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Antimicrob. Agents Chemother. doi:10.1128/AAC.00207-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Efficacy of pyrvinium pamoate against Cryptosporidium parvum infection in vitro and in a neonatal mouse model

Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA; Department of Pharmacology and Molecular Sciences, Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Environmental Health Sciences, Division of Environmental Health Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA; Johns Hopkins Center for Water and Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA

^* To whom correspondence should be addressed. Email: dsulliva{at}jhsph.edu.

	Abstract

Effective approved drug therapy for Cryptosporidium in immunocompromised patients does not exist. Here we investigated the non-absorbed antihelminthic drug, pyrvinium pamoate, for growth-inhibition against the intestinal protozoan parasite, Cryptosporidium parvum. Fifty percent growth inhibition in human enterocytic HCT-8 cells by a quantitative alkaline phosphatase immunoassay was 354 nM for pyrvinium. For comparison, in the same assay, fifty percent growth inhibition was 711 µM for paromomycin and 27 µM for chloroquine. We used a neonatal mouse model to measure in vivo anti-Cryptosporidium activity of pyrvinium pamoate. Beginning three days after infection, pyrvinium at 5 mg/kg/day or 12.5 mg/kg/day was administered to the treatment group mice for four or six consecutive days. Nine days after infection, the mice were sacrificed and drug efficacy was determined by comparing numbers of oocysts present in fecal smears of treated versus untreated mice. Trophozoite infection intensity in the ileocaecal intestinal region was also compared using H&E stained histological slides. We observed >90% reduction in infection intensity in the pyrvinium treated mice compared to the untreated controls, along with a substantial reduction in tissue pathology. Based on these results, pyrvinium pamoate is a potential drug candidate for treatment of cryptosporidiosis in immunocompetent and immunocompromised individuals.