Microsporidia cause opportunistic infections in persons with AIDS, organ transplant recipients, children, and travelers. Enterocytozoon bieneusi is the most prevalent microsporidian but attempts to establish a tissue culture system for generating organisms has been unsuccessful. The only nonhuman hosts known for E. bieneusi include pigs and nonhuman primates (eg. Macaca mulatta). Ten SIV-infected rhesus macaques were inoculated orally with E. bieneusi harvested from the stool and duodenal lavage aspirates of human AIDS patients. Spores were detected in stools one week later and continued sporadically for approximately two years or until death of the monkeys, but the inconsistency of spore shedding presently renders this model inadequate for testing antimicrosporidial compounds. However, the monkeys did become infected with E. bieneusi and parasite-associated lesions were identified in the gall bladder, liver, and small intestine. Attempts to infect small animals (eg. gerbils, at hymic mice, immunesuppressed mice) with E. bieneusi also have failed to date. Due to the difficulties in establishing a useful animal model for E. bieneusi, a surrogate microsporidian, Vittaforma corneae is presently being used to develop an animal model for testing lead compounds in vivo. Athymic mice developed wasting (cachexia) and ascites and died 15 - 60 days after intraperitoneal inoculation with 5 x 107 - 1 x 104 V. corneae organisms. Athymic mice infected with 1 x 107 V. corneae and treated with fumagillin survived only a few days longer than non-treated mice but there were statistically significantly fewer parasite-associated lesions in the small intestines, gall bladder, and liver of treated mice. Since fumagillin is toxic in mammals, attempts are underway to obtain fumagillin analogues and related compounds for testing against V. corneae in the murine model. If the simian model can be improved, the effective compounds will then be tested in monkeys, as well. FUNDING NIH; UO1AI0402 (J.A. Shadduck, P.I.); 05/01/96-04/31/00;$277,178 (year 3 total direct; subcontract = approx. 50% of total directs went to RPRC) NIH; NO1-AI-75327 (E.S. Didier, P.I.); 08/15/97-08/14/02; $360,781 (year 2 directs; 100% to RPRC) Venture research funding at TRPRC PUBLICATIONS Abstracts Snowden, K, E.S. Didier, and D. Phalen. 1998. What is the source of Encephalitozoon infections in immunocompromised humans? 49th Ann. Southwest Conference on Disease in Nature Transmissible to Man. College Station, TX (abstract). Snowden, K.F., J.A. Shadduck, and E.S. Didier. 1998. Evaluation of antimicrosporidial therapies using an immunedeficient mouse model. National Cooperative Drug Discovery Groups for the Treatment of Opportunistic Infections (abstract). Snowden, K., D. Phalen, and E.S. Didier. 1998 Where are the reservoirs of human microsporidial infections? Second European Congr. Trop. Med., Liverpool, U.K. (abstract 438) and Amer. J. Trop. Med. Hyg. 59:302 (abstract 554). Green, L.C., L.B. Rogers, P.J. Didier, and E.S. Didier. 1998. Enterocytozoon bieneusi infection immunocompromised rhesus monkeys. Amer. J. Trop. Med. Hyg. 59:332 (abstract 644). Reviews and book chapters Didier, P.J., E.S. Didier, K. Snowden, and J.A. Shadduck. 1998. Encephalitozoonosis. In Infectious Diseases of the Dog and Cat. C.E. Greene (ed.). W.B. Saunders, Philadelphia, PA. pp. 465-469. Didier, E.S., K.A. Snowden, J.A. Shadduck. 1998. The biology of Microsporidian species infecting mammals. Adv. Parasitol. 40:279-316. Didier, E.S. 1998. State-of-the-Art Clinical Article Microsporidiosis. Clin. Infect. Dis. 27:1-7. Didier, P.J., E.S. Didier, and K.F. Snowden. 1998. Microsporidiosis Not just a disease of rabbits. Newsletter Amer. Comm. Lab. Anim. Dis. 19:3-7. Soave, R. and E.S. Didier. 1999. Cryptosporidium and Microsporidium. In Textbook of AIDS Medicine (2nd ed.). T.C. Merigan, J.G. Bartlett, and D. Bolognesi (eds.). Williams and Wilkins, Baltimore, MD. pp. 327-356. Didier, E.S. and G.T. Bessinger. 1999. Host-parasite relationships in microsporidiosis animal models and immunology. In:The Microsporidia and Microsporidiosis. M. Wittner (ed.). American Society for Microbiology, Washington, D.C. pp. 225-257. Didier, E.S. 1999. Immunology of Microsporidiosis. In Contributions to Microbiology. F. Petry (ed). S. Karger AG, Basel, Switzerland (in press). K.F. Snowden, E.S. Didier, J.M. Orenstein, and J.A. Shadduck. 1999. Animal models of human microsporidial infections. In Animal Models. Armed Forces Institute of Pathology, Washington, D.C. (in press).
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