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47
Escherichia coli Diarrhea
(Including Hemolytic Uremic Syndrome) Clinical Manifestations
At least 5 pathotypes of diarrhea-producing Escherichia coli strains have been identified.
Clinical features of disease caused by each pathotype are summarized in Table 47.1.
• Shiga toxin-producing E coli (STEC) organisms are associated with diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Shiga toxin-producing E coli O157:H7 is the serotype most often implicated in outbreaks and is consistently a virulent STEC serotype, but other sero- types can also cause illness. Shiga toxin- producing E coli illness typically begins with nonbloody diarrhea. Stools usually become bloody after 2 or 3 days, representing the onset of hemorrhagic colitis. Severe abdominal pain is typically short lived, and low-grade fever is present in approximately one-third of cases. In people with presump- tive diagnoses of intussusception, appendici- tis, inflammatory bowel disease, or ischemic colitis, disease caused by E coli O157:H7 and other STEC should be considered.
Table 47.1
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occur, diarrhea is usually watery without blood or mucus. Patients are often febrile, and stools can contain leukocytes.
• Enteroaggregative E coli (EAEC) organisms cause watery diarrhea and are common in people of all ages in industrialized as well as resource-limited countries. Enteroaggre- gative E coli has been associated with pro- longed diarrhea (≥14 days). Asymptomatic infection can be accompanied by subclinical inflammatory enteritis, which can cause growth disturbance.
• Sequelae of STEC infection: Hemolytic uremic syndrome is a serious sequela of STEC enteric infection. E coli O157:H7 is the STEC serotype most commonly associated with HUS, which is defined by the triad of microangiopathic hemolytic anemia, throm- bocytopenia, and acute renal dysfunction.
Children younger than 5 years are at highest risk of HUS, which occurs in approximately 15% of children infected with STEC. Hemo- lytic uremic syndrome typically develops 7 days (up to 2 weeks; rarely, 2–3 weeks) after onset of diarrhea. More than 50% of children with HUS require dialysis, and 3% to 5% die.
Patients with HUS can develop neurologic complications (eg, seizures, coma, cerebral vessel thrombosis). Children presenting with an elevated white blood cell count (>20 x 109/mL) or oliguria or anuria are at higher risk of poor outcome, as are, seemingly para- doxically, children with hematocrit close to normal rather than low. Most who survive have a very good prognosis, which can be predicted by normal creatinine clearance and no proteinuria or hypertension 1 or more years after HUS.
Etiology
Five pathotypes of diarrhea-producing E coli have been distinguished by pathogenic and clinical characteristics. Each pathotype com- prises characteristic serotypes, indicated by somatic (O) and flagellar (H) antigens.
Epidemiology
Transmission of most diarrhea-associated E coli strains is from food or water contami- nated with human or animal feces or from
infected symptomatic people. Shiga toxin- producing E coli is shed in feces of cattle and, to a lesser extent, sheep, deer, and other rumi- nants. Human infection is acquired via con- taminated food or water or via direct contact with an infected person, a fomite, or a carrier animal or its environment. Many food vehicles have caused E coli O157 outbreaks, including undercooked ground beef (a major source), raw leafy greens, and unpasteurized milk and juice.
Outbreak investigations have also implicated petting zoos, drinking water, and ingestion of recreational water. The infectious dose is low;
thus, person-to-person transmission is com- mon in households and has occurred in child care centers. Less is known about the epidemi- ology of STEC strains other than O157:H7.
Among children younger than 5 years, the incidence of HUS is highest in 1-year-olds and lowest in infants. A severe outbreak of bloody diarrhea and HUS occurred in Europe in 2011;
the outbreak was attributed to an EAEC strain of serotype O104:H4 that had acquired the Shiga toxin 2a-encoding phage. This experi- ence highlights the importance of considering serotypes other than O157:H7 in outbreaks and cases of HUS.
With the exception of EAEC, non-STEC pathotypes are most commonly associated with disease in resource-limited countries, where food and water supplies commonly are contaminated and facilities and supplies for hand hygiene are suboptimal. For young chil- dren in resource-limited countries, transmis- sion of ETEC, EPEC, and other diarrheal pathogens via contaminated weaning foods (sometimes by use of untreated drinking water in the foods) is also common. Enterotoxigenic E coli diarrhea occurs in people of all ages but is especially frequent and severe in infants in resource-limited countries. Enterotoxigenic E coli is a major cause of traveler’s diarrhea.
Enteroaggregative E coli is increasingly recog- nized as a cause of diarrhea in the United States.
Incubation Period
For most E coli strains, 10 hours to 6 days; for E coli O157:H7, 3 to 4 days (range, 1–8 days).
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Diagnostic Tests
Diagnosis of infection caused by diarrhea- associated E coli other than STEC is difficult because tests are not widely available to dis tinguish these pathotypes from normal E coli strains present in stool flora. Culture- independent tests are necessary to detect non- O157:H7 STEC infections. Newly licensed multiplex polymerase chain reaction assays can detect a variety of enteric infections, including ETEC and STEC. Several commercially avail- able, sensitive, specific, and rapid assays for Shiga toxins in stool or broth culture of stool, including enzyme immunoassays and immu- nochromatographic assays, have been approved by the US Food and Drug Administration. All stool specimens submitted for routine testing from patients with acute community-acquired diarrhea should be cultured simultaneously for E coli O157:H7 and tested with an assay that detects Shiga toxins. Most E coli O157:H7 iso- lates can be identified presumptively when grown on sorbitol-containing selective media.
Shiga toxin-producing E coli should also be sought in stool specimens from all patients diagnosed with postdiarrheal HUS. However, the absence of STEC does not preclude the diagnosis of probable STEC-associated HUS because HUS is typically diagnosed a week or more after onset of diarrhea, when the organ- ism may not be detectable by conventional methods. Selective enrichment followed by immunomagnetic separation can markedly increase the sensitivity of STEC detection, so this testing is especially useful for patients who were not tested early in their diarrheal illness. The test is available at some state public health laboratories and at the Centers for Disease Control and Prevention. DNA probes are also available in reference and research laboratories. Serologic diagnosis using enzyme immunoassay to detect serum antibodies to
E coli O157 and O111 lipopolysaccharides is available at the Centers for Disease Control and Prevention for outbreak investigations and for patients with HUS.
Treatment
Orally administered electrolyte-containing solutions are usually adequate to prevent or treat dehydration and electrolyte abnormali- ties. Antimotility agents should not be admin- istered to children with inflammatory or bloody diarrhea. Patients with proven or suspected STEC infection should be fully but prudently rehydrated as soon as clinically feasible. Careful monitoring of patients with hemorrhagic colitis (including complete blood cell count with smear, blood urea nitrogen, and creatinine concentrations) is recom- mended to detect changes suggestive of HUS.
If patients have no laboratory evidence of hemolysis, thrombocytopenia, or nephropathy 3 days after resolution of diarrhea, their risk of developing HUS is low. In resource-limited countries, nutritional rehabilitation should be provided as part of case management algo- rithms for diarrhea where feasible. Feeding, including breastfeeding, should be continued for young children with E coli enteric infection.
• Antimicrobial therapy: Most experts advise not prescribing antimicrobial therapy for children with E coli O157:H7 enteritis or a clinical or epidemiologic picture strongly suggestive of STEC infection. Empirical self-treatment of diarrhea for travelers to a resource-limited country is effective, and azithromycin or a fluoroquinolone has been the most reliable agent for therapy;
the choice of therapy depends on the patho- gen and local antibiotic resistance patterns.
Rifaximin may be used for people 12 years and older.
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Image 47.1
Escherichia coli in the intestine of an 8-month-old suffering from chronic diarrhea (fluorescent antibody stain). in a small number of individuals (mostly children <5 years and the elderly), E coli can cause hemolytic uremic syndrome, in which the red blood cells are destroyed and the kidneys fail. Courtesy of Centers for Disease Control and Prevention.
Image 47.2
Transmission electron micrograph of Escherichia coli O157:H7. Courtesy of Centers for Disease Control and Prevention/Peggy S. Hayes.
Image 47.3
Enterohemorrhagic Escherichia coli O157:H7. Number of reported cases in the united States and uS territories, 2003. Courtesy of Morbidity and Mortality Weekly Report.
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Image 47.4
Shiga toxin-producing Escherichia coli. Number of reported cases—united States and uS territories, 2012. Courtesy of Morbidity and Mortality Weekly Report.
Image 47.5
Hemolytic uremic syndrome, postdiarrheal. Number of reported cases—united States and uS territories, 2012. Courtesy of Morbidity and Mortality Weekly Report.