Porcine model of neurocysticercosis by intracarotid injection of Taenia solium oncospheres: Dose assessment, infection outcomes and serological responses

Abstract

Background 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.

Concordance between two monoclonal antibody-based antigen detection enzyme-linked immunosorbent assays for measuring cysticercal antigen levels in sera from pigs experimentally infected with Taenia solium and Taenia hydatigena

“…In general, antigen profiles during the follow-up of pigs experimentally infected with T. solium were very similar between assays. We observed high antigen levels in all pigs with viable cysticercosis at day 28 PI and onward, similar to previous studies reported in the literature [ 24 , 30 , 31 ]. Equally, the profile of antigen dynamic in pigs without cysticercosis infection or with only degenerated cysts also showed a similar trend between assays.…”

Concordance between two monoclonal antibody (mAb)-based enzyme-linked immunosorbent assays for the measurement of cysticercal antigen levels in sera of pigs experimentally infected with Taenia solium and Taenia hydatigena

“…In general, antigen pro les during the follow-up of pigs experimentally infected with T. solium were very similar between assays. We observed high antigen levels in all pigs with viable cysticercosis at day 28 PI and onwards, similar to previous studies reported in the literature [24,29,30]. Equally, the pro le of antigen dynamic in pigs without cysticercosis infection or with only degenerated cysts also showed a similar trend between assays.…”

What Causes Seizures in Neurocysticercosis?

“… 63 Recently, Arroyo et al 72 reported on a porcine model in which activated T. solium eggs were administered directly into the common carotid artery, resulting in a more than 66.6% success rate of CNS cyst infection with parasitic loads that resemble that of human NCC. 73 Although this represents a powerful new model system, it is worth noting that it is possible that some aspect of pathology in NCC results from the mismatch between the natural evolution of Taenia larvae to reside in pig tissue and their accidental occurrence in the human brain.…”