Want to know more about the origin of Shigatoxin-producing E. coli?

 Bill Marler is a very rare individual: he is a lawyer with an ability to grasp the principles of microbiological food safety and to write about them in a way that is accessible to the general public.  Bill has been closely involved in food borne illness litigation since 1993, when he obtained a $15.6 million settlement for Brianne Kiner, a nine year old girl who suffered HUS and ultimately kidney, liver and pancreas failure after eating Jack-in-the-Box hamburger.  He has become a fiercely active food safety campaigner.

Recently, Bill conducted a literature review on the origins of Shigatoxin-producing Escherichia coli  and has published the first two parts on his food safety blog.  These publications are well worth reading - they are not written in highly technical language, but the reference list allows those readers sufficiently interested and capable to follow up his sources and read the original material.

Links to the first two parts are shown below:

http://www.marlerblog.com/lawyer-oped/where-the-hell-did-shiga-toxin-e-coli-come-from-a-literature-review---part-1/

http://www.marlerblog.com/case-news/where-the-hell-did-shiga-toxin-e-coli-come-from-a-literature-review---part-2/

There is just one problem with this review; Bill has taken away my option to set such a study of literature as an assignment for my postgraduate students in my course "Frontiers of Food Microbiology".  The students will still be expected to read and discuss the material, but I can't use their reviews for assessment purposes.  Thanks Bill!

Haemolytic Uraemic Syndrome

In the wake of infection by Shigatoxin producing Escherichia coli (STEC), some patients develop Haemolytic Uraemic Syndrome (HUS).  The recent outbreak of O104:H4 STEC in Europe resulted in an unusually high proportion of patients going on to develop the syndrome, some of whom succumbed to the infection.

Drew Falkenstein, an associate of Marler Clark law firm in Seattle, has written a very well informed article on HUS.  Rather than write another, I suggest that interested readers follow the link to Drew's posting on Food Poison Journal.

Colonel Mustard, in the Dining Room, with the Sprouts

The last couple of weeks have been like the old game of Cluedo, with everyone running round accusing various participant of foul play and trying to find the culprit.  It would be amusing if it were not so deadly serious.

It now appears that the outbreak of Escherichia coli O104:H4 in Germany, which has now reached 16 countries, was probably caused by fresh vegetable sprouts grown in a farm in Uelzen, near Hamburg.  Unfortunately,  cucumbers from Spain, lettuces and tomatoes also had the finger pointed almost indiscriminately at them.  That caused huge financial losses for the suppliers and had knock-on effects on vegetable sales throughout Europe.  In some ways, I can sympathise with the authorities and the media.  This is one of the largest and most serious outbreaks of food poisoning ever and finding the source as quickly as possibly was imperative.

At the time of writing, there have been 3517 cases of EHEC infection, resulting in an unprecedented 839 cases of Haemolytic Uraemic Syndrome and 39 deaths.  The rate of new case reporting has slowed, but it is likely that more people will become ill before this is all over.

This shows just how difficult it is to pinpoint the source of an outbreak of food poisoning in our highly integrated and widespread food supply chain.  The sprout farm purchased seeds for sprouting from both European and Asian countries.  The seeds were sprouted, using what seems to be standard and well designed conditions, and the 18 different sprout mixtures were sent to many different points in Germany.

The German authorities have been accused of being in disarray and having no proper response prepared.  There may be some truth in this - if the responsibility for food safety is spread across many local authorities and agencies, setting up a coordinated and timely response is fraught with difficulty.  But it is generally recognised that epidemiological investigations may have a success rate as low as 33% in tracking down the source of infections and the chance of success falls as time goes on.

At times like this, we often hear calls for increased testing of products before they are released onto the market.  Good try, but no cigar!  For a number of reasons, microbiological testing to assure safety of food is just not possible.  Testing is expensive and time consuming.  In some cases, the testing period exceeds the shelf life of the product.  A simple statistical calculation shows that when contamination levels are low, the number of samples that must be tested to get even a 95% chance of detection is prohibitively large and even then, 5% of contaminated samples will be accepted as safe.  Testing for E. coli O157:H7 would not have picked up the German strain and even proposed widened testing for "The Big Six" Entero-Haemorrhagic E. coli strains would have missed this one.

Regulators must be strong in the coming months.  Microbiological testing gives only a retrospective view and a poor one at that.  Imposing increased mandatory testing will not assure the safety of foods.

The only way we can ensure the safety of our food supply is to introduce controlled lethal steps in processing, such as heating or irradiation, or to put in place rigorous control of every potentially hazardous ingredient, process step, processing facility and distribution chain.  This is particularly important with high risk products such as sprouts.  What every food producer and distributor needs is a Hazard Analysis based Food Safety Programme of Risk Management.

Evolution in action

Over the last three weeks, a rare form of Escherichia coli has made an appearance in Germany.

E. coli is a normal inhabitant of the gut of man and animals and is found there in very large numbers.  They are mostly harmless and actually help us by producing vitamin K.  However, some strains are pathogenic and cause diarrhoea.

Individual strains are recognised by their antigenic signature. The antigens are found on the surface of the cells, on the flagella and in the capsule that surrounds the cells.  Thus one of the strains that hits the news quite frequently is referred to as O157:H7.

The strain now causing havoc in Europe is E. coli O104:H4.  This has rarely been seen as a cause of disease.  However, the current outbreak is shaping up to be one of the most dangerous ever seen.

Why has this happened?

That's a question that none of us can answer yet, but the information on this strain is growing rapidly.  It can produce a very damaging toxin, called Shigatoxin.  The bacterium causes bloody diarrhoea, which is bad enough in itself.  But bacteria producing this toxin can also go on to produce Haemolytic Uraemic Syndrome, normally affecting around 2 to 10% of patients, who are often very young or immunocompromised.  However, O104:H4 appears to be very virulent and around 30% of patients, who were not in the high risk group, have developed this life-threatening syndrome.  So far, 18 people have died.

The fact is, bacteria evolve very rapidly.  We see one strain develop resistance to an antibiotic and soon other strains become resistant too.  This happens because bacteria can  exchange genetic information by a number of different mechanisms.  The rate of mutation might be very small, perhaps one in 10 million replications produces a mutant and most of these mutations are probably lethal.  However, a single cell can potentially produce a population of around 17 million cells in 8 hours.  That allows for a lot of mutations.  If even one of these mutants has some advantage over the rest of the population, or at least no disadvantage, the mutation will spread through the population.

This might surprise you, but bacteria also suffer from virus infections.  These viruses, or bacteriophages, invade the cells and cause them to make more virus particles before bursting open to restart the infection cycle.  Occasionally, the new virus particles contain a bit of bacterial DNA and transfer it to the next host.  Sometimes, whole genes can be transferred.

It appears that O104:H4 has not only the Shigatoxin gene, almost certainly transferred by bacteriophage, but has also picked up some other virulence factors.  This is why it is so dangerous - the toxin is very damaging to human cells, particularly in the kidney, and the bacterium appears very capable of initiating infection.

I believe we are seeing evolution in action.  A normally benign bacterium has become a killer.