EVALUATION OF AN ANIMAL-MODEL SYSTEM FOR CRYPTOSPORIDIOSIS - THERAPEUTIC EFFICACY OF PAROMOMYCIN AND HYPERIMMUNE BOVINE COLOSTRUM-IMMUNOGLOBULIN

Several immunodeficient rodent models currently exist in which persist ent, largely asymptomatic, Cryptosporidium parvum infections can be es tablished. Piglets, in contrast, develop a self-limiting diarrheal ill ness. We have consequently developed an animal model system in which s cid mice were used to screen drugs for inhibitory activity against C. parvum, after which the drags' therapeutic potential was evaluated wit h piglets. Paromomycin and hyperimmune bovine colostrum-immunoglobulin were selected to evaluate this system. C. parvum infections in suckli ng scid mice tended to be associated with villus surfaces, while in we aned and in older scid mice infections were more commonly localized in abscessed crypts. Rates of oocyst shedding in suckling scid mice were 50 to 200 times higher than in weaned mice and therefore made sucklin g mice a considerably more sensitive model for drug testing. Paromomyc in given in high doses over 9 to 10 days was not toxic to either scid mice (3,000 mg/kg of body weight per day) or piglets (500 mg/kg/day). Paromomycin treatment was very effective against villus surface infect ions in suckling mice and considerably less effective against infectio ns in inaccessible sites such as abscessed crypts and stomach pits see n in weaned and adult scid mice. The therapeutic efficacy of paromomyc in in piglets depended on the severity of the diarrheal illness. Mild to moderate diarrhea and infection were cleared after paromomycin trea tment of piglets infected with one C. parvum isolate. However, paromom ycin had no impact on severely affected piglets infected with a second isolate, presumably because of a rapid transit time through the gut. In contrast to paromomycin, hyperimmune bovine colostrum-immunoglobuli n treatment reduced the rate of C. parvum infection moderately in scid mice and only slightly in piglets, again probably because of a rapid transit time through the gut and inactivation in the stomach. It was a lso clear that the impact of effective drugs against C. parvum can be detected within 5 days after the onset of treatment in either model.