Carotid Taenia solium Oncosphere Infection: A Novel Porcine Neurocysticercosis Model

Abstract

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.

Development of a dose-response model for porcine cysticercosis

“…The review process and the number of articles selected at each stage of the review is shown in Fig 1 . From an initial number of 166 articles, only 8 studies that performed experimental infections were included in this review (including the unpublished study): 2 studies using the “Proglottid” pathway [ 30 , 31 ], 4 studies using the “Eggs” pathway [ 30 , 32 , 36 ], 3 studies using the “Beetles” pathway [ 33 , 34 ], and 2 studies using the “Carotid” pathway [ 35 ].…”

“…Additionally, the collection of T . solium eggs from the proglottids were performed by gentle homogenization [ 30 , 35 ], maceration [ 32 , 36 ] and direct mixing with cattle feces [ 33 , 34 ]. A more detailed description of the experimental designs is available in the publications referenced in Table 1 .…”

“…In this context, the parameters of the exact beta-Poisson for the development of viable cysts through oral inoculation may be the most useful, because this exposure pathway best represents the natural infection pathway, and viable cysts have the potential to produce human taeniasis perpetuating the T . solium life cycle [ 18 , 35 ].…”

“…solium cysticercosis was conducted using indexed literature. In order to have comparable data, this search focused on articles in which the experimental inoculation was carried out through any the following approaches: 1) direct ingestion of gravid proglottids (“Proglottid”) [ 30 , 31 ], 2) inoculation, via an endoesophageal tube, of eggs placed in a gelatin capsule (“Eggs”) [ 30 , 32 , 36 ], 3) direct ingestion of dung beetles previously fed with eggs (“Beetles”) [ 33 , 34 ], and/or 4) inoculation of activated oncospheres (AO) via catheterization of the common carotid artery (“Carotid”) [ 35 ]. These procedures are described in more detail in Table 1 .…”

Effect of Albendazole Treatment in an Experimental Model of Neurocysticercosis-Induced Hydrocephalus

“…12,13 The pathophysiologic mechanisms of NCC-induced hydrocephalus are not fully understood, although experimental models have helped solve some questions regarding leukocyte infiltration and inflammatory reactions-mainly for the parenchymal form of the disease. [14][15][16][17][18][19] Recently, we developed an experimental model of NCC-induced hydrocephalus that reproduces magnetic resonance imaging (MRI) and histologic findings of human NCC. 20 In the present study, we aimed to analyze the effects of albendazole treatment in a rat model of NCC with concomitant hydrocephalus to evalu-ate the correlation between the course of hydrocephalus and animal behavior.…”