EVALUATION OF MADURAMICIN AND ALBORIXIN IN A SCID MOUSE MODEL OF CHRONIC CRYPTOSPORIDIOSIS

Two polyether ionophores, maduramicin and alborixin, were evaluated fo r anticryptosporidial activity in a severe combined immune deficient ( SCID) mouse model of cryptosporidiosis. Groups of SCID) mice were inoc ulated with 10(6) oocysts of bovine origin by oral gavage. Maduramicin or alborixin mas administered beginning 4 weeks postinfection at 3 mg /kg of body weight per day. Maduramicin treatment resulted in a 96% re duction in fecal parasite load over the 3-week treatment period (P < 0 .003). This reduction correlated with decreases in tissue parasite loa ds observed in histological sections of the small intestine (P < 0.000 002) and the colon (P < 0.000006). A significant decrease in oocyst sh edding was also observed after a 3-week treatment with alborixin (71% reduction, P < 0.01). Maduramicin was also evaluated in a relapsing mo del of cryptosporidiosis in which the infection was observed to recur after treatments were discontinued. Some toxicity, as demonstrated by weight loss, was observed with both maduramicin and alborixin. Both dr ugs exhibited significant anticryptosporidial activities with concomit ant moderate toxicity. These polyether ionophores should be valuable a s positive controls in compound evaluation studies and as lead compoun ds for chemical optimization (modification).