The past few days have seen the simultaneous publication of the first vetted medical-journal pieces on the vast European outbreak of E. coli O104. They’re fascinating for what they report that is new about this perplexing epidemic — now up to 3,802 cases including 43 deaths, according to the World Health Organization — and also for the further questions they raise.

Possibly most headline-worthy: Two reports in Eurosurveillance, Europe’s peer-reviewed open-access epidemiology journal, that suggest this strain is communicable from person to person and also produces unusual and troubling symptoms.

The person-to-person case first: A team from Leiden University Medical Centre in the Netherlands describe the experience of  seven members of a Dutch family who were visiting Germany in the first weeks of the epidemic and then returned home about May 15. The young mother in the family came to the hospital May 24 after having abdominal pain and bloody diarrhea for two days. They thought she had common gastroenteritis — a bacterial or viral infection of the gut, which usually resolves on its own in a few days — and so did not give her antibiotics. Nevertheless, four days later, she developed severe hemolytic uremic syndrome, the dangerous after-effect of infection with E. coli strains that produce toxins, which destroy red blood cells, clogging the kidneys and bringing on kidney failure. HUS is often brought on by misapplied antibiotic treatment in toxin-producing (STEC) E. coli cases, but, in this case, the woman had not received any.

Once the HUS was diagnosed, the rest of the family was checked as well. The woman’s 10-month-old child, the youngest of the family group, had mild diarrhea, and so the hospital took a stool sample for culture. The next day, as the incubated culture was exhibiting growth of E. coli O104, the toddler started running a fever. The day after that, seizures began, and the toddler was admitted to intensive care and put on dialysis. The report says soberly: “The patient received prolonged mechanical ventilation and inotropic therapy. Three weeks after transfer, the patient is still on dialysis and the neurological outcome is unsure.” (Another family member, an adult, also developed diarrhea, but was never cultured for the presence of O104.)

How can the investigators be sure the toxic E. coli passed from mother to child? The main clue lies in the toddler’s age: at 10 months, too young to be eating the raw sprouts that are the implicated food. A secondary clue is the length of time between the family’s return from Germany and the onset of the toddler’s illness: 15 days, long enough that the baby’s exposure to E. coli must have happened after the family came home (Side note: If you want to know more about HUS, you can’t do better than Tara Smith’s four posts this week at Aetiology, starting here.)

Second important finding, from another paper in the same issue of Eurosurveillancedescribing a case in Munster: This O104 strain can cause severe illness even when it does not trigger HUS. A team from the Raphaelsklinik there write that a woman in her 80s came to the ER with abdominal pain, nausea, and diarrhea, but not the bloody kind. They checked her with an endoscopy and discovered that parts of her large intestine were inflamed and gangrenous. She had emergency surgery in which the left side of her colon was removed. In the ICU, she became very sick, with muscle spasms and inability to speak. She never developed HUS. The paper does not say how she ended up.

A companion editorial underlines that such serious symptoms have not been rare:

During a telephone conference on 9 June… German colleagues shared their first clinical experiences from their patients… On admission, about 80% of the patients suffered from bloody diarrhoea and 20% from watery diarrhoea. In 25% of the cases with bloody diarrhoea, signs of HUS (based on laboratory parameters of haemolysis, thrombocytopenia, and renal function tests) evolved after 3–5 days. Completely unexpected, however, was the observation that severe neurological symptoms developed after about 3–10 days in roughly 50% of patients with HUS, even though clinical and laboratory markers of HUS were improving. These patients who had at first seemed to improve or respond to therapy, deteriorated again. Some patients even had to be re-hospitalised 3–4 days after they had been discharged. Neurologists were very concerned about the severity of neurological symptoms, ranging from mild disorientation and cognitive dissociation to stupor or severe, life-threatening seizures.

Meanwhile, in Lancet Infectious Diseases, Helge Karch and colleagues of the University of Munster report their analysis of samples of O104 from 80 patients who fell ill in Germany in late May. They confirm, as had been hypothesized a few weeks ago, that the organism has what they call a “blended virulence profile,” possessing both genes from a Shiga toxin-producing  E. coli (STEC), and also genes from what is known as “enteroaggregative”  E. coli that has superior ability to attach to the gut wall — in other words, a a worst-of-both-worlds scenario combining both the ability to pump out toxins and a facility for hanging around in order to pump out a larger dose.

Intriguingly, they raise the issue of this O104 strain’s extraordinary antibiotic resistance, which has been dismissed by many commenters as not clinically relevant because standard practice for STECs is to not treat them with antibiotics. They suggest that antibiotic resistance may have played a role here if physicians treating O104 patients did not realize what they were looking at, and administered antibiotics regardless — because the antibiotics may have killed competing organisms in the gut, allowing the virulent O104 a clear field in which to reproduce.

Finally, the New England Journal of Medicine weighs in with a comprehensive assessment of the epidemic from the Robert Koch Institute in Berlin, which covers the clinical and microbiological evidence from the first weeks of the outbreak, but also lists the important questions that still remain open: Why such a high rate of HUS, in at least one in four patients? Why are the symptoms different in adults (bloody diarrhea) and children (vomiting)? Why are women over-represented in the victims compared to past STEC outbreaks? And, still unanswered — and maybe forever unanswerable — were  there unreported mild cases, and if so, was this already enormous outbreak even larger than we think?

UPDATE: Daniel Cohen at Food Safety News has a great interview with the CDC’s chief of foodborne diseases, filling in yet more rich background on this complex outbreak.

See Also:

Cites:

• Kuijper EJ et al.. Household transmission of haemolytic uraemic syndrome associated with Escherichia coli O104:H4 in the Netherlands, May 2011. Euro Surveill. 2011;16(25):pii=19897.
• Cordesmeyer S et al.. Colonic ischaemia as a severe Shiga toxin/verotoxin producing Escherichia coli O104:H4 complication in a patient without haemolytic uraemic syndrome, Germany, June 2011. Euro Surveill. 2011;16(25):pii=19895
• Jansen A, Kielstein JT. The new face of enterohaemorrhagic Escherichia coli infections. Euro Surveill. 2011;16(25):pii=19898. Available online: https://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19898
• Bielaszewsk, M et al. Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. Lancet Infectious Diseases. Published Online June 23, 2011 DOI:10.1016/S1473- 3099(11)70165-7
• Frank, C et al. Epidemic Profile of Shiga-Toxin–Producing Escherichia coli O104:H4 Outbreak in Germany — Preliminary Report. NEJM June 22, 2011 (10.1056/NEJMoa1106483).

E. coli: PHIL/CDC