Experimental infection of conventional neonatal pigs with Clostridium difficile: A new model

Abstract

Objective: To reproduce Clostridium difficile-associated disease (CDAD) using conventional pigs as an animal model. Materials and methods: Nineteen conventional piglets, removed from the sow immediately as they were being born, were enrolled in the study. Neonatal pigs were given pooled colostrum and then transported to a research facility. At approximately 4 hours of age, 13 pigs randomly assigned to treatment groups were each orogastrically inoculated with one of two different swine-origin Clostridium difficile field isolates, and six control pigs were sham-inoculated. All pigs were individually housed and randomly assigned to necropsy at 24, 48, or 72 hours post infection. Results: Commonly observed lesions and indications of CDAD, including mesocolonic edema, toxin detection, diarrhea, neutrophilic infiltration of the colonic and cecal lamina propria, and mucosal ulceration or erosion of the colon and cecum, were observed in challenged pigs. Implications: Data generated in this study provides evidence that this has potential to be an effective challenge model for CDAD. Possible uses for this model include studies of disease pathogenesis and intervention strategies. The described model can be adapted for in vivo studies of human-origin C difficile strains and therapies intended for use in human medicine.