Pathologic study of a rabbit model for shigellosis

A nonsurgical rabbit model of enteric Shigella infection was developed for studying the pathogenesis and immunology of shigellosis and for evaluating Shigella vaccine candidates. In this model, rabbits are made susceptible to Shigella infection by a pre-inoculation conditioning procedure consisting of a 36-h nonfeeding period, with 250 mg of tetracycline administered in 250 ml of drinking water, 75 mg of cimetidine given intravenously, and two 15-ml doses of 5% sodium bicarbonate given orally immediately before orogastric administration of the bacterial inoculum. Lastly 2 ml of tincture of opium is administered intraperitoneally. With a virulent strain, Shigella flexneri 2a, the clinical and pathologic characteristics of shigellosis in this rabbit model were studied. Twenty hours after oral inoculation of 10(10) bacteria, all six experimental rabbits developed diarrhea and were lethargic or moribund, whereas the four control rabbits inoculated with sterile broth remained healthy. Histologic examination revealed severe, diffuse, necrotizing ileitis with hemorrhage in experimental rabbits, whereas no lesions were found in the controls. Although the major site of necrosis in this rabbit model was the ileum, as opposed to the colon in humans and nonhuman primates, the histologic morphology of the lesion was the same in the various hosts. Because it is relatively inexpensive and convenient, this model should facilitate study of the pathophysiology and immunology of shigellosis, thereby speeding development of oral vaccines, which can be tested in this animal model.