Shigellosis: Introduction The discovery of Shigella as the etiologic agent of dysenterya clinical syndrome of fever, intestinal cramps, and

frequent passage of small, bloody, mucopurulent stoolsis 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 dysentery epidemic. Shigella cannot be distinguished from Escherichia coli by DNA hybridization and remains a separate species only on historical and clinical grounds. Definition Shigella is a non-spore-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. Epidemiology 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. Most cases of shigellosis are caused by person-to-person transmission, although some outbreaks reflect contamination of water or food. Shigella can also be transmitted by flies and, given its capacity to survive in foodstuffs, can be a significant cause of food-borne infection. 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 (3373%), and by the high rates of secondary cases among family members of sick children (2633%). Shigellosis can also be transmitted sexually. Clinical Manifestations The presentation and severity of shigellosis depend to some extent on the infecting species but even more on the age and the immunologic and nutritional status of the host. Poverty and a poor hygienic environment are strongly related to the number and severity of diarrheal episodes, especially in children <5 years old. Shigellosis typically evolves through four phases: incubation, watery diarrhea, dysentery, and the postinfectious phase. The incubation period usually lasts 14 days but may be as long as 8 days. Typical initial manifestations are transient fever, limited watery diarrhea, malaise, and anorexia. Signs and symptoms may range from mild abdominal discomfort to severe cramps, diarrhea, fever, vomiting, and tenesmus. The manifestations are usually exacerbated in children, with temperatures up to 40 41C and more severe anorexia and watery diarrhea. Unlike most diarrheal syndromes, dysenteric syndromes do not have dehydration as a major feature. This initial phase may represent the only clinical manifestation of shigellosis, especially in developed countries. Otherwise, dysentery follows within hours or days and is characterized by small volumes of bloody mucopurulent stools with increased tenesmus and abdominal cramps. At this stage, Shigella produces acute colitis involving mainly the distal colon and the rectum. Endoscopy demonstrates an edematous and hemorrhagic mucosa, with ulcerations and possibly overlying exudates resembling pseudomembranes. The extent of the lesions correlates with the number and frequency of stools and with the degree of protein loss by exudative mechanisms. Most episodes are self-limited and resolve without treatment in 1 week. With appropriate treatment, recovery takes place within a few days to a week, with no sequelae. Salmonellosis: Introduction Bacteria of the genus Salmonella are highly adapted for growth in both humans and animals and cause a wide spectrum of disease. The growth of serotypes S. Typhi and S. Paratyphi is restricted to human hosts, in whom these organisms cause enteric

(typhoid) fever. The remaining serotypes (nontyphoidal Salmonella, or NTS) can colonize the gastrointestinal tracts of a broad range of animals, including mammals, reptiles, birds, and insects. More than 200 serotypes are pathogenic to humans, in whom they often cause gastroenteritis and can be associated with localized infections and/or bacteremia. Pathogenesis All Salmonella infections begin with ingestion of organisms in contaminated food or water. The infectious dose is 103106 colony-forming units. Conditions that decrease either stomach acidity (an age of <1 year, antacid ingestion, or achlorhydric disease) or intestinal integrity (inflammatory bowel disease, prior gastrointestinal surgery, or alteration of the intestinal flora by antibiotic administration) increase susceptibility to Salmonella infection. Clinical Manifestations Gastroenteritis Infection with NTS most often results in gastroenteritis indistinguishable from that caused by other enteric pathogens. Nausea, vomiting, and diarrhea occur 648 h after the ingestion of contaminated food or water. Patients often experience abdominal cramping and fever (3839C; 100.5102.2F). Diarrheal stools are usually loose, nonbloody, and of moderate volume. However, large-volume watery stools, bloody stools, or symptoms of dysentery may occur. Rarely, NTS causes pseudoappendicitis or an illness that mimics inflammatory bowel disease. Gastroenteritis caused by NTS is usually self-limited. Diarrhea resolves within 37 days and fever within 72 h. Stool cultures remain positive for 45 weeks after infection andin rare cases of chronic carriage (<1%)for >1 year. Antibiotic treatment usually is not recommended and in some studies has prolonged fecal carriage. Neonates, the elderly, and immunosuppressed patients (e.g., transplant recipients, HIV-infected persons) with NTS gastroenteritis are especially susceptible to dehydration and dissemination and may require hospitalization and antibiotic therapy. Acute NTS gastroenteritis was associated with a threefold increased risk of dyspepsia and irritable bowel syndrome at 1 year in a recent study from Spain. EHEC Colonization of the colon and perhaps the ileum results in symptoms after an incubation period of 3 or 4 days. Colonic edema and an initial secretory diarrhea may develop into the STEC/EHEC hallmark syndrome of grossly bloody diarrhea (as detected by history or examination) in >90% of cases. Significant abdominal pain and fecal leukocytes are common (70% of cases), whereas fever is not; a lack of fever often results in diagnostic consideration of noninfectious conditions (e.g., intussusception and inflammatory or ischemic bowel disease). Occasionally, infections caused by Clostridium difficile, Campylobacter, and Salmonella present in a similar fashion. STEC/EHEC disease is usually self-limited, lasting 510 days. This infection can be complicated by HUS, which occurs 214 days after diarrhea in 28% of cases and most often affects very young or elderly patients. Intestinal Amebiasis Symptomatic amebic colitis develops 26 weeks after the ingestion of infectious cysts. A gradual onset of lower abdominal pain and mild diarrhea is followed by malaise, weight loss, and diffuse lower abdominal or back pain. Cecal involvement may mimic acute appendicitis. Patients with full-blown dysentery may pass 1012 stools per day. The stools contain little fecal material and consist mainly of blood and mucus. In contrast to those with bacterial diarrhea, fewer than 40% of patients with amebic dysentery are febrile. Virtually all patients have heme-positive stools. More fulminant intestinal infection, with severe abdominal pain, high fever, and profuse diarrhea, is rare and occurs predominantly in children. Patients may develop toxic megacolon, in which there is severe bowel dilation with intramural air.