E.coli O157 & Haemolytic Uraemic Syndrome

Possible breakthrough in the treatment of E.coli

21st September 2011

The European Food Safety Authority (EFSA) has revised its consumer advice on the consumption of sprouts and sprouting seeds.

Following the E.coli outbreak in France and Germany earlier this year, the EC has informed EFSA that the EU member states have now completed tracing activities across the food chain.

With the removal from the market in all member states of the most likely source of the contaminated food, a specific lot of fenugreek seeds from Egypt, coupled with on-going importation restrictions, the authority is no longer advising consumers not to grow sprouts for their own consumption and also not to eat sprouts or sprouted seeds unless they have been cooked thoroughly.

EFSA recommends that consumers refer to national food safety agencies for any specific advice regarding sprout consumption.

The authority takes this opportunity to remind consumers of the importance of good hygiene practices when preparing and consuming fresh vegetables, such as washing hands before food preparation, washing food properly under running potable water and separating raw foods from ready-to-eat or cooked foods.

An outbreak of an E.coli O157 emerged across Britain in December 2010, and cases continued to emerge until July of this year, but only now at the end of September 2011 when the outbreak appears to have come to an end, has the public been told.

The Health Protection Agency (HPA), Health Protection Scotland and Public Health Wales received reports of 250 cases of infection with a particular subtype of E. coli.O157 known as Phage Type 8 (PT8) distributed across England, Scotland and Wales. The majority of these cases were mild to moderate but 74 people were assessed in hospital. Four developed Haemolytic Uraemic Syndrome (HUS) and one patient with underlying health problems died.

This outbreak was not related to the outbreaks in Germany or France earlier this year which were caused by a different strain of E. coli called O104.

Joint investigations with the Food Standards Agency (FSA) found that people who were ill with this particular strain of E. coli O157 infection were statistically more likely to have lived in a household where leeks sold loose (i.e. not prepacked) and potatoes bought in or sold from sacks had been handled, than those who had not. There was no evidence to suggest any particular retail source or variety of the produce was responsible for people becoming ill. Illness appears to have been caused by traces of soil carrying the E. coli O157 bacteria present on the vegetables.

Dr Andrew Wadge, Chief Scientist at the Food Standards Agency said: "It's sadly a myth that a little bit of dirt doesn't do you any harm; soil can sometimes carry harmful bacteria and, although food producers have good systems in place to clean vegetables, the risk can never be entirely eliminated. Control of infection from E. coli O157 relies on an awareness of all potential sources of the bacteria and high standards of hygiene where it may be present.

"This outbreak is a timely reminder that it is essential to wash all fruits and vegetables, including salad, before you eat them, unless they are labelled 'ready to eat', to ensure that they are clean. It is also important to wash hands thoroughly as well as clean chopping boards, knives and other utensils after preparing vegetables to prevent cross contamination."

Dr Adak from HPA, added: "It's important to remember that the risk of contracting E. coli O157 in these circumstances is very small compared with the huge benefit of eating plenty of vegetables. But E. coli O157 is a serious infection that can cause significant harm, and the public can protect themselves by taking simple but essential precautions such as preparing raw vegetables safely.

The following FSA advice applies to all food preparation and will also help reduce the risk of infection:

Preliminary data presented last week at the 51st Interscience Conference on Antimicrobial Agents & Chemotherapy (ICAAC) suggests that patients in last springs outbreak of E.coli O104:H4 in Germany responded well to Azithromycin (Zithromax).

Johannes Knobloch, MD, of the University of Luebeck, said that a retrospective analysis of patients from north western Germany found that those receiving azithromycin (given prophylactically to patients with severe illness for meningitis prevention) had cleared the pathogen by the end of the standard-10-day treatment period.

In contrast, more than half of those not receiving azithromycin continued to shed the bacterium in stool weeks after the initial onset of illness.

Moreover, early results from a follow-up prospective study in which long-term carriers of E.coli O104:H4 received a short course of azithromycin indicated that 14 of 15 patients had cleared the pathogen, Knobloch said.

Azithromycin has not previously been considered a first-line weapon against enterohemorrhagic E. coli strains such as O104:H4 that produce Shiga toxin.

Knobloch said north western Germany was essentially ground zero for the outbreak, which was traced to contaminated sprouts. About 4,000 people across Europe fell ill and more than 50 died.

Some 300 people were treated at the University of Luebeck's hospital, he said, with 103 eventually confirmed to have the E.coli O104:H4 strain. Of these, 57 had haemolytic uraemic syndrome (HUS), one of the more severe consequences of the infection, with 35 receiving eculizumab (Soliris) as a therapy to prevent kidney failure.

Because eculizumab creates a risk for meningococcal infections, German guidelines suggest prophylaxis with azithromycin, which was given in 22 cases, Knobloch explained. The treatment typically started a week or two after symptom onset.

Another 43 patients without HUS, who had a minimum of two stool samples collected and analyzed at least four weeks after initial symptom onset, were included as a control group.

In all the patients receiving azithromycin, stool samples were negative for E.coli O104:H4 by the end of treatment or within a few days afterward. At day 30 after symptom onset, none of the azithromycin group was shedding the pathogen.

At day 42, on the other hand, 58% of patients in the control group were showing stools positive for the organism (P<0.001).

Knobloch said the difference was not related to HUS status. About one-third of patients in the control group also had HUS, but the mean time to E.coli clearance was no shorter in those patients than in those without HUS (28.9 versus 31.1 days, P=0.97).

He said these findings prompted the question of whether azithromycin could be used to decolonize patients who continued to shed the E.coli O104:H4 pathogen weeks after initial infection.

There has been concern that antibiotics can stimulate toxin production by enterohemorrhagic E.coli strains, he indicated. But some studies had shown that is not the case with azithromycin.

A prospective, uncontrolled trial is now underway in Luebeck, and Knobloch presented results from the first 15 patients. These patients had been infected for a mean of 48 days and were still symptomatic enough to have restrictions on daily activities. The treatment consisted of 500 mg/day of azithromycin for three days.

Stool samples from all 15 patients were negative within several days of completing the treatment. In one patient, however, stool samples became positive again after about two weeks. Knobloch said it was unclear whether the infection was recurrent or whether the patient was re-infected with the pathogen.

He ended his presentation by suggesting that azithromycin could be "a safe therapeutic option for the treatment of (Shiga toxin-producing enterohemorrhagic E.coli) diarrhoea to avoid development of HUS." But he emphasized that a prospective trial would be necessary to confirm the potential.

It may be too early to hope that these findings are the beginning of a much longed for breakthrough in the treatment of E.coli, but HUSH hope further research will be on-going.

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