Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, Peru.
Cysticercosis Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru.
PLoS Negl Trop Dis. 2022 Jun 2;16(6):e0010449. doi: 10.1371/journal.pntd.0010449. eCollection 2022 Jun.
Neurocysticercosis (NCC) is the infection of the human central nervous system (CNS) by Taenia solium larvae that cause significant neurological morbidity. Studies on NCC pathophysiology, host-parasite interactions or therapeutic agents are limited by the lack of suitable animal models. We have previously reported that carotid injection of activated T. solium oncospheres directs parasites into the CNS and consistently reproduces NCC. This study assessed the minimal dose required to consistently obtain NCC by intracarotid oncosphere injection and compared antigen and antibody response profiles by dose-group.
METHODS/PRINCIPAL FINDINGS: Three groups of pigs were infected with either 2500 (n = 10), 5000 (n = 11), or 10000 (n = 10) oncospheres. Two pigs died during the study. Necropsy exam at day 150 post-infection (PI) demonstrated viable NCC in 21/29 pigs (72.4%), with higher NCC rates with increasing oncosphere doses (4/9 [44.4%], 9/11 [81.8%] and 8/9 [88.9%] for 2500, 5000, and 10000 oncospheres respectively, P for trend = 0.035). CNS cyst burden was also higher in pigs with increasing doses (P for trend = 0.008). Viable and degenerated muscle cysticerci were also found in all pigs, with degenerated cysticerci more frequent in the 2500 oncosphere dose-group. All pigs were positive for circulating parasite antigens on ELISA (Ag-ELISA) from day 14 PI; circulating antigens markedly increased at day 30 PI and remained high with plateau levels in pigs infected with either 5000 or 10000 oncospheres, but not in pigs infected with 2500 oncospheres. Specific antibodies appeared at day 30 PI and were not different between dose-groups.
CONCLUSION/SIGNIFICANCE: Intracarotid injection of 5000 or more oncospheres produces high NCC rates in pigs with CNS cyst burdens like those usually found in human NCC, making this model appropriate for studies on the pathogenesis of NCC and the effects of antiparasitic treatment.
神经囊尾蚴病（NCC）是人体中枢神经系统（CNS）感染猪带绦虫幼虫引起的重大神经发病率。关于 NCC 病理生理学、宿主-寄生虫相互作用或治疗药物的研究受到缺乏合适动物模型的限制。我们之前曾报道过，颈动脉注射激活的猪带绦虫囊尾蚴可将寄生虫引导至 CNS，并一致复制 NCC。本研究评估了通过颈动脉内囊尾蚴注射获得一致 NCC 所需的最小剂量，并按剂量组比较了抗原和抗体反应谱。
方法/主要发现：三组猪分别用 2500 个（n=10）、5000 个（n=11）或 10000 个（n=10）囊尾蚴感染。在研究过程中有两只猪死亡。感染后 150 天的尸检检查显示 29 只猪中有 21 只（72.4%）有存活的 NCC，随着囊尾蚴剂量的增加，NCC 率也更高（2500、5000 和 10000 个囊尾蚴分别为 4/9 [44.4%]、9/11 [81.8%]和 8/9 [88.9%]，趋势检验 P=0.035）。随着剂量的增加，中枢神经系统囊肿负担也更高（趋势检验 P=0.008）。所有猪在 ELISA（Ag-ELISA）上从感染后第 14 天开始循环寄生虫抗原呈阳性；在感染后第 30 天，循环抗原明显增加，并在感染 5000 或 10000 个囊尾蚴的猪中保持高水平，但在感染 2500 个囊尾蚴的猪中则没有。特异性抗体在感染后第 30 天出现，且在剂量组之间无差异。
结论/意义：颈动脉内注射 5000 个或更多囊尾蚴可使猪的 NCC 率升高，中枢神经系统囊肿负担与人类 NCC 中通常发现的类似，使该模型适合于研究 NCC 的发病机制和抗寄生虫治疗的效果。
