Correspondence
Escherichia coli and the Hemolytic–Uremic Syndrome
N Engl J Med 1997; 336:515-516February 13, 1997
- Article
To the Editor:
The report by Tarr et al. (Aug. 29 issue)1 and the accompanying editorial2 make clear the importance of Shiga-toxin–producing Escherichia coli belonging to serotypes other than O157:H7. However, in their editorial Drs. Rondeau and Peraldi suggest that “other means of detecting Shiga toxin . . . will be required to identify . . . other E. coli serotypes.”2 There are assays approved by the Food and Drug Administration for detecting Shiga-toxin–producing E. coli in stool samples, and these assays are already being used in the United States to detect these pathogens, including Shiga-toxin–producing O103 serotypes.
We have seen two cases of diarrheal disease associated with Shiga-toxin–producing E. coli O103. Both were found as part of surveillance projects to determine the local prevalence of Shiga-toxin–producing E. coli and were identified with a commercially available enzyme immunoassay (Meridian Diagnostics) for the detection of these organisms. The first case was in a 79-year-old man with a two-day history of bloody diarrhea. Tests for routine enteric pathogens including E. coli O157:H7 were negative, but the patient was found to have Shiga-toxin–producing E. coli O103:Hu. The second case was in a 38-year-old man with nonbloody diarrhea who also had a negative test for routine enteric pathogens but was found to have E. coli O103:H2.
Close to 100 serotypes of Shiga-toxin–producing E. coli have been associated with either hemorrhagic colitis or the hemolytic–uremic syndrome in North America. The current absence of testing for these bacteria means that the true prevalence of disease due to these pathogens is unknown. However, there have been many sporadic cases of the hemolytic–uremic syndrome and hemorrhagic colitis in the United States that were associated with Shiga-toxin–producing E. coli belonging to serotypes other than O157:H7, as well as at least one outbreak.3 Recent surveys4 suggest that only a quarter of hospitals are routinely testing for E. coli O157:H7; even fewer laboratories are examining samples for the non-O157 serotypes, including O103, which are obviously capable of causing the hemolytic–uremic syndrome.1 There is little excuse for failing to examine stool samples for these potentially deadly pathogens.
4 ReferencesDavid W.K. Acheson, M.D.
Lucas E. Wolf, M.D.
New England Medical Center, Boston, MA 02111Choong H. Park, M.D.
Fairfax Hospital, Falls Church, VA 220421
Tarr PI ,Fouser LS ,Stapleton AE , et al. Hemolytic-uremic syndrome in a six-year-old girl after a urinary tract infection with Shiga-toxin-producing Escherichia coli O103:H2. N Engl J Med 1996;335:635-638
Full Text | Web of Science | Medline2
Rondeau E ,Peraldi M-N . Escherichia coli and the hemolytic-uremic syndrome. N Engl J Med 1996;335:660-662
Full Text | Web of Science | Medline3
Outbreak of acute gastroenteritis attributable to Escherichia coli serotype O104:H21 -- Helena, Montana, 1994MMWR Morb Mortal Wkly Rep 1995;44:501-503
Medline4
Morris AJ ,Murray PR ,Reller LB . Contemporary testing for enteric pathogens: the potential for cost, time, and health care savings. J Clin Microbiol 1996;34:1776-1778
Web of Science | Medline
To the Editor:
Tarr et al. describe the isolation from a urine sample from a six-year-old girl of sorbitol-fermenting E. coli O103:H2 that produced Shiga toxin 1. The authors expressed disappointment about the lack of easy-to-perform but sensitive methods for screening for sorbitol-fermenting, Shiga-toxin–producing E. coli. My colleagues and I found an enzyme immunoassay (Premier EHEC, Meridian Diagnostics) that offers a straightforward, rapid, and cost-effective way of screening for such pathogens.1,2 Assays of stool samples, MacConkey-broth cultures incubated overnight, and colonies from agar plates usually provide results within three hours, with a sensitivity of 94.1 percent and a specificity of 99.4 percent, according to the manufacturer. The enzyme immunoassay fails to detect Shiga toxin 2e, which is produced by E. coli O101 strains.2 Positive results require confirmation by methods that are usually not available, such as the DNA-based cytotoxicity assay, colony hybridization, and polymerase chain reaction, as mentioned by Tarr et al. and others.3,4 Using this enzyme immunoassay, we have been able to detect two serogroups — O146:H- and O113:H53 — that were formerly not described as Shiga-toxin–producing strains.2
One of our samples, which finally revealed sorbitol-positive E. coli O113:H53, had no reaction after the recommended incubation period, but there was a strong positive reaction after overnight incubation at room temperature. The results were interpreted visually and spectrophotometrically. This sample would have been reported as negative if it had been treated strictly according to the operating manual.
For patients with the hemolytic–uremic syndrome or bloody diarrhea without microbiologic findings, this enzyme immunoassay appears to be an appropriate screening test. Positive results should be confirmed by a well-equipped reference laboratory.
4 ReferencesDieter W. Rossboth, M.D.
Stafflerstrasse, 9, A-6020 Innsbruck, Austria1
Perera LP ,Marques LR ,O'Brien AD . Isolation and characterization of monoclonal antibodies to Shiga-like toxin II of enterohemorrhagic Escherichia coli and use of the monoclonal antibodies in a colony enzyme-linked immunosorbent assay. J Clin Microbiol 1988;26:2127-2131
Web of Science | Medline2
Allerberger F ,Rossboth D ,Dierich MP ,Aleksic S ,Schmidt H ,Karch H . Prevalence and clinical manifestations of Shiga toxin-producing Escherichia coli infections in Austrian children. Eur J Clin Microbiol Infect Dis 1996;15:545-550
CrossRef | Web of Science | Medline3
Newland JW ,Neill RJ . DNA probes for Shiga-like toxins I and II and for toxin-converting bacteriophages. J Clin Microbiol 1988;26:1292-1297
Web of Science | Medline4
Bockemuhl J ,Aleksic S ,Karch H . Serological and biochemical properties of Shiga-like toxin (verocytotoxin)-producing strains of Escherichia coli, other than O-group 157, from patients in Germany. Zentralbl Bakteriol 1992;276:189-195
Medline
Author/Editor Response
The authors reply:
To the Editor: We thank Acheson et al. and Rossboth for their reports of patients infected with Shiga-toxin–producing E. coli belonging to serotypes other than O157:H7. As in the case we described, such pathogens in stool cultures would be overlooked by screening techniques that are directed at identifying non–sorbitol-fermenting E. coli O157:H7, but not other Shiga-toxin–producing organisms, which usually ferment sorbitol only after overnight incubation.
We agree with Acheson et al. that all physicians and diagnostic laboratories should have access to a means of detecting Shiga-toxin–producing E. coli belonging to serotypes other than O157:H7.1 Ideally, attempts to detect such organisms would be incorporated into the evaluation of all stool samples submitted for microbiologic analysis. However, the decision to screen all stool samples for these organisms, rather than stool samples from a subgroup of patients, will probably depend on the cost, ease of performance, and yield of these tests. It is disturbing that screening for E. coli O157:H7, an easy, inexpensive process that has considerable clinical and public health value, is not universally performed by U.S. microbiologists.2
We urgently need prospective studies, preferably with controls, to determine the frequency with which Shiga-toxin–producing E. coli of serotypes other than O157:H7 are present in stool samples submitted for microbiologic study. We also need to isolate and study these toxin-producing strains to identify the non–toxin-associated virulence traits that render certain strains pathogenic for humans. On the basis of these data, we will be better able to design strategies of detection, treatment, and infection prevention.
2 ReferencesPhillip I. Tarr, M.D.
Ann E. Stapleton, M.D.
University of Washington School of Medicine, Seattle, WA 98195Richard A. Wilson, Ph.D.
Pennsylvania State University, University Park, PA 168021
Tarr PI ,Neill MA . The problem of non-O157:H7 Shiga toxin (verocytotoxin)-producing Escherichia coli. J Infect Dis 1996;174:1136-1139
CrossRef | Web of Science | Medline2
Boyce TG ,Pemberton AG ,Wells JG ,Griffin PM . Screening for Escherichia coli O157:H7 -- a nationwide survey of clinical laboratories. J Clin Microbiol 1995;33:3275-3277
Web of Science | Medline
Author/Editor Response
We agree with Acheson et al. that enzyme immunoassays for detecting Shiga-toxin–producing E. coli in stool samples are available, but as pointed out by Dr. Rossboth, they do not detect all the Shiga-toxin isoforms, and false positive results have been observed.1 These tests appear to be useful and less time consuming than DNA-based methods to identify both Shiga-toxin–producing E. coli O157 and other serotypes that produce Shiga toxin, but their place in the diagnostic workup of patients with diarrhea and the hemolytic–uremic syndrome remains to be determined.
1 ReferencesEric Rondeau, M.D., Ph.D.
Marie-Noëlle Peraldi, M.D.
Hôpital Tenon, 75020 Paris, France1
Allerberger F ,Rossboth D ,Dierich MP ,Aleksic S ,Schmidt H ,Karch H . Prevalence and clinical manifestations of Shiga toxin-producing Escherichia coli infections in Austrian children. Eur J Clin Microbiol Infect Dis 1996;15:545-560
CrossRef | Web of Science | Medline
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KERSTIN LUDWIG, ENKE GRABHORN, MARTIN BITZAN, CHRISTOPH BOBROWSKI, MARKUS J. KEMPER, INGO SOBOTTKA, RAINER LAUFS, HELGE KARCH, AND, DIRK E. M??LLER-WIEFEL. (2002) Saliva IgM and IgA Are a Sensitive Indicator of the Humoral Immune Response to Escherichia coli O157 Lipopolysaccharide in Children with Enteropathic Hemolytic Uremic Syndrome. Pediatric Research 52:2, 307-313
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Rita Prager, Almut Liesegang, W. Voigt, W. Rabsch, Angelika Fruth, H. Tschäpe. (2002) Clonal diversity of Shiga toxin-producing Escherichia coli O103:H2/H− in Germany. Infection, Genetics and Evolution 1:4, 265-275
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O. Franklin, M. Burch. (2000) Applied physiology: understanding cardiac failure. Current Paediatrics 10:4, 284-288
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