Neurocysticercosis (NCC), an infection of the brain by Taenia solium (Ts) cysts, is the most common cause of adult-onset epilepsy in developing countries. Serological testing consists primarily of varying methods to detect antibodies in body fluids and more recently antigen (Ag) detection assays to identify individuals or animals with viable parasites. Antigen assays currently in use employ monoclonal antibodies (mAbs) raised against T. saginata, which have known cross reactivity to animal cestodes but are highly specific in human samples. We produced, characterized and tested 21 mAbs raised against T. solium whole cyst antigens, vesicular fluid or excretory secretory products. Reactivity of the TsmAbs against specific cyst structures was determined using immunofluorescence and immunohistochemistry on histological sections of Ts muscle cysts. Four TsmAbs reacted to vesicular space alone, 9 to the neck and cyst wall, one to the neck and vesicular space and 7 to the neck, cyst wall and vesicular space. An in-house ELISA assay to detect circulating Ts antigen, using the TsmAbs as capture antibodies and a rabbit polyclonal anti-Ts whole cyst antibody as a detector antibody demonstrated that eight of the 21 TsmAbs detected antigens in known NCC-positive human sera and three of these also in urine samples. Reactivity was expressed as normalized ratios of optical densities (OD positive control/OD negative control). Three TsmAbs had ratios >10 and five between 2 and 10. The TsmAbs have potential utility for the diagnosis and post-treatment monitoring of patients with viable NCC infections Disease manifestations in neurocysticercosis (NCC) are frequently due to inflammation of degenerating Taenia solium brain cysts. Exacerbated inflammation post anthelmintic treatment is associated with leakage of the blood brain barrier (BBB) using Evans blue (EB) staining. How well EB extravasation into the brain correlates with magnetic resonance imaging (MRI) using gadolinium (Gd) enhancement as a contrast agent and pericystic inflammation was analyzed in pigs harboring brain cysts of Taenia solium.Three groups of 4 naturally infected pigs were assessed. The first and second groups were treated with both praziquantel plus albendazole and sacrificed two and five days post treatment, respectively. A third untreated group remained untreated. Pigs were injected with EB two hours prior to evaluation by Gd-enhanced T1-MRI, and euthanized. The EB staining for each cyst capsule was scored (EB grades were 0: 0%; 1: up to 50%; 2: over 50% but less than 100%; 3: 100%). Similarly, the Gd enhancement around each cyst was qualitatively and quantitatively scored from the MRI. The extent of pericystic inflammation on histology was scored in increasing severity as IS1, IS2, IS3 and IS4. Grade 3 EB staining and enhancement was only seen in treated capsules. Also, treated groups had higher Gd intensity than the untreated group. Grades of enhancement correlated significantly with Gd enhancement intensity. EB staining was correlated with Gd enhancement intensity and with IS4 in the treated groups. These correlations were stronger in internally located cysts compared to superficial cysts in treated groups.EB staining and Gd enhancement strongly correlate. The intensity of enhancement determined by MRI is a good indication of the degree of inflammation. Similarly, EB staining highly correlates with the degree of inflammation and may be applied to study inflammation in the pig model of NCC.

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18
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2016
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Nash, Theodore E; Ware, JeanAnne M; Mahanty, Siddhartha (2017) Natural History of Patients With Perilesional Edema Around Taenia solium Calcified Granulomas. J Infect Dis 215:1141-1147
Nash, Theodore E; Bustos, Javier A; Garcia, Hector H et al. (2017) Disease Centered Around Calcified Taenia solium Granuloma. Trends Parasitol 33:65-73
Mahanty, Siddhartha; Orrego, Miguel A; Cangalaya, Carla et al. (2017) TNF-? blockade suppresses pericystic inflammation following anthelmintic treatment in porcine neurocysticercosis. PLoS Negl Trop Dis 11:e0006059
Del Brutto, O H; Nash, T E; White Jr, A C et al. (2017) Revised diagnostic criteria for neurocysticercosis. J Neurol Sci 372:202-210
Del Brutto, O H; Nash, T E; White Jr, A C et al. (2017) Revised set of diagnostic criteria for neurocysticercosis (in reply to Garg and Malhotra). J Neurol Sci 373:350-351
Cangalaya, Carla; Bustos, Javier A; Calcina, Juan et al. (2017) Radiological evolution of porcine neurocysticercosis after combined antiparasitic treatment with praziquantel and albendazole. PLoS Negl Trop Dis 11:e0005624
Ware, JeanAnne M; Nash, Theodore E (2016) The Lack of Association of Eosinophilia and Neurocysticercosis at Clinical Presentation: A Retrospective Analysis of Cases Seen at the National Institutes of Health, 1985-2015. Am J Trop Med Hyg 95:1432-1434
Cangalaya, Carla; Bustos, Javier A; Calcina, Juan et al. (2016) Perilesional Inflammation in Neurocysticercosis - Relationship Between Contrast-Enhanced Magnetic Resonance Imaging, Evans Blue Staining and Histopathology in the Pig Model. PLoS Negl Trop Dis 10:e0004869
Williamson, Peter R; Nash, Theodore E; Williamson, Kim C et al. (2016) CNS infections in 2015: emerging catastrophic infections and new insights into neuroimmunological host damage. Lancet Neurol 15:17-9
Paredes, Adriana; Sáenz, Patricia; Marzal, Miguel W et al. (2016) Anti-Taenia solium monoclonal antibodies for the detection of parasite antigens in body fluids from patients with neurocysticercosis. Exp Parasitol 166:37-43

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