Fig. 4

AN7973 efficacy in established and acute murine C. parvum infections. a Effect of AN7973 on established cryptosporidiosis in NOD scid gamma mice. C. parvum (Bunch Grass Farms Iowa isolate) infection was established by oral gavage of ∼10⁵ oocysts and allowed to progress for 7 days prior to once daily oral administration of paromomycin (positive control), or AN7973 at the indicated dosages. Data are the mean and SEM (n = 4 mice per experimental group) of parasite fecal shedding per mg of feces measured by qPCR. Note that no oocyst shedding was detected on day 5 for 3 of 4 mice treated with 25 mg per kg AN7973, and data points are shown at the assay’s limit of detection (0.1 oocysts per mg feces). Asterisk (*) indicates p ≤ 0.02 by one-way ANOVA test with Dunnett’s Method for multiple comparisons. b Effect of AN7973 in an acute, self-resolving IFN-γ knockout mouse model of cryptosporidiosis. C. parvum infection was established by oral gavage of ∼10⁶ C. parvum (University of Arizona Iowa isolate) oocysts followed by daily oral treatment beginning on day 4 post-infection using the indicated dose of AN7973 or clofazimine (positive control). Lines and dosing regimen are color coded as follows: black line (vehicle); gray line (clofazimine 25 mg per kg); purple line (AN7973 5 mg per kg); pink line (AN7973 10 mg per kg); and orange line (AN7973 25 mg per kg). Data are the mean and SEM (n = 4 mice per experimental group) of fecal oocyst shedding as measured by immunostaining and flow cytometry