MMV665917 cures NOD SCID gamma mice with established cryptosporidiosis. (A) Efficacy of MMV665917 compared with that of paromomycin (positive control) in NSG mice. NSG mice were infected by oral gavage of C. parvum Iowa isolate oocysts. Fecal parasite shedding was detected by qPCR on day 6, after which animals were treated with the indicated drug regimens for 1 week and were then monitored for relapse of infection. Four mice were used per experimental group, except for paromomycin, for which three mice were used. Data are means and standard errors of the means. Asterisks indicate a significant difference (**, P ≤ 0.01), and ns indicates no significant difference (P > 0.05), between the data for each treatment and those for the vehicle control by a nonparametric multiple-comparison Kruskal-Wallis test. BID, twice-daily dosing regimen. (B) Short-term efficacies of nitazoxanide, paromomycin, and clofazimine in the NSG mouse model. NSG mice were infected, and fecal parasite shedding was measured by qPCR, as described for panel A. Beginning 7 days after infection, mice were treated with the indicated drug regimens. Fecal parasite shedding was measured just prior to the initiation of treatment and on the day following completion. Four mice were used per experimental group. Data are means and standard errors of the means. The asterisk indicates a significant difference (P ≤ 0.05) by the Mann-Whitney test.