In the United States and Europe, children in day care centers, migrant workers, travelers to developing countries, and residents of nursing homes are most commonly affected. Most Shigella-associated infections and deaths occur in children younger than 5 years of age; in countries in which Shigella is endemic, it is responsible for approximately 10% of all cases of pediatric diarrheal disease and as many as 75% of diarrheal deaths.
Shigella organisms are resistant to the harsh acidic environment of the stomach, which partially explains the very low infective dose. Once in the intestine, organisms are taken up by M (microfold) epithelial cells, which are specialized for sampling and uptake of luminal antigens. After intracellular proliferation, the bacteria escape into the lamina propria. These bacteria then infect small-intestinal and colonic epithelial cells through the basolateral membranes, which express bacterial receptors. Alternatively, luminal shigellae can directly modulate epithelial tight junctions to expose basolateral bacterial receptors. The latter is partly mediated by virulence proteins, some of which are directly injected into the host cytoplasm by a type III secretion system. Some Shigella dysenteriae serotypes also release the Shiga toxin Stx, which inhibits eukaryotic protein synthesis and causes host cell death.
MORPHOLOGYShigella infections are most prominent in the left colon, but the ileum may also be involved, perhapsreflectingtheabundanceofMcellsintheepitheliumoverlyingPeyerpatches.Thehistologicappearanceinearlycasesissimilartothatinotheracuteself-limitedcolitides.Inmoreseverecases,themucosaishemorrhagicandulcerated,andpseudomembranesmaybepresent.PerhapsbecauseofthetropismforMcells,aphthousappearingulcerssimilartothoseseeninCrohndiseasealsomayoccur.Thepotentialforconfusionwithchronicinflammatoryboweldiseaseissubstantial,particularlyifthereisdistortionofcryptarchitecture.
Shigella causes self-limited disease characterized by about 6 days of diarrhea, fever, and abdominal pain.
After an incubation period of 1 to 7 days, the initial watery diarrhea progresses to a dysenteric phase in approximately 50% of patients, and constitutional symptoms can persist for as long as 1 month. A subacute presentation also can develop in a minority of adults. Antibiotic treatment shortens the clinical course and reduces the duration over which organisms are shed in the stool, but anti-diarrheal medications are contraindicated because they can prolong symptoms by delaying bacterial clearance.
Complications of Shigella infection are uncommon and include reactive arthritis, a triad of sterile arthritis, urethritis, and conjunctivitis that preferentially affects HLA-B27– positive men between 20 and 40 years of age. Hemolytic uremic syndrome, which typically is associated with enterohemorrhagic Escherichia coli (EHEC), also may occur after infection with shigellae that secrete Shiga toxin.
Escherichia coli are gram-negative bacilli that colonize the healthy gastrointestinal tract; most are nonpathogenic, but a subset cause human disease. The latter are classified according to morphology, mechanism of pathogenesis, and in vitro behavior (see
Table 15.4 ). Here we summarize their pathogenic mechanisms:
Enterotoxigenic E. coli (ETEC) organisms are the principal cause of traveler’s diarrhea, and are spread by the fecal-oral route. They express a heat-labile toxin (LT) that is similar to cholera toxin and a heat-stable toxin (ST) that increases intracellular cGMP with effects similar to the cAMP elevations caused by LT.