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O104:H4 May Change How We Deal With E. coli

With recent estimates attributing the ongoing German E. coli outbreak to 3,406 illnesses and 39 deaths, it has become the deadliest — and second largest — E. coli outbreak in history. And while already singular in its impact, the outbreak sets itself farther apart in that its infections have resulted not from the infamous E. coli strain O157:H7, but O104:H4, a rare strain never before linked to a large foodborne illness outbreak.

In the weeks following the outbreak’s onset in Germany, an unprecedented collaboration of scientists worldwide have taken to studying O104, analyzing its genes to compare it to other strains and better understand its underlying characteristics. Jorge Girón, Ph.D., E. coli researcher and associate professor of microbiology at the University of Florida’s Emerging Pathogens Institute, believes this outbreak could lead to significant adjustments in how both agriculture producers and healthcare providers deal with E. coli.

What most predominantly differentiates O104 from O157 is its adoption of numerous traits not typically found congregated in one strain: Not only does it produce the noxious Shiga toxin of the virulent enterohemorrhagic strains, it also possesses defensive enteroaggregative traits –a combined mouthful of properties much more difficult to tolerate physically than verbally.

The term “enteroaggregative” refers to sticky strains of the bacteria that group together –aggregate — into a “stacked-brick pattern” and cling to intestinal tracts. Once there, they induce heavy mucus production in their host’s intestines, which they then use for both protection and sustenance.

Enteroaggregative E. coli are known to cause persistent diarrhea, but are historically unrelated to hemorrhaging and hemolytic-uremic syndrome (HUS), the acute kidney disease caused by Shiga toxin-producing enterohemorrhagic E. coli.

O157 is enterohemorrhagic, but not enteroaggregative. The bacteria do not aggregate together, but they possess cell structures that help them adhere to intestines, where they produce the Shiga toxin known for inflicting HUS and making E. coli a household name among pathogens.

By comparison, O104 clumps together and spurs mucus production for protection while also releasing Shiga toxin into the bloodstream, an adaptation that has resulted in at least 826 cases of HUS in this outbreak.

As Ross Anderson reported for Food Safety News two weeks ago, this outbreak’s ratio of HUS cases — now roughly one in four — is alarmingly high, at least for the time being. HUS cases among O157 infections generally average closer to one in 10.

 

Though Girón cautioned it is too early to tell if O104 is truly more virulent than O157, he said O104’s nasty combination of traits likely gives it the edge.

“The mucus production explains why these bacteria are so persistent,” he said. “It’s very hard for the immune system to get rid of them while they’re embedded in the host material, and it could be that the bacteria are releasing the toxins without even being attacked.”

O104 is not the first known strain with this particular résumé of traits — a similar strain known as O111:H2 caused a small outbreak in France in 1992 — but it has by far caused the greatest impact, and it distinguishes itself even further in the victims it affects.

Girón voiced special concern in the fact that O104 has predominantly caused HUS in adults, when children and the elderly are historically the main victims of Shiga toxin-producing E. coli. On Tuesday, a 2-year-old boy became the first child to die from the outbreak, which has killed 37 adults — mainly women.

Thus far, no clear explanation for this discrepancy has surfaced, though it might be partially related to eating habits, with children less likely to eat the sprouts that have been implicated as the source of the outbreak.

Numerous other commentators, including “Superbug” author and blogger Maryn McKenna, have brought up O104’s extensive list of antibiotic resistances, citing it as an enormous –though tangential — public health concern. Physicians know not to prescribe antibiotics for O157 infections because the sudden killing of the bacteria can release HUS-inducing and potentially deadly amounts of Shiga toxin.

As Girón pointed out, that fact could have created one major problem in the early development of the outbreak: It is likely that German hospitals were only screening the first enterohemorrhagic E. coli symptoms for O157 and not O104, which no one would have suspected before news of the outbreak spread.

“When people come into a hospital with bloody diarrhea, they would normally assume it’s O157 and not give antibiotics to the patients,” he said. “In this case, because it wasn’t O157, the physicians might have thought it was okay to give antibiotics, not knowing that O104 would produce the Shiga toxin.”

This potential misunderstanding over antibiotics might at least partially explain the high rate of HUS among the ill. Girón said this outbreak may necessitate new screening procedures at hospitals to account for O104 alongside O157, ensuring patients don’t receive antibiotics that could exacerbate their illness or kill them.

In regard to its environmental origins, O104 takes after the more-prevalent enteroaggregative E. coli in that only humans are its host, not cattle or other ruminants. It can spread through contact with objects in the environment, water, food, or human fecal matter.

As a final caution, Girón warned that only sufficient cooking can eliminate E. coli from vegetables. Just weeks ago, he and several colleagues published a study showing that E. coli can infiltrate and survive in the inner tissues of spinach after industrial washing techniques and thorough washing in kitchens.

“If vegetables are contaminated with E. coli, the only way to absolutely make sure they’re safe is to boil or cook the plant. That’s something we’re just now starting to understand,” he said. “All of this is going to change how produce is treated at the industrial setting.”

© Food Safety News
  • hhamil

    My thanks to James Andrews and FSN for bringing together all of this information into a single article.
    It contains so much that is new to me and so important, I want to make certain that I’ve understood 2 parts of it correctly.
    First, is it correct that the ultimate source of the O104:H4 contamination in Germany must have been human?
    Second, is Dr. Giron saying that some physicians treating those sickened by O104:H4 may have inadvertently caused their patients’ to have HUS and a more serious illness by prescribing antibiotics because they didn’t realize what they were up against due to O104:H4’s rarity and the limited understanding of how it attacks humans?

  • Harry Hamil

    My thanks to James Andrews and FSN for bringing together all of this information into a single article.
    It contains so much that is new to me and so important, I want to make certain that I’ve understood 2 parts of it correctly.
    First, is it correct that the ultimate source of the O104:H4 contamination in Germany must have been human?
    Second, is Dr. Giron saying that some physicians treating those sickened by O104:H4 may have inadvertently caused their patients’ to have HUS and a more serious illness by prescribing antibiotics because they didn’t realize what they were up against due to O104:H4’s rarity and the limited understanding of how it attacks humans?

  • doc raymond

    Harry, I am no expert on E coli L104:H4, but then not very many are. What i do know in response to your two questions is as follows.
    1. O104:H4 has not been found in ruminants’ intestines. That is not to say it won’t be, because it is so rare not much testing has been done to date. The EaggEC component is what may separate it from the EHECs as for as the host component goes.
    2. The implication in this piece is that patients may have been treated with antibiotics as the Docs were thinking, based on test results, that this was not an E coli infection. Treating E coli with antibiotics can cause increased release of Shiga toxin, making the illness worse.

  • jandrews

    Hi Harry,
    I apologize for the delay, but I asked Dr. Giron if he would like to respond to your questions. Here’s what he said in an email:
    “I don’t know the details of the people who died, if they received antibiotics or not, if they did, it is probably because of what we discussed and you wrote well, the doctors did not know they were dealing with a Shiga toxin-producing E. coli.
    It is possible that this new strain is far more virulent than the typical E. coli O157:H7 and killed people more quickly. More research has to be done with this new O104:H4 strain.
    Regarding the first question, EAEC are generally associated with human infections and they can be found in the environment. Where the O104 isolate that acquire the bacteriophage carrying the Shiga toxin genes or came from it is not known, we can only suspect it is human.
    The O104 strain is genetically similar to an EAEC strain that came from Central Africa to France (I believe). Eventually, people will trace back, employing genetic tools, where this strain came from.”

  • James Andrews

    Hi Harry,
    I apologize for the delay, but I asked Dr. Giron if he would like to respond to your questions. Here’s what he said in an email:
    “I don’t know the details of the people who died, if they received antibiotics or not, if they did, it is probably because of what we discussed and you wrote well, the doctors did not know they were dealing with a Shiga toxin-producing E. coli.
    It is possible that this new strain is far more virulent than the typical E. coli O157:H7 and killed people more quickly. More research has to be done with this new O104:H4 strain.
    Regarding the first question, EAEC are generally associated with human infections and they can be found in the environment. Where the O104 isolate that acquire the bacteriophage carrying the Shiga toxin genes or came from it is not known, we can only suspect it is human.
    The O104 strain is genetically similar to an EAEC strain that came from Central Africa to France (I believe). Eventually, people will trace back, employing genetic tools, where this strain came from.”