Assessment of candidate anticryptosporidial agents in an immunosuppressed rat model.

Abstract

Cryptosporidium parvum causes life-threatening diarrhea in immunocompromised patients, especially those with AIDS. The efficiency of currently proposed anticryptosporidial therapies is limited or doubtful. In this report, molecular candidates for curative or preventive activity were investigated in an immunocompromised rat model that mimics severe human cryptosporidiosis. No significant anticryptosporidial activity was observed when using sulfadoxine-pyrimethamine, quinacrine, trimethoprim-sulfamethoxazole, bleomycin, elliptinium, daunorubicin, pentamidine, alpha-difluoro-methylornithine, diclazuril or N-methylglucamine. Vitamin A appeared to reduce oocyst shedding. Active agents included sinefungin (2-10 mg/kg/24 h), lasalocid A (2-10 mg/kg/24 h), metronidazole (25-50 mg/kg/24 h), and sulfadimethoxine (10-100 mg/kg/24 h). Sinefungin (10 mg/kg/24 h) and lasalocid A (10 mg/kg/24 h) displayed the highest anticryptosporidial activity.