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Thirty-nine new thiazolide/thiadiazolide compounds were compared with the nitrothiazole nitazoxanide for activity against Cryptosporidium parvum development in HCT-8 cells. Twenty-seven agents exerted ≥90% inhibition. Agents with a lower 50% inhibitory concentration (IC 50 ) than nitazoxanide were either NO 2 or halogen 5 substituted on the thiazole moiety. Other 5 substitutions such as methyl, C 3 H 7 , C 6 H 11 , H, SO 2 CH 3 , and SCH 3 negatively impacted activity. Five-substituted deacetylated analogues exhibited higher IC 50 s than their acetylated counterparts. Halogeno-thiazolide/thiadiazolides may provide valuable nitro-free alternatives to nitazoxanide.

Cryptosporidiumspp. are a cause of self-limited diarrhea in immunocompetent hosts. In immunocompetent rats,Cryptosporidium parvuminfection induced digestive hypersensitivity, a key pathophysiological factor in functional digestive disorders such as irritable bowel syndrome (IBS). In such a rat model, we sought to document whether jejunal hypersensitivity depends onC. parvumisolate and is associated with a mast cell accumulation. Five-day-old rats were orally administered 105oocysts of either Nouzilly (NoI) or Iowa (IoI)C. parvumisolate. NoI-infected rats exhibited the lowest food intake on days 7 and 14 postinfection (p.i.). On day 7 p.i., small intestine villus atrophy, crypt hyperplasia, and inflammatory cell infiltration were prominent in NoI-infected rats, with higher numbers ofCryptosporidiumforms than in IoI-infected rats. Compared to uninfected control rats, jejunal intraepithelial lymphocytes (IELs) were increased only in NoI-infected rats on day 14 p.i. On day 50 p.i., jejunal hypersensitivity to distension was found only in NoI-infected rats; this hypersensitivity is associated with activated mast cell accumulation. The number of mast cells in the jejunal lamina propria was increased from day 36 p.i. in NoI-infected rats and only at day 120 p.i. in IoI-infected rats. Our data suggest that both the severity of infection (weight loss, reduced food intake, villus atrophy, and IEL accumulation) and the onset of a jejunal hypersensitivity after infection in association with an activated mast cell accumulation are isolate dependent and related to NoI infection. This cryptosporidiosis rat model is a relevant model for the study of underlying mechanisms of postinfectious IBS-like symptoms.