Shigella flexneri infection: a histopathologic study of colonic biopsies in monkeys infected with virulent and attenuated bacterial strains.

Macaca fascicularis monkeys were orally infected with live virulent Shigella flexneri wild-type strains of either serotype Y (S. flexneri SFL1), 2a (S. flexneri M4243) or 1b (S. flexneri SFL27). Clinical signs of shigellosis varied from mild watery diarrhea (SFL1) to dysentery (M4243, SFL27), with a fatal outcome in two monkeys (SFL27). Colonoscopy showed slight pathologic changes in monkeys infected with SFL1, and pronounced changes in monkeys infected with SFL27. In colonic biopsies the most severe acute inflammation, with surface epithelial erosions and ulcerations, was seen after infection with SFL27, followed by SFL1, and M4243. The live S. flexneri serotype Y vaccine strain SFL114, derived from SFL1 and attenuated because of an inactivated aroD gene and hence auxotrophic for p-aminobenzoic acid, caused no diarrheal illness in 14 monkeys. In colonic biopsies, SFL114 only elicited a slight acute inflammatory reaction. Vaccinated monkeys were protected against clinical disease when challenged with any one of the three virulent S. flexneri wild-type strains. Histopathologically, the acute inflammation was of less intensity than that seen in non-vaccinated monkeys. A good correlation between clinical signs, endoscopic findings and the degree of acute inflammation was demonstrated for monkeys vaccinated with SFL114 and challenged with either SFL1 or SFL27.