E. coli, Europe, and Hemolytic Uremic Syndrome

Abstract & Commentary

By Megan M. Chock and Philip R. Fischer MD, DTM&H

Ms. Chock is a medical student at the Mayo Medical School, Rochester, MN, and Dr. Fischer is Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Ms. Chock and Dr. Fischer report no financial relationships to this field of study.

Synopsis: In recent months, Escherichia coli O104:H4 has infected more than 4,000 people and caused 880 cases of hemolytic uremic syndrome (HUS) in Europe, with the majority of cases reported in Germany and with more recent outbreaks in France and Switzerland. Travelers should implement food hygiene precautions to prevent infection when visiting Europe.

Sources: Frank C, et al; the HUS Investigation Team. Epidemic profile of shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany — Preliminary Report. N Engl J Med 2011 June 22; Epub ahead of print;

World Health Organization, Regional Office for Europe. Outbreaks of E. coli O104:H4 infection: Update 28, 01-07-2011. Available at: www.euro.who.int/en/what-we-do/health-topics/emergencies. Accessed July 7, 2011;

Centers for Disease Control and Prevention. EHEC outbreak Update 27, 30 June 2011. Investigation Update: Outbreak of Shiga toxin-producing E. coli O104 (STEC O104:H4) Infections Associated with Travel to Germany. Available at: www.cdc.gov/ecoli/2011/ecoliO104/. Accessed July 7, 2011.

As of june 29, 2011, german authorities reported 3,189 cases of entero-hemorrhagic E. coli (EHEC) infections, and 884 other cases have also been identified. Since May 2, 2011, Germany has reported 841 cases of hemolytic uremic syndrome (HUS) caused by the EHEC strain E. coli O104:H4. Most of the infections have been reported in northern Germany or in people who have traveled to this area. Cases of HUS and EHEC have been reported throughout 13 other European countries and the Centers for Disease Control and Prevention (CDC) has reported five confirmed and one probable case of E. coli O104:H4 infection in the United States. Of the six U.S. cases, five recently traveled to Germany. The cause of the outbreak has been traced to fresh sprouts produced by a farm in Lower Saxony, northern Germany. Current recommendations are to avoid eating raw sprouts regardless of their origin.

On June 24, 2011, France reported a new outbreak of E. coli and HUS in which E. coli O104:H4 was confirmed in four of the eight cases, and on June 28, 2011, Sweden reported an isolated case of O104:H4 infection. None of these patients had traveled to Germany, and first investigations indicate that locally grown sprouts may be the associated cause.


The outbreak of hemolytic uremic syndrome caused by Shiga toxin-producing E. coli (STEC) has been ongoing in Germany since May 2011 and peaked on May 21, 2011. Hemolytic uremic syndrome is a dangerous complication that can arise from STEC infection. HUS frequently includes acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia; the central nervous system is less frequently involved. Features of HUS usually begin 5-10 days after the onset of diarrhea. Most often, HUS is caused by infection with E. coli O157:H7; however, the STEC strain responsible for Germany's current outbreak is E. coli O104:H4.

The outbreak caused by E. coli O104:H4 is different than other outbreaks of STEC infection in several ways. First, HUS has complicated a higher proportion of infections with E. coli O104:H4 than other strains. Usually, HUS complicates 6%-9% of STEC infections in adults and 15% of STEC infections in children; however, HUS has been a complication in 25% of the E. coli O104:H4 infections. Second, while other STEC strains like E. coliO157:H7 tend to affect children more than adults, approximately 89% of HUS associated with the E. coli O104:H4 strain occurred in adults, and more than 65% of these cases were in females. Although the exact reasons for these age and gender risks are not known, the increased adult incidence of HUS in the current outbreak may be due to varied modes of transmission. E. coli O157:H7 maintains a wild reservoir in cattle, and humans are infected by ingesting fecal material or through direct human contact; perhaps children eat fewer bean sprouts and, thus, are at less risk of O104:H4 infection. In the active Europe outbreak, it appears that the O104:H4 may have stemmed from a genetic mutation of enteroaggregative E .coli, which normally causes watery diarrhea and does not have a zoonotic reservoir. The O104:H4 STEC strain contains genes from both enteroaggregative and Shiga-toxin Type 2 E. coli, which may be responsible for its altered virulence.

According to the Robert Koch Institute, which began investigating an outbreak of HUS in northern Germany on May 20, 2011, the outbreak began to grow on May 8 before peaking around May 21, 2011. The source of infection was attributed to cucumbers, tomatoes, and leafy vegetables before epidemiological studies indicated that raw sprouts from a farm in Lower Saxony were responsible for the current outbreak.

A person with symptoms of STEC or HUS who has recently traveled to Germany or has been in close contact with an ill person should get medical attention. STEC infection usually manifests itself clinically as acute bloody diarrhea and hemorrhagic colitis. Infected persons can then develop HUS, which sometimes leads to permanent renal and neurological problems. The diagnosis is usually made with Shiga toxin detection. In the O104:H4 outbreak, bloody diarrhea with abdominal cramps was the most common clinical sign in adults, and the median incubation period was 8 days. Treatment of hemolytic uremic syndrome is supportive; red cell and platelet transfusions are sometimes needed, and dialysis may be used for renal failure. Inhibition of complement complex formation holds promise of helping patients with severe HUS.1

Travelers should follow food safety precautions when visiting Europe to prevent infection. The CDC and German authorities' current recommendation to prevent further spread of E. coli O104:H4 is to avoid consumption of any raw bean or seed sprouts. People should only consume sprouts that have been cooked at a temperature of at least 70° C, which kills the E. coli bacteria.2 The WHO also advises people to thoroughly wash their hands after touching seeds for planting or sprouting.2 In addition, people should exercise general hygiene principles and wash their hands before and after handling or eating food items and after using the bathroom.

The current outbreak of E. coli O104:H4 infections should remind travelers that there are risks to seemingly safe European travel. In addition, measles infection is an active public health concern in Europe, with more than 7,000 cases reported in France alone from January to March 2011 and more than 11,000 cases in 38 other countries in Europe.3 More than 75% of these cases occurred in people who had not been vaccinated. All travelers should be up to date on all of their vaccinations, even including full measles protection for European travel.4 A recent publication details risks specific to travel in various parts of the world, even North America.5


  1. Lapeyraque AL, et al. Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med 2011;364:2561-2563.
  2. World Health Organization, Regional Office for Europe. Outbreaks of E. coli O104:H4 infection: WHO/Europe gives public health advice. Available at: www.euro.who.int/en/what-we-do/health-topics/emergencies. Accessed July 5, 2011.
  3. World Health Organization, Regional Office for Europe. WHO Epidemiological Brief June 2011. Available at: www.euro.who.int/__data/assets. Accessed July 4, 2011.
  4. Centers for Disease Control and Prevention. 2011 Measles Update. Available at: wwwnc.cdc.gov/travel/notices/in-the-news/measles.htm. Accessed July 5, 2011.
  5. Petersen E, et al, eds. Infectious Diseases: A Geographic Guide. Oxford, UK: Wiley-Blackwell; 2011.