Escherichia coli 0157 : H 7 Infection in Humans

Escherichia coli serotype O157:H7 was first isolated in 1982, when 47 persons in Michigan and Oregon developed bloody diarrhea after eating hamburgers contaminated with the organism [1]. Retrospective examination of more than 3000 E. coli cultures obtained between 1973 and 1982 has found only one isolation with serotype O157:H7; it was from a 50-year-old woman who had had an episode of acute, self-limited, grossly bloody diarrhea in 1975 [1]. Since the initial reports, sporadic cases [2-9] and outbreaks [10-24] of E. coli O157:H7 infection have increasingly been reported, and surveillance and prospective studies to identify and characterize diseases associated with E. coli O157:H7 have been started in Canada, the United Kingdom, and the United States [3-925, 26]. The first major step toward defining the pathogenic potential of E. coli O157:H7 was made in 1983, when isolates of this serotype were found to produce a toxin [27]. This toxin has been called both Shiga-like toxin, because of its close relation to Shiga toxin, and Vero-toxin, because of its toxicity to Vero (green monkey kidney) cells in tissue culture. Subsequent studies [28-34] have shown that E. coli O157:H7 produces at least two distinct Shiga-like toxins and that O157:H7 is only one serotype of Shiga-like toxin-producing E. coli. To distinguish their clinical and pathologic features from those of enterotoxigenic, enteroinvasive, and enteropathogenic E. coli, these Shiga-like toxin-producing strains of E. coli, which cause hemorrhagic colitis, have also been called enterohemorrhagic E. coli [35]. Serotypes other than O157:H7 can cause illness similar to that caused by E. coli O157:H7, because many strains of E. coli can produce Shiga-like toxin. Moreover, many serotypes of Shiga-like toxin-producing E. coli other than O157:H7 have been isolated from patients with hemorrhagic colitis or the hemolytic- uremic syndrome. Although few studies have been done to determine the incidence of diarrheal illness caused by Shiga-like toxin-producing E. coli other than O157:H7, none of these organisms is a common cause of diarrhea. Thus, a 2-year survey in Canada reported that 0.7% of stools (36 of 5415) showed Shiga-like toxin-producing E. coli other than O157:H7; this rate was higher than that for shigellae, and the serotypes most often isolated were O26:H11 and O103:H2 [6]. Serotype O157:H7 was also identified in 7 of these 36 stools, bringing into question the precise role of the non-O157:H7 serotype in causing the diarrhea. Shiga-like toxin-producing E. coli other than O157:H7, such as O2:H5, have also been isolated from patients with ulcerative colitis, but, again, their precise role in causing this disease or its exacerbations is unclear [36]. What is clear is that many more studies are needed to define the roles of Shiga-like toxin-producing coliforms other than O157:H7 in causing human disease. Many species of E. coli produce Shiga-like toxin, but we focus on E. coli O157:H7 because it is the most common. The term Shiga-like toxin is preferred to Verotoxin because it emphasizes the common mechanism of action of the toxins produced by certain species of E. coli and the Shiga toxin elaborated by shigellae, as well as the wide target cell of injury, that is, cells with the surface receptor globotriaosyl ceramide. Methods Articles on E. coli O157:H7 were identified through MEDLINE and through review of bibliographies of relevant articles. All articles and case reports describing E. coli O157:H7 and its infection were selected. Data were abstracted without judgments about study design. Data quality and validity were assessed by independent author reviews. Clinical Manifestations Infection with E. coli O157:H7 presents with a wide spectrum of clinical manifestations, including severe abdominal cramps with little or no fever and watery diarrhea that often progresses to grossly bloody diarrhea [37]. Infection can be asymptomatic [13, 15, 19] or can present with only nonbloody diarrhea [4, 5, 8, 10, 11, 13, 16, 20, 26]. Extraintestinal involvement, including cardiac and neurologic manifestations, has been reported [38], and infection can be associated with the hemolytic-uremic syndrome [14, 16, 18, 19, 24] and thrombotic thrombocytopenic purpura [16, 39-41]. The disease can be fatal [15, 16, 18, 19, 37]. Asymptomatic Infection and Nonbloody Diarrhea Cases of asymptomatic E. coli O157:H7 infection have occasionally been detected in outbreaks [13, 15, 19], but the incidence rates are difficult to estimate because stool samples from asymptomatic persons are rarely obtained for culturing. In an outbreak in Canada that involved kindergarten children, 31% of those exposed to the implicated source (19 of 62) were asymptomatic [17]. Fifty-three percent of the asymptomatic children (10 of 19) had laboratory evidence of E. coli O157:H7. Nonbloody diarrhea without progression to hemorrhagic colitis has also been reported [4, 5, 8, 10, 11, 13, 16, 20, 26]. It was noted in 18% of culture-confirmed cases (3 of 17) in a nursing home outbreak of E. coli O157:H7 infection [13] and in as many as two of four children with culture-positive stools in a day care center [20]. Although cases of nonbloody diarrhea occur in outbreaks, the routine screening of all stool specimens for E. coli O157:H7 during one outbreak period showed that the number of these cases is probably small [16]. Patients with nonbloody diarrhea have less severe disease, are less likely to develop the hemolytic-uremic syndrome, and are less likely to die than are patients with bloody stools [11]. However, nonbloody diarrhea progressing to the hemolytic-uremic syndrome has been reported. In one 2-year prospective study, two of nine confirmed cases of E. coli O157:H7-associated hemolytic-uremic syndrome were preceded by nonbloody diarrhea [26]. Patients with bloody stools have a longer duration of diarrhea and report abdominal cramps and vomiting more often than do those with nonbloody diarrhea [20]. Hemorrhagic Colitis Hemorrhagic colitis caused by E. coli O157:H7 is a clinical syndrome that consists of abdominal cramps; diarrhea that progresses to become bloody; radiologic or endoscopic evidence of colonic mucosal edema, erosion, or hemorrhage; and the absence of conventional enteric organisms in the stool [42]. This syndrome was first reported in 1971 [43], when five young adults developed reversible segmental colitis that rapidly resolved within 2 weeks without specific therapy. The term evanescent colitis was used to describe this entity as a clinical syndrome distinct from ulcerative, granulomatous, and ischemic colitis [43]. After the outbreaks of hemorrhagic colitis in Michigan and Oregon [1] and subsequent similar outbreaks, E. coli O157:H7 came to be recognized as an important etiologic agent for hemorrhagic colitis. Hemorrhagic colitis may be the only manifestation of E. coli O157:H7 infection, or it may herald the development of the hemolytic-uremic syndrome. Thirty-eight percent to 61% of such infections result in hemorrhagic colitis [44], and surveillance studies [8, 9] have found E. coli O157:H7 in 27% to 36% of sporadic cases of hemorrhagic colitis. Infection with E. coli O157:H7 usually begins with the sudden onset of severe abdominal cramps, which are followed within hours by watery diarrhea that progresses to grossly bloody stools [37]. Upper gastrointestinal symptoms, such as nausea and vomiting, occur early and may be prominent. The incubation period ranges from 1 to 9 days (mean, 3.1 to 3.9 days) during community outbreaks [1, 14, 16] and from 1 to 14 days (mean, 4 to 8 days) in institutional settings [11, 13, 17, 19]. Medical attention is usually sought 2 to 3 days after the onset of diarrhea or abdominal pain, primarily because of bloody diarrhea [5], which is the most common symptom of E. coli O157:H7 infection [37]. The median duration of diarrhea is 3.0 to 7.5 days (range, 1 to more than 31 days) [10, 11, 37], and patients report a median of 10 to 11 bowel movements (range, 3 to more than 30 bowel movements) on the worst day of diarrhea [19, 37]. Diarrhea lasts longer in children (mean, 9.1 2.0 days) than in adults (mean, 6.6 1.1 days) [5], and it lasts longer in persons with bloody stools (mean, 12.2 days) than in those with nonbloody stools (mean, 6.8 days) [20]. Bloody stools develop a median of 0 to 1 days (range, 0 to 8 days) after the onset of diarrhea [11, 37] and last a median of 2 to 5 days (range, 1 to 22 days) [5, 10, 11, 37]. The amount of blood in each stool ranges from streaks to more than 4 cups on the worst day (median, 4.5 tablespoons) [37]. Most of the infected children (91%) in an outbreak in a day care center produced less than 1 tablespoon of blood per stool [20], whereas patients in other outbreaks have reported that bowel movements were essentially all blood with little fecal material [1, 5]. Other symptoms related to E. coli O157:H7 infection include severe abdominal cramps, right lower quadrant pain, nausea, vomiting, fever, and chills [1, 4, 10, 26]. The incidence of fever ranges from 0% to 32% [1, 5, 10, 11, 16, 19, 20] and was as high as 64% among persons with bloody diarrhea in one day care center outbreak [20]. When present, fever is usually mild, unlike that seen with the bloody diarrhea of shigellosis, amebiasis, campylobacteriosis, or enteroinvasive E. coli infection [1]. Abdominal distention and tenderness may be present, but the results of physical examination are usually normal [8, 19]. Laboratory studies usually show leukocytosis with moderate left shift and a mean leukocyte count of 13.0 to 14.0 109/L (range, 6.2 to 20.0 109/L) [1, 15, 19]. Hematocrit is generally not significantly decreased despite the bloody nature of the stools. The results of other studies, including erythrocyte sedimentation rate, serum electrolyte concentrations, liver test results, prothrombin times, and urinalysis results, are typically normal [1]. Mucus and leukocytes may be