EHEC: A wave of infection from the north

20. June 2011

Since May 10 a wave of a particular type has been rolling from north to south: infection from EHEC intestinal bacteria is spreading throughout Germany and Europe. Meanwhile, over 3000 Germans have become sick, a number of deaths has been reported by the authorities. They recommend basic hygiene rules – therapeutically speaking, there is little that can be done.

Escherichia coli is a coloniser of the large intestine of humans and animals, one evil stepdaughter of whom – the enterohemorrhagic Escherichia coli (EHEC) – carries additional genetic elements on board which give it pathogenic properties. Dr. Rolf Steinmüller of the Scottish Neogen Corporation has rated it as “one of the greatest microbiological challenges to the food industry since botulism” – particularly as raw meat, unpasteurized dairy products and fruit and vegetables are regarded as sources of infection. Bacteriologists categorise EHEC with the label O157:H7. “O” describes specific lipopolysaccharides – that is, sugars and fats – in the membrane, and “H” defines genetic properties of the flagella. Other variants are also known.

Sherlock Holmes in a white coat

Employing detective instincts, scientists from Berlin’s Robert Koch Institute (RKI) are pursuing the source of these infections. They have been interviewing patients and analysing their food intakes.

EHEC infections are not rare – since the introduction of mandatory reporting in Germany in 2001, authorities have registered every year between 800 and1200 cases of illness. The bacterium therefore is, according to experts, considered the second most common pathogen of inflammatory gastrointestinal diseases. Only Salmonella can top these numbers. Severe cases were however, outside of the usual risk groups, the exception. Experts are especially surprised this time that many adults – often women – are affected. “Classically, it’s school children on a farm,” says RKI-spokesperson Susan Glasmacher. She considers the severity of cases also not to be typical. “This development exceeds any historic measure,” warns microbiologist Professor Dr. Werner Solbach of the University Hospital Schleswig-Holstein.

Caution: free-roaming bacteria

Ruminants – cows, goats or sheep – are often found to be ‘guilty as charged’. Veterinarians suspect that it is particularly cereals given to animals that really only eat grass or hay, which interferes with the intestinal environment, so that EHECs are able to establish themselves. Such use of feed has been common since the 1980s, in parallel to that one finds in the literature the first reports of infections. After elimination, the bacteria remain active in the environment for a few weeks. If bacteria manages to get via manure onto foods that are eaten raw and unwashed, the outcome is disease. For that to happen, about 100 bacteria is enough. Meat and milk also may be contaminated by unclean processing.

After the meal, the journey begins in the digestive system. Via a special adaptation system – making it invulnerable to hostile gastric acids – EHEC makes its way without obstacle into the intestine. After a latency period of about one to three days there is severe, bloody diarrhea accompanied by cramping abdominal pain, nausea and vomiting.

Somatic cells reprogrammed

Once the destination is reached, EHEC hooks itself with the help of special proteins into the intestine. Researchers at the Helmholtz Centre for Infection Research (HZI) investigated these mechanisms: in particular the cellular “corset“, i.e. actin, is reprogrammed by the invader cells. Protuberances arise, onto which the intruders can effectively cling. Even with severe diarrhea, they remain in the intestine and won’t be flushed out. “The foundation to this signal transduction process is a specialised secretion system – a kind of molecular syringe – through which the bacteria injects whole proteins into the host cell,” says cell biologist Professor Dr. Theresa Stradal. The crucial elements here are the factors Tir and EspFU. Tir is presented on the surface of the host cell and a bacterium can then dock onto it. EspFU however gives the ‘go-ahead’ to rebuild the skeleton of the intestinal cells. The feedback takes place via another molecular link, so that the rebuilding of actin structures is frequently shared at these sites with bacteria.

Fixed in that way, EHEC pumps the killer protein Verotoxin directly into the lumen of the intestine. This substance is – alongside botulinum toxin – one of the most powerful natural poisons. Verotoxin inhibits the synthesis of proteins in the cell and leads to the demise of the affected tissue. Via passage through blood vessels or lymphatics, numerous organ systems could become affected, such as the kidneys, the large intestine, the nervous system or the pancreas. The toxin seems to be specifically targeted at the small blood vessels of the glomeruli. Their destruction leads to Hemolytic-uremic Syndrome, according to studies up to ten percent of those infected are so affected. If a laboratory test shows anemia due to depletion of red blood cells and the number of platelets has also decreased, medical practitioners assume a thrombotic thrombocytopenic purpura. In some patients the lining of the colon becomes inflamed, known as hemorrhagic colitis.

Inform patient – avoid panic

For these patients there is little that medical practitioners have to employ against it: according to the guidelines “Acute infectious gastroenteritis” no antibiotics should be administered. Success is, as a consequence of resistence, more than problematic, and an elevated release of toxins can’t be excluded. Instead, the focus is on dealing with symptoms – electrolytes are indicated in diarrhea, and patients with acutely negative developments have to be treated as in-patients. In an instance of hemolytic-uremic syndrome, one can’t avoid forced diuresis or dialysis. One thing that should not be overlooked: even patients who have recovered can still over several months in some cases discharge infectious germs. Strict rules should be put in place in order to prevent them from spreading the infection in the family or the workplace.

There still remains preventative action: epidemiologists from the Federal Office for Risk Assessment (BfR) have developed guidelines for patients. Alongside obvious hygiene measures such as hand-washing, they advise strict hygiene in the kitchen – cutting boards made of wood and cloth are considered havens for uninvited guests. And fruit and vegetables should be washed; raw meat products are at present to be deleted from the diet completely. “Because EHEC bacteria occurs especially in ruminants, milk and meat of these species have to be sufficiently heated before consumption,” advises BfR President Professor Dr. Dr. Andreas Hensel. The familiar saying “Peel it, boil it, cook it – or forget it” in 2011 hasn’t suffered a loss of relevance either.

But the support of medical colleagues is also requested: BfR encourages doctors to immediately have an EHEC detection test run for those with bloody diarrhea. If the test is positive, it is a duty to send a report to the appropriate health authorities. Then samples should go as well to the National Reference Center for Salmonella and other enteritis pathogens in Wernigerode.

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David Hodgson
David Hodgson

On the whole, well written but, what does he mean by “sufficiently heated”? Where did the outbreak originate?

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Is anything known yet about the origine of the ‘additional genetic elements?
Could there be any truth in the accusation as made on

#1 |

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