EFFICACY OF NITAZOXANIDE AGAINST CRYPTOSPORIDIUM-PARVUM IN CELL-CULTURE AND IN ANIMAL-MODELS

Nitazoxanide (NTZ), a drug currently being tested in human clinical tr ials for efficacy against chronic cryptosporidiosis,,vas assessed in c ell culture and in two animal models. The inhibitory activity of NTZ w as compared with that of paromomycin (PRM), a drug that is partially e ffective against Cryptosporidium parvum, A concentration of 10 mu g of NTZ/ml (32 mu M) consistently reduced parasite growth in cell culture by more than 90% with little evidence of drug-associated cytotoxicity , in contrast to an 80% reduction produced by PRM at 2,000 mu g/ml (3. 2 mM), In contrast to its efficacy in vitro, NTZ at either 100 or 200 mg/kg of body weight/day for 10 days was ineffective at reducing the p arasite burden in C, parvum-infected, anti-gamma-interferon-conditione d SCID mice. Combined treatment with NTZ and PRM was no more effective than treatment with PRM alone, Finally, NTZ was partially effective a t reducing the parasite burden in a gnotobiotic piglet diarrhea model when given orally for 11 days at 250 mg/kg/day but not at 125 mg/kg/da y, However, the higher dose of NTZ induced a drug-related diarrhea in piglets that might have influenced its therapeutic efficacy, As we hav e previously reported, PRM was effective at markedly reducing the para site burden in piglets at a dosage of 500 mg/kg/day, Our results indic ate that of all of the models tested, the piglet diarrhea model most c losely mimics the partial response to NTZ treatment reported to occur in patients with chronic cryptosporidiosis.