Several immunodeficient rodent models currently exist in which persistent, largely asymptomatic, Cryptosporidium
parvum infections can be established. Piglets, in contrast, develop a self-limiting diarrheal illness. We
have consequently developed an animal model system in which scid mice were used to screen drugs for
inhibitory activity against C. parvum, after which the drugs' therapeutic potential was evaluated with piglets.
Paromomycin and hyperimmune bovine colostrum-immunoglobulin were selected to evaluate this system. C.
parvum infections in suckling scid mice tended to be associated with villus surfaces, while in weaned 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 suckling mice a
considerably more sensitive model for drug testing. Paromomycin 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 infections in suckling mice and considerably less effective
against infections in inaccessible sites such as abscessed crypts and stomach pits seen in weaned and adult scid
mice. The therapeutic efficacy of paromomycin in piglets depended on the severity of the diarrheal illness. Mild
to moderate diarrhea and infection were cleared after paromomycin treatment of piglets infected with one C.
parvum isolate. However, paromomycin 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-immunoglobulin 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 also clear that the impact of effective drugs against C. parvum can be detected within 5 days
after the onset of treatment in either model.