Microsporidia are obligate intracellular parasites that affect a wide range of vertebrate and invertebrate hosts. They are recently recognized pathogens in man and are encountered almost exclusively as opportunistic infections in AIDS patients. The long term objective of this research is to identify new therapeutic modalities and drugs that will prevent, cure or ameliorate human microsporidiosis. There are two specific aims. The first goal is to validate one or more animal models for the study of drugs and combination of drugs and immunomodulators thought likely to be efficacious against these parasites in man. The second is to utilize to use human microsporidia to test the ability of antiparasitic drugs to prevent, ameliorate or cure experimentally induced microsporidial infections in vitro and in vivo. The approach consists of several phases as follows: 1) Utilize drugs for which there already is evidence of efficacy against microsporidia. At least three such drugs are known at present. 2) Use combinations of these drugs to achieve increased therapeutic or preventative efficacy. 3) Test analogues of drugs known to have at least some efficacy against the parasite in order to achieve increased efficacy and/or decreased toxicity. 4) Develop cell culture and animal model systems in which newly discovered drugs can be tested, the results of which will be reliable predictors of efficacy in human beings. 5) Use cell culture systems to gain further insight into mechanisms of drug action. This approach should result in improved therapies for the prevention and/or treatment of human microsporidiosis in AIDS patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI040323-03
Application #
2672862
Study Section
Special Emphasis Panel (ZAI1-VSG-A (60))
Project Start
1996-09-01
Project End
2000-05-31
Budget Start
1998-06-01
Budget End
1999-05-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Texas A&M University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
047006379
City
College Station
State
TX
Country
United States
Zip Code
77845
Snowden, Karen F; Lewis, Barbara C; Hoffman, Jay et al. (2009) Encephalitozoon cuniculi infections in dogs: a case series. J Am Anim Hosp Assoc 45:225-31
Carlisle, M S; Snowden, K; Gill, J et al. (2002) Microsporidiosis in a Gouldian finch (Erythrura [Chloebia] gouldiae). Aust Vet J 80:41-4
Millership, J J; Chappell, C L; Okhuysen, P C et al. (2002) Characterization of a cytosolic aminopeptidase from Encephalitozoon intestinalis. Parasitology 124:1-7
Mittleider, Derek; Green, Linda C; Mann, Victoria H et al. (2002) Sequence survey of the genome of the opportunistic microsporidian pathogen, Vittaforma corneae. J Eukaryot Microbiol 49:393-401
Millership, J J; Didier, E S; Okhuysen, P C et al. (2001) In vitro and in vivo evaluation of aminopeptidase inhibitors as antimicrosporidial therapies. J Eukaryot Microbiol Suppl:95S-98S
Didier, E S (2000) Immunology of microsporidiosis. Contrib Microbiol 6:193-208
Snowden, K F; Logan, K; Phalen, D N (2000) Isolation and characterization of an avian isolate of Encephalitozoon hellem. Parasitology 121 ( Pt 1):14-Sep
Green, L C; LeBlanc, P J; Didier, E S (2000) Discrimination between viable and dead Encephalitozoon cuniculi (Microsporidian) spores by dual staining with sytox green and calcofluor white M2R. J Clin Microbiol 38:3811-4
Didier, E S; Didier, P J; Snowden, K F et al. (2000) Microsporidiosis in mammals. Microbes Infect 2:709-20
Wasson, K; Snowden, K; Didier, E et al. (1999) Rabbit intestinal xenograft model for human Encephalitozoon infections in mice. Lab Anim Sci 49:189-96

Showing the most recent 10 out of 14 publications