The discovery of Shigella as the etiologic agent of dysentery—a clinical syndrome of fever, intestinal cramps, and frequent passage of small, bloody, mucopurulent stools—is attributed to the Japanese microbiologist Kiyoshi Shiga, who isolated the Shiga bacillus (now known as Shigella dysenteriae type 1) from patients′ stools in 1897 during a large and devastating dysenteryepidemic. Shigella cannot be distinguished from Escherichia coli by DNA hybridization and remains a separate species only on historical and clinical grounds.
Shigella is a nonspore-forming, gram-negative bacterium that, unlike E. coli, is nonmotile and does not produce gas from sugars, decarboxylate lysine, or hydrolyze arginine. Some serovars produce indole, and occasional strains utilize sodium acetate. S.dysenteriae, S. flexneri, S.boydii, and S. sonnei (serogroups A, B, C, and D, respectively) can be differentiated on the basis of biochemical and serologic characteristics. Genome sequencing of E. coli K12, S. flexneri 2a, S. sonnei, S. dysenteriae type 1, and S. boydii has revealed that these species have ∼93% of genes in common. The three major genomic “signatures” of Shigella are (1) a 215-kb virulence plasmid that carries most of the genes required for pathogenicity (particularly invasive capacity); (2) the lack or alteration of genetic sequences encoding products (e.g., lysine decarboxylase) that, if expressed, would attenuate pathogenicity; and (3) in S. dysenteriae type 1, the presence of genes encoding Shiga toxin, a potent cytotoxin.
The human intestinal tract represents the major reservoir of Shigella, which is also found (albeit rarely) in the higher primates. Because excretion of shigellae is greatest in the acute phase of disease, the bacteria are transmitted most efficiently by the fecal-oral route via hand carriage; however, some outbreaks reflect food-borne or waterborne transmission. In impoverished areas, Shigella can be transmitted by flies. The high-level infectivity of Shigella is reflected by the very small inoculum required for experimental infection of volunteers [100 colony-forming units (CFU)], by the very high attack rates during outbreaks in day-care centers (33–73%), and by the high rates of secondary cases among family members of sick children (26–33%). Shigellosis can also be transmitted sexually.
Throughout history, Shigella epidemics have often occurred in settings of human crowding under conditions of poor hygiene—e.g., among soldiers in campaigning armies, inhabitants of besieged cities, groups on pilgrimages, and refugees in camps. Epidemics follow a cyclical pattern in areas such as the Indian subcontinent and sub-Saharan Africa. These devastating epidemics, which are most often caused by S. dysenteriae type 1, are characterized by high attack and mortality rates. In Bangladesh, for instance, an epidemic caused by S. dysenteriae type 1 was associated with a 42% increase in mortality rate among children 1–4 years of age. Apart from these epidemics, shigellosis is mostly an endemic disease, with 99% of cases occurring in the developing world and the highest prevalences in the most impoverished areas, where personal and general hygiene is below standard. S. flexneri isolates predominate in the least developed areas, whereas S. sonnei is more prevalent in economically emerging countries and in the industrialized world.
Prevalence in the Developing World
In a review published under the auspices of the World Health Organization (WHO), the total annual number of cases in 1966–1997 was estimated at 165 million, and 69% of these cases occurred in children <5 years of age. In this review, the annual number of deaths was calculated to range between 500,000 and 1.1 million. More recent data (2000–2004) from six Asian countries indicate that even though the incidence of shigellosis remains stable, mortality rates associated with this disease may have decreased significantly, possibly as a result of improved nutritional status. However, extensive and essentially uncontrolled use of antibiotics, which may also account for declining mortality rates, has increased the rate of emergence of multidrug-resistant Shigella strains. An often-overlooked complication of shigellosis is the short- and long-term impairment of the nutritional status of infected children in endemic areas. Combined with anorexia, the exudative enteropathy resulting from mucosal abrasions contributes to rapid deterioration of the patient's nutritional status. Shigellosis is thus a major contributor to stunted growth among children in developing countries.
Peaking in incidence in the pediatric population, endemic shigellosis is rare in young and middle-aged adults, probably because of naturally acquired immunity. Incidence then increases again in the elderly population.
Prevalence in the Industrialized World
In pediatric populations, local outbreaks occur when proper and adapted hygiene policies are not implemented in group facilities like day-care centers and institutions for the mentally retarded. In adults, as in children, sporadic cases occur among travelers returning from endemic areas, and rare outbreaks of varying size can follow waterborne or food-borne infections.
Pathogenesis and Pathology
Shigella infection occurs essentially through oral contamination via direct fecal-oral transmission, the organism being poorly adapted to survive in the environment. Resistance to low-pH conditions allows shigellae to survive passage through the gastric barrier, an ability that may explain in part why a small inoculum (as few as 100 CFU) is sufficient to cause infection.
The watery diarrhea that usually precedes the dysenteric syndrome is attributable to active secretion and abnormal water reabsorption—a secretory effect at the jejunal level described in experimentally infected rhesus monkeys. This initial purge is probably due to the combined action of an enterotoxin (ShET-1) and mucosal inflammation. The dysenteric syndrome, manifested by bloody and mucopurulent stools, reflects invasion of the mucosa.
The pathogenesis of Shigella is essentially determined by a large virulence plasmid of 214 kb comprising ∼100 genes, of which 25 encode a type III secretion system that inserts into the membrane of the host cell to allow effectors to transit from the bacterial cytoplasm to the host cell cytoplasm (Fig. 154-1). Bacteria are thereby able to invade intestinal epithelial cells by inducing their own uptake after the initial crossing of the epithelial barrier through M cells (the specialized translocating epithelial cells in the follicle-associated epithelium that covers mucosal lymphoid nodules). ...