Abstract

Toxoplasmosis is a major cause of foodborne disease, congenital complication, and morbidity. There is an urgent need for safe and effective therapies to encounter congenital and persisting toxoplasmosis. The hypothesis was: combination diclazuril plus atovaquone to exert a novel therapeutic synergy to prevent toxoplasmosis syndromes.

Methods: Pregnant dams were treated with diclazuril and atovaquone monotherapy or combination therapy and infected i.p with Toxoplasma tachyzoites.

RESULTS: Infected dams developed severe toxoplasmosis associated syndrome with increases in the abdominal adiposity surrounding uteri, gansterointestinal and other internal organs and excessive weight gain. Numerous organisms along with infiltration of inflammatory cells were detected scattered into adipose tissues. Combination therapy (p < 0.01) and to a lesser extent diclazuril (p < 0.05) protected dams from inflammatory fat and excess weight gains. This was consistent with pancreatitis development in infected dams (versus normal p < 0.05) with infiltration of inflammatory cells, degeneration and necrosis of pancreatic cells followed by the degeneration and loss of islets. Combination and monotherapy protected dams from these inflammatory and pathological aspects of pancreatitis. Infected dams exhibited severe colitis, and colonic tissues significantly shortened in length. Brush border epithelial cells were replaced with infiltration of lymphocytes, granulocytes, and microabscess formations into cryptic microstructures. Combination therapy synergistically preserved colonic structure and normalized pathological damages (p < 0.001) and to a lesser degree diclazuril monotherapy protected dams from colitis (p < 0.05) and gastrointestinal toxoplasmosis. Other complications included severe splenitis (p < 0.001) and hepatitis (p < 0.001) which were normalized with combination therapy.

Conclusion: Combination diclazuril plus atovaquone was safe and with a novel therapeutic synergism protected dams and fetuses from toxoplasmosis.

Document Type

Article

Publication Date

9-15-2014

Notes/Citation Information

Published in Frontiers in Microbiology, v. 5, article 484, p. 1-9.

© 2014 Oz.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Digital Object Identifier (DOI)

http://dx.doi.org/10.3389/fmicb.2014.00484

Funding Information

Dr. Thomas Tobin from Maxwell H. Gluck Equine Center, College of Agriculture, University of Kentucky, provided a portion of funding from Kentucky Science and Technology KSTC 721-RFP-006 . . . . This investigation was supported by the Grant from National Institutes of Health NIH-DE019177 (Helieh S. Oz). University of Kentucky invention property Invention Disclosure is INV11/1773.

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