One-Two Punch May Explain Power of E. Coli Outbreak
By Michael Smith, North American Correspondent, MedPage Today Published: June 22, 2011 Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
A combination of bacterial traits may explain the unusual virulence of the deadly food-borne Escherichia coli outbreak in Germany, two groups of researchers reported.
The E. coli O104:H4 strain found in the outbreak involves clones of a type – dubbed HUSEC041 – that was first isolated in 2001 from a patient with hemolytic uremic syndrome (HUS), according to Helge Karch, PhD, of the University of Münster in Münster, Germany, and colleagues.
The clones combine the ability to produce so-called Shiga toxins with the ability to clump together and stick to the cells lining the gut wall, Karch and colleagues reported online in The Lancet Infectious Diseases.
They also have acquired an ability to resist beta-lactam antibiotics that was absent in the 2001 isolate, Karch and colleagues reported.
Another German research team, led by Dirk Werber, DVM, of the Robert Koch Institute in Berlin, noted similar findings in a preliminary report online in the New England Journal of Medicine.
Starting in early May, Karch and colleagues noted, an outbreak of HUS and bloody diarrhea caused by E. coli O104:H4 hit Germany. As of June 20, there have been 810 cases of HUS, 2,684 non-HUS cases, and 39 deaths.
Almost 100 infections with 39 cases of HUS have been reported elsewhere in Europe and North America, they said, mainly among travellers returning from Germany.
The outbreak "tragically shows that blended virulence profiles in enteric pathogens, introduced into susceptible populations, can have extreme consequences for infected people," Karch and colleagues argued.
The usual toll in Germany in a year is about 1,000 symptomatic Shiga-toxin-producing E. coli infections and 60 cases of hemolytic uremic syndrome, according to Hugh Pennington, MBBS, PhD, an emeritus professor at the University of Aberdeen in Aberdeen, Scotland.
In an accompanying commentary, Pennington wrote that it's reasonable to think that the blending of virulence traits was responsible for the higher than usual toll.
He added that the pattern of disease – mainly in young adults and predominately women – is probably a function of the E. coli vector, which was probably bean sprouts added to meals.
Karch and colleagues analyzed 80 isolates from patients that had been sent to Germany's National Consulting Laboratory for Haemolytic Uraemic Syndrome in Münster between May 23 and June 2.
All isolates were clones of the HUSEC041 type, they found, and all had the stx gene that is characteristic of enterohemorrhagic strains – those that produce Shiga toxins.
They also showed the so-called "stacked-brick" adherence pattern, characteristic of enteroaggregative strains of the bacteria, Karch and colleagues reported.
Also, they added, analysis showed they had an extended-spectrum beta-lactamase antibiotic resistance profile that made them resistant to all penicillins and cephalosporins but left them susceptible to carbapenems.
Exactly why the outbreak strain was so virulent remains an open question, but "our data suggests some possibilities," Karch and colleagues wrote.
"The enhanced adherence of this strain to intestinal epithelial cells might facilitate systemic absorption of Shiga toxin and could explain the high frequency of progression to HUS," they argued.
Antibiotic resistance, they added, might also be involved, especially if beta-lactam drugs, used to treat infection, suppressed competing bacteria, rather than the E. coli.
In their report in the New England Journal of Medicine, Werber and colleagues tracked the course of the outbreak, noting that it was centered in northern Germany and peaked around May 21 to 23.
Most patients who developed HUS were adults -- 89%, with a median age of 43 – and 68% of them were women, they reported.
Werber and colleagues estimated the median incubation period of the bacteria to be eight days, with a median of five days from the onset of gastroenteritis to the development of HUS.
At Hamburg University Medical Center, 59 patients infected with the outbreak strain were prospectively followed, they reported, and HUS developed in 12 (or 20%), with no significant differences with respect to sex or initial symptoms and signs.
The Lancet Infectious Diseases article was supported by the German Federal Ministry of Education and Research Network Zoonoses and the University of Mu¨nster. The authors said they had no conflicts.
Pennington said he had no conflicts.
The New England Journal of Medicine authors said they had no conflicts.
Primary source: The Lancet Infectious Diseases Source reference: Bielaszewska M, et al "Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study" Lancet Infect Dis 2011; DOI:10.1016/S1473-3099(11)70165-7.
Additional source: The Lancet Infectious Diseases Source reference: Pennington H "Escherichia coli O104, Germany 2011" Lancet Infect Dis 2011; DOI:10.1016/S1473-3099(11)70166-9.
Additional source: New England Journal of Medicine Source reference: Frank, C et al "Epidemic profile of Shiga-toxin–producing escherichia coli O104:H4 outbreak in Germany -- Preliminary report" N Eng J Med 2011; DOI:10.1056/nejmoa1106483.
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