQR: 0-2, respectively), although not statistically different. All cysts in the CNS were viable, whereas both viable and degenerated cysts were found in the musculature. Carotid injection of activated oncospheres in pigs is effective in reproducing NCC. Oncosphere entry into the CNS by way of vasculature mimics wild-type infection, and provides a useful alternative for future investigations on the pathogenesis and antiparasitic treatment of NCC.
神经囊虫病(NCC)是一种人类中枢神经系统(CNS)被幼虫囊感染的疾病,会导致广泛的神经病变。动物模型对于研究 NCC 的病理生理学和治疗方法至关重要。目前 NCC 模型存在一些缺点,包括模型和野生型寄生虫的发病机制存在差异、感染效率低以及缺乏可重复性。我们描述了一种新的猪模型,该模型可以高效地在 CNS 中重现感染。通过超声引导导管,将活性原头蚴以高剂量(45000-50000 个)或低剂量(10000 个)接种到 12 头猪的颈总动脉中。原头蚴注射后,还分别给予高(30 毫升)或低(1-3 毫升)体积的生理盐水冲洗。根据原头蚴剂量和冲洗量,独立评估 CNS 中的囊虫负荷。12 头猪中有 8 头(66.7%)成功感染神经囊虫病。在 CNS 中,高剂量原头蚴组的囊虫负荷高于低剂量原头蚴组(中位数:4.5;四分位距[IQR]:1-8 和中位数:1;IQR:0-4),高冲洗量组的囊虫负荷也高于低冲洗量组(中位数:5.5;IQR:1-8 和中位数:1;IQR:0-2),尽管差异无统计学意义。所有 CNS 中的囊虫均具有活力,而肌肉中既有活力囊虫也有退化囊虫。猪颈动脉内注射活性原头蚴可有效复制 NCC。原头蚴通过血管进入 CNS 的方式模拟了野生型感染,为未来研究 NCC 的发病机制和抗寄生虫治疗提供了有用的替代方法。