Epidemic Profile of Shiga-Toxin–Producing Escherichia coli O104:H4 Outbreak in Germany — Preliminary Report — NEJM

Epidemic Profile of Shiga-Toxin–Producing Escherichia coli O104:H4 Outbreak in Germany — Preliminary Report — NEJM: "Original Article
Epidemic Profile of Shiga-Toxin–Producing Escherichia coli O104:H4 Outbreak in Germany — Preliminary Report

Christina Frank, Ph.D., Dirk Werber, D.V.M., Jakob P. Cramer, M.D., Mona Askar, M.D., Mirko Faber, M.D., Matthias an der Heiden, Ph.D., Helen Bernard, M.D., Angelika Fruth, Ph.D., Rita Prager, Ph.D., Anke Spode, M.D., Maria Wadl, D.V.M., Alexander Zoufaly, M.D., Sabine Jordan, M.D., Klaus Stark, M.D., Ph.D., and Gérard Krause, M.D., Ph.D. for the HUS Investigation Team

June 22, 2011 (10.1056/NEJMoa1106483)

Comments open through June 28, 2011

Abstract
Article
References

Background

In this report, we provide a preliminary description of an ongoing large outbreak of gastroenteritis and the hemolytic–uremic syndrome caused by Shiga-toxin–producing Escherichia coli in Germany in May and June 2011.


Methods

We analyzed data from reports in Germany of Shiga-toxin–producing E. coli gastroenteritis and the hemolytic–uremic syndrome and clinical information on patients presenting to Hamburg University Medical Center. An outbreak case was defined as a reported case of the hemolytic–uremic syndrome or of gastroenteritis in a patient infected by Shiga-toxin–producing E. coli, serogroup O104 or serogroup unknown, with an onset of disease on or after May 1, 2011, in Germany.


Results

As of June 18, 2011, a total of 3222 outbreak cases (including 39 deaths) have been reported in Germany, 810 of which (25%) involved the hemolytic–uremic syndrome. The outbreak is centered in northern Germany and peaked around May 21 to 23. Most of the patients in whom the hemolytic–uremic syndrome has developed are adults (89%; median age, 43 years), and women are overrepresented (68%). The estimated median incubation period is 8 days, with a median of 5 days from the onset of diarrhea to the development of the hemolytic–uremic syndrome. Among 59 patients infected with the outbreak strain who were prospectively followed at Hamburg University Medical Center, the hemolytic–uremic syndrome developed in 12 (20%), with no significant difference between patients in whom the syndrome developed and those in whom it did not with respect to sex or reported initial symptoms and signs. The outbreak strain was typed as an enteroaggregative Shiga-toxin–producing E. coli O104:H4, producing extended-spectrum beta-lactamase.


Conclusions

In this large outbreak of the hemolytic–uremic syndrome, caused by an unusual strain of Shiga-toxin–producing E. coli, cases have occurred predominantly in adults, with a preponderance of cases occurring in women. The hemolytic–uremic syndrome has developed in a quarter of the symptomatic outbreak cases that have been ascertained thus far.

Figure 1Epidemiologic Curve of the Outbreak.
Figure 2Incidence of the Hemolytic–Uremic Syndrome According to County in Germany.

On May 19, 2011, the Robert Koch Institute, Germany's national-level public health authority, was informed about a cluster of three cases of the hemolytic–uremic syndrome in children admitted on the same day to the university hospital in the city of Hamburg. On May 20, a team from the Robert Koch Institute arrived in Hamburg to assist with the public health investigation. It quickly became clear that the case numbers were continuing to rise, that there were also cases in adults, and that other areas of Germany, especially northern Germany, were also affected. An investigation of the outbreak involving all levels of public-health and food-safety authorities was initiated to identify the causative agent and the vehicle of infection in order to prevent further cases of disease.

The hemolytic–uremic syndrome, which was first described in children in the 1950s,1 is characterized by the triad of acute renal failure, hemolytic anemia, and thrombocytopenia. Diarrhea-associated hemolytic–uremic syndrome occurs primarily in children, and a precipitating infection with Shiga-toxin–producing Escherichia coli, mainly of serotype O157:H7, is the primary cause.2 The usual reservoir for these bacteria is ruminants, particularly cattle. Human infection with Shiga-toxin–producing E. coli occurs through the inadvertent ingestion of fecal matter — for example, through contaminated food or water or through contact with animals or their farm environment or, secondarily, through contact with infected humans. In contrast, the hemolytic–uremic syndrome with prodromal diarrhea, indicating an infectious cause, is a rare event in adults. For example, from 1989 through 2006, only 21 of the 322 adults (7%) listed in the Oklahoma registry as having thrombotic thrombocytopenic purpura or the hemolytic–uremic syndrome presented with bloody diarrhea.3

This report provides descriptive epidemiologic, clinical, and microbiologic information on this unusual outbreak. It will be updated after the outbreak has finally ceased, in order to provide a complete picture.

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