E. coli update: no positive sprouts so far

Well, Sunday the said we’d have some results on the sprout tests for E. coli O104:H4. Well, so far the results are negative.

The 1st tests from a north German farm suspected of being the source
of an _E. coli_ [O104:H4] outbreak are negative, officials say. Of 40 samples from the farm being examined, they said 23 tested negative.

Officials had said earlier that bean sprouts produced at the farm in Uelzen, south of Hamburg, were the most likely cause of the outbreak. The outbreak, which began 3 weeks ago and is concentrated in Hamburg, has left 22 people dead. Initially, German officials had pointed to Spanish cucumbers as the probable cause of the illness.

The moderator notes that just because the ones being tested are negative, it doesn’t rule out the farm as the source of the outbreak. Perhaps all the contaminated sprouts are gone, and if it was something wrong at the farm (contamination of the water by sewage or something similar), it may have resolved itself. Nevertheless, after the false start with the Spanish cucumbers, it would certainly be nice to get some kind of confirmation. Apparently the tests on the remaining 17 samples are still pending so it remains to be seen if there will be any proven connection, but it’s looking less likely. If they don’t find anything definitive, officials are going to have even more egg on their faces.

While the human cases seem to be slowing down, this is going to be bad if the source can’t be identified–and that gets more difficult to do every day that passes.

E. coli update: sprouts as the culprit?

The E. coli story is moving quickly. A news report out today suggests that sprouts might be the culprit (though it should be emphasized that the outbreak strain hasn’t been isolated from these vegetables yet):

Mr Lindemann said epidemiological studies all seemed to point to the plant nursery in Uelzen in the state of Lower Saxony, about 100km (62m) south of Hamburg – though official tests had not yet shown the presence of the bacteria there.

“Further evidence has emerged which points to a plant nursery in Uelzen as the source of the EHEC cases, or at least one of the sources,” he said.

“The nursery grows a wide variety of beansprouts from seeds imported from different countries.”

As far as the molecular analyses, Kat Holt and David Holme have been doing some additional analyses of the released genome sequences, and it looks like this is an old strain of enteroaggregative E. coli (the type which usually cause more run-of-the-mill diarrhea; free review here, but it’s a bit dated) which has simply acquired the Shiga toxin. From Kat:

It will be interesting to see what more can be found as the assemblies of the strains are improved with additional data. While the analysis so far suggests that this is a classic case of E. coli sharing genes via various mechanisms of horizontal transfer (i.e. bacteria doing what bacteria do), it will be very interesting to tease out the subtleties of the virulence genes and how they interplay to result in this particularly virulent bug.

For me, another interesting unanswered question will be the origin–if it’s on the sprouts, how did it get there? Are animals in the area carrying this? Why so many antibiotic resistance genes? Still quite a bit to learn, even if the sprouts indeed turn out to be the vehicle.

E. coli O104:H4 in Europe–is it new?

Mike has has a great new post up looking at some molecular analyses of the current European outbreak strain. For anyone who hasn’t been paying close attention to what’s happening across the pond, there’s an ongoing outbreak of enterohemorrhagic E. coli (EHEC)–the type of E. coli that includes O157:H7, which has been associated with outbreaks of disease associated with food. The most infamous outbreak was the 1993 Jack-in-the-Box disaster, associated with undercooked hamburgers contaminated with the organism, but there have also been outbreaks associated with contaminated vegetables (such as the 2006 outbreak due to spinach). Infections with this bug can cause serious illness, including bloody diarrhea (due to production of a protein called the Shiga toxin) and eventually can shut down the kidneys. Permanent damage can result, and even death.

In most outbreaks, children have been the most affected group, and the outbreaks tend to be fairly small (as outbreaks go–~200 people were confirmed to be infected due to spinach in 2006, though many more mild or asymptomatic cases likely went undetected). That’s reason number 1 this European outbreak is a bit odd. Adults are the largest group affected, and of those, most have been women. It’s also a huge outbreak–at least 1600 affected and 16 deaths to date. Almost a third of those–roughly 500–have been diagnosed with hemolytic uremic syndrome (HUS), one of the most serious complications of the infection. That’s a huge number, and cases don’t seem to be slowing down, as we usually see with EHEC outbreaks.

News out yesterday also includes notice that one of the outbreak strains has been sequenced:

Meanwhile, a Chinese genomics laboratory, BGI (formerly the Beijing Genomics Institute), announced today that it has sequenced the outbreak strain and completed “a preliminary analysis that shows the current infection is an entirely new super-toxic E coli strain.” The analysis was done by BGI-Shenzen in collaboration with the University Medical Centre Hamburg-Eppendorf, the BGI statement said.

The analysis confirmed that the pathogen is an E coli O104 but said it is a new serotype, “not previously involved in any E coli outbreaks,” according to BGI. The strain is 93% similar to a strain found in the Central African Republic, but it has acquired sequences that seem similar to those involved in causing “hemorrhagic colitis” and HUS, the statement said.

The statement also said the E coli strain carries genes that confer resistance to several classes of antibiotics. Earlier reports from Europe had said the strain was resistant to multiple drugs.

A WHO official agreed that the outbreak strain is new, according to the AP report. “This is a unique strain that has never been isolated from patients before,” said Hilda Kruse, a WHO food safety expert.

Earlier this week, the CDC called the outbreak strain very rare but not brand new. In today’s AP story, Dr. Robert Tauxe, a CDC foodborne disease expert, said the strain was seen in a case in Korea in the 1990s. He said the genetic fingerprints of the current strain and the Korea one may vary slightly, but not enough to call the European strain new, according to the AP.

I believe that this is the Korean paper they’re referring to, describing a case of O104:H4 infection, but it’s not from the 1990s, at least that I can tell (published in 2006, though it may be an old case). Mike is skeptical that this is a new strain as well. The wording of the article doesn’t make sense either; O104:H4 *is* the serotype, so that obviously isn’t novel, though some elements of the bacterium could be. Reports are saying that it produces more toxin than ordinary EHEC strains, and that it’s resistant to multiple antibiotics. For these infections, the former is important; the latter, not so much, as treating EHEC infections with antibiotics actually makes the infection worse. (However, E. coli can also cause other types of infections, including meningitis and septicemia, for which antibiotics would be appropriate–so it’s not completely OK that it’s multi-resistant; it just doesn’t matter as much for the diarrhea/HUS combination).

So what’s going on? Still hard to tell. We don’t yet know the vehicle for bacterial transmission. Salad ingredients–lettuce, tomatoes, and cucumbers have been implicated in case-control studies but no one has yet found this strain on vegetables. We don’t really know if the virulence in this strain is higher than other EHEC strains, or if the higher apparent levels of HUS are due to better reporting/surveillance in Europe. (I think this unlikely–it’s a pretty large difference–but still, it needs to be examined). Basically, we’re closing in on a month into this outbreak and we still know very little, and it doesn’t seem to be slowing down at a rapid pace. And, we probably haven’t even identified all the cases to date–there have now been three diagnosed in the U.S. following travel to Germany, and likely more sporadic cases in other areas that haven’t been linked back to this outbreak yet. Stay tuned; this one’s going to be in the news for awhile as we get it all figured out.

Edited to add: see also other posts on this, especially the sequencing/novelty issues, here at phylogeo, here at bacpathgenomics, here at pathogenomics, or here at genomic.org.uk.

Swine flu update: Europe and the bottom of the world

For those of you looking to follow new cases (most of them suspected at this point, not confirmed), a great resource is HealthMap. Reports are popping up of possible infections worldwide: Scotland, Spain, Australia, and New Zealand. Certainly additional possible cases will be showing up over the coming days as well.

One thing I’ve seen mentioned (including here in the comments) is a question about the unlikelihood of a flu outbreak in Mexico in late April. Isn’t influenza a cold-weather bug? Well, yes and no. Influenza circulates year-round at a low level, but it lasts longer in the environment in colder temperatures with lower humidity, meaning more people can potentially be infected by each infected person, leading to our seasonal outbreaks. However, recall that in 1918 the first cases began in winter/spring 1918, and then it came back with a vengeance beginning in August, and really taking off by October. Additionally, we essentially have no barriers to worldwide spread, and there are already potential cases in New Zealand and Australia (where winter is setting in).

Again, we don’t know right now whether this will die out or become the next pandemic, but the spring timing of this doesn’t necessarily limit the virus’ potential.