No effective approved
drug therapy exists for
Cryptosporidium infection of immunocompromised patients. Here we investigated the nonabsorbed
anthelmintic drug pyrvinium pamoate for inhibition of the growth of the intestinal protozoan parasite Cryptosporidium parvum. The concentration of
pyrvinium that effected 50% growth inhibition in human enterocytic HCT-8 cells by a quantitative
alkaline phosphatase immunoassay was 354 nM. For comparison, in the same assay, 50% growth inhibition was obtained with 711 microM
paromomycin or 27 microM
chloroquine. We used a neonatal mouse model to measure the anti-Cryptosporidium activity of
pyrvinium pamoate in vivo. Beginning 3 days after
infection,
pyrvinium at 5 or 12.5 mg/kg of
body weight/day was administered to the treatment group mice for 4 or 6 consecutive days. Nine days after
infection, the mice were sacrificed, and
drug efficacy was determined by comparing the numbers of oocysts in the fecal smears of treated versus untreated mice. The intensities of trophozoite
infection in the ileocecal intestinal regions were also compared using
hematoxylin-and-
eosin-stained histological slides. We observed a >90% reduction in
infection intensity in
pyrvinium-treated mice relative to that in untreated controls, along with a substantial reduction in tissue pathology. Based on these results,
pyrvinium pamoate is a potential
drug candidate for the treatment of
cryptosporidiosis in both immunocompetent and immunocompromised individuals.