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

Abstract

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 lb (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/7‐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‐vaccina ted 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.

Development of an improved animal model of shigellosis in the adult rabbit by colonic infection with Shigella flexneri 2a

“…The inflammation was usually limited to the superficial lamina propria, with declining severity from the epithelial surface toward the muscularis mucosa. Similar histologic changes due to Shigella infection have been described in the ligated small intestinal loops of rabbits (4) and in the colons of monkeys (21,22). In human shigellosis, the histologic abnormalities of the colon and rectum, as described by different observers (3,10,20,28), are also consistent with our observations in experimentally infected rabbits.…”

Short‐Chain Fatty Acids Improve Clinical, Pathologic, and Microbiologic Features of Experimental Shigellosis

“…This procedure resulted in successful bacterial colonization of the rabbits and development of a dysenteric illness resembling human shigellosis. The characteristics of our model are different from those of the earlier models, which invariably required pretreatment with antimicrobial, antimotility, and toxic agents [24][25][26][27]. These treatments made the animals physiologically unsuitable for therapeutic studies.…”

“…Coded autopsy specimens were examined by a light microscope by an experienced pathologist (M.M.I.). During the histologic evaluation, the severity of inflammation was graded according to a semiquantitative scoring system described by Karnell et al [24] in a monkey model of shigellosis. According to this system, autopsy specimens are classified into normal, mild, moderate, and severe colitis, depending on the severity of inflammatory changes.…”

Evaluation of an intragastric challenge model forShigella dysenteriae1 in rhesus monkeys (Macaca mulatta) for the pre‐clinical assessment ofShigellavaccine formulations

“…Three colonic biopsies were obtained for routine microscopy from each animal on day −3 (which served as baseline), on the day after the monkeys developed clinical signs of dysentery after challenge/re‐challenge. The biopsies were fixed in 10% formalin and processed for conventional histological evaluation using hematoxylin and eosin‐stained sections for a descriptive morphologic diagnosis .…”