The therapeutic efficacy of azithromycin and nitazoxanide in the acute pig model of Cryptosporidium hominis.

Sangun Lee,Marvin J Meyers,Saul Tzipori,Melanie Harwood,Mary A Campbell,Don Girouard,Gillian Beamer,Laxmi Yeruva

doi:10.1371/journal.pone.0185906

Sangun Lee, Marvin J Meyers + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0185906

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Journal: PloS one	Publication Date: Oct 3, 2017
Citations: 17	License type: CC BY 4.0

Affiliation: Tufts University, Saint Louis University

Abstract

Recent reports highlighting the global significance of cryptosporidiosis among children, have renewed efforts to develop control measures. We have optimized the gnotobiotic piglet model of acute diarrhea to evaluate azithromycin (AZR), nitazoxanide (NTZ), or treatment with both against Cryptosporidium hominis, the species responsible for most human cases. Piglets, animals reproducibly clinically susceptible to C. hominis, when inoculated with 106 oocysts, developed acute diarrhea with oocyst excretion in feces within 3 days. Ten day-treatment with recommended doses for children, commencing at onset of diarrhea, showed that treatment with AZR or NTZ relieved symptoms early in the treatment compared with untreated animals. Piglets treated with AZR exhibited no reduction of oocyst excretion whereas treatment with NTZ significantly reduced oocyst shedding early, increasing however after 5 days. While treatment with AZR+NTZ led to considerable symptomatic improvement, it had a modest effect on reducing mucosal injury, and did not completely eliminate oocyst excretion. Doubling the dose of AZR and/or NTZ did not improve the clinical outcome, confirming clinical observations that NTZ is only partially effective in reducing duration of diarrhea in children. This investigation confirms the gnotobiotic piglet as a useful tool for drug evaluation for the treatment of cryptosporidiosis in children.

Highlights

The genus Cryptosporidium includes enteric protozoan species which have a worldwide distribution and are found in all classes of vertebrates
Investigations in sub-Saharan Africa [1, 2] concerning cryptosporidiosis have reported that >70% of cases in children are attributed to C. hominis and ~20% to C. parvum, of which >90 are classified as anthroponotic, a unique subspecies that appears to perpetuate within the human populations, and genetically and biologically are different from the bovine C. parvum species
GB piglets challenged with C. hominis TU502 excreted oocysts in feces within 3 days after challenge and continued to do so, regardless of treatment, until they were euthanized at the end of the 10-day treatment experiment

Summary

Introduction

The genus Cryptosporidium includes enteric protozoan species which have a worldwide distribution and are found in all classes of vertebrates. C. parvum and C. hominis are the most common cause of diarrheal illness in humans. Investigations in sub-Saharan Africa [1, 2] concerning cryptosporidiosis have reported that >70% of cases in children are attributed to C. hominis and ~20% to C. parvum, of which >90 are classified as anthroponotic, a unique subspecies that appears to perpetuate within the human populations, and genetically and biologically are different from the bovine C. parvum species. The occurrence of mixed infections as well as with other Cryptosporidium species have been reported infrequently in humans [1, 2].

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