This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Microsporidia are single-celled parasites that are recognized as causes of opportunistic and emerging infections in persons with AIDS, organ transplant recipients, travelers, and malnourished children. Persons with microsporidiosis usually develop persistent diarrhea, and effective therapies are lacking. Methods: Over 400 compounds were assayed in vitro against two microsporidian species which infect humans, Encephalitozoon intestinalis and Vittaforma corneae. These drugs included protease inhibitors, chitin assembly inhibitors, benzimidazoles which interfere with microtubule assembly, fumagillin-related compounds, fluoroquinolones, and triazines. Compounds that inhibited microsporidia replication by 70% at doses not toxic to the host cells were then tested for their ability to prolong survival in V. corneae-infected athymic mice. Athymic mice (groups of 8 each) were inoculated ip with 1 X 107 V. corneae spores, and drugs were administered beginning one day later. Controls received either parasites only or drug only (toxicity control). Statistically significant increases in survival times were determined by analysis of variance. Results and Discussion: Drugs that significantly (P 0.05) prolonged survival of the V. corneae-infected athymic mice included fumagillin (at 5, 10, or 20 mg/kg sq daily), the fumagillin analogue, TNP-470 (at 20 mg/kg ip daily), doxycycline (at 40 mg/kg ip daily), kanamycin (at 50, 100, or 200 mg/kg ip daily), lomefloxacin (at 100 mg/kg ip daily), norfloxacin (50 and 100 mg/kg ip daily), and gatifloxacin (25 and 50 mg/kg ip daily).
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