In a new study, NIAID scientists and their Peruvian colleagues describe treatment-induced inflammatory responses in pigs with the parasitic brain infection neurocysticercosis. Neurocysticercosis, which is caused by infection with the larval form of the pork tapewormTaenia solium, is the most common cause of adult-onset epilepsy worldwide. The scientists report that blood vessel leakage in and around parasitic cysts rises following antiparasitic treatment and is accompanied by an increase in brain tissue inflammation.
Researchers Investigate Treatment Responses in Pig Model of Parasitic Brain Infection
In a new study, NIAID scientists and their Peruvian colleagues describe treatment-induced inflammatory responses in pigs with the parasitic brain infection neurocysticercosis. They report that blood vessel leakage in and around parasitic cysts rises following antiparasitic treatment and is accompanied by an increase in brain tissue inflammation. The findings appear in the March 16, 2015, online issue of PLOS Neglected Tropical Diseases.
Photo of the surface of the brain of a pig treated with the antiparasitic drug praziquantel showing blue-dyed (blue arrows) and clear (white arrows) cysts. The blue dye indicates disruptions in the blood-brain barrier. Credit: Dr. Cristina Guerra-Giraldez
Neurocysticercosis, a central nervous system infection with the larval form of the pork tapeworm Taenia solium, is the most common cause of adult-onset epilepsy worldwide. The infection results from ingestion of tapeworm eggs, for example, by eating food or drinking water contaminated with feces from a person with an intestinal tapeworm infection. After the eggs hatch, larvae can enter the bloodstream and spread to tissues such as the brain, where they form cysts. Live cysts often do not cause symptoms, while dying cysts trigger an immune response that can lead to seizures and other neurological problems.
Treating neurocysticercosis can be challenging. Antiparasitic drugs damage the cysts, but the degenerating cysts provoke an inflammatory immune response that can worsen a person’s neurological symptoms. A better understanding of the inflammatory responses triggered by antiparasitic treatment would contribute to development of simple, safe, and more effective neurocysticercosis therapies.
Pigs, the natural host of T. solium, are the only other animal besides humans that are readily infected with tapeworm eggs that develop into cysts in the brain. Thus, pigs potentially could serve as models for human neurocysticercosis, offering opportunities to study inflammatory responses near live and dying cysts.
Results of Study
NIAID scientists led by Siddhartha Mahanty, M.D., M.P.H., and their colleagues in Peru investigated brain inflammation following antiparasitic treatment in pigs naturally infected with T. solium cysts. The researchers compared brain tissue from eight pigs treated with the antiparasitic drug praziquantel and five untreated pigs.
The scientists used a blue dye to identify areas in the brain where normally impermeable small blood vessels became leaky, allowing damaging cells and molecules into the brain tissue. These disruptions in the blood-brain barrier were more common in the areas surrounding cysts in treated pigs than in untreated pigs. Further analysis revealed that inflammation in the brain tissues around cysts is more severe with increased blood vessel leakage. The scientists identified increases in levels of several cell-signaling molecules associated with inflammation and immune regulation. In contrast, cysts without blood-brain barrier disruption showed little evidence of inflammation.
The findings indicate that blood vessel leakage around tapeworm cysts in the brain is accompanied by an inflammatory response, and that the proportion of cysts with these characteristics increases following antiparasitic treatment. In addition, the study helps establish the usefulness of a pig model to study neurocysticercosis-related brain inflammation.
The findings from this study suggest that it may be possible to use drugs that block inflammatory responses of a particular kind to prevent inflammation and reduce brain damage during treatment for neurocysticercosis. Future studies using pig models of infection may help scientists identify drugs and biological agents to suppress damaging post-treatment inflammatory responses.
Mahanty S, Orrego MA, Mayta H, Marzal M, Cangalaya C, Paredes A, Gonzales-Gustavson E, Arroyo G, Gonzalez AE, Guerra-Giraldez C, García HH, Nash TE, the Cysticercosis Working Group in Peru. Post-treatment vascular leakage and inflammatory responses around brain cysts in porcine neurocysticercosis. PLOS Neglected Tropical Diseases DOI: 10.1371/journal.pntd.0003577 (2015).