Atypical Typhus

This is the third of 16 student posts, guest-authored by Mary Egan.

Murine typhus has been in the news recently in Austin, TX, where in May of this year, two people were found to be positive and one died.  This rings a number of alarm bells for me, since I live in Texas, and specifically in Austin.  I know of another Austin veterinarian who got sick with murine typhus in 2008, when it was first noticed in Austin and investigated by the CDC.  I was also working as a relief vet at the Town Lake Animal Center, the municipal shelter, and at the Austin Humane Society, the main nonprofit adoption shelter which has a feral cat Trap-Neuter-Return surgery clinic, when the CDC investigators came to Austin.  They collected blood samples on local animals and also fleas.  Of course, at that time I wasn’t particularly interested in public health, just shelter medicine, and it didn’t really register.  Now I wish I could’ve gone back and tagged along to see more of what they were doing!

Murine typhus is an odd and off the radar disease.  It doesn’t help that murine and typhus are both words with multiple meanings.  Murine is a word that refers to mice, in Latin, murinus, or mouse, in Latin, mus.  It is also a type of eye drops and also a brand of ear wax remover.  How putting mice in your eyes or ears helps them is a mystery to me.  Murine also sounds very similar to marine, so it’s not unreasonable to start picturing typhus near the ocean, which is an odd coincidence, since murine typhus actually occurs primarily in coastal areas.

Typhus itself is a confusing word.  It comes from the Greek, and means hazy, which is how your brain feels if you’re infected.  It is not the same as typhoid fever, which is caused by Salmonella typhi, a bacteria that can cause food borne illness resulting in diarrhea and vomiting.  This is not that.

The typhus we are interested in is a tiny bacteria from the family Rickettsia.  And of course there is more than one type of typhus, to confuse the issue further.  Epidemic typhus is the ancient disease that has been a major player in history.  It was first noted in the Spanish blockade of Granada in 1489, and then killed more of Napoleon’s army than the Russians.   This is Rickettsia prowazekii, which is carried on lice and affects humans.  This is the typical typhus.  If you ever read just “typhus” it is referring to this type of typhus.  It has also been called jail fever, since many old jails were breeding grounds for lice, and the prisoners were more likely to die of infection than be hung for their misdeeds.  This typhus can cause a rash, fever, severe headache, joint pain, kidney failure, delirium, stupor, and even death in 10-60% of cases if it’s not treated.  A blood test will show if there are antibodies to typhus if you go to your doctor with these signs.  There is an effective treatment, a course of antibiotics that kills the rickettsia, and supportive care depending on how far along the disease had progressed.  It is possible for the agent to go underground, and then reappear later in life.  Then it is called Brill-Zinsser disease and is often a very mild form of epidemic typhus, still treated with antibiotics.

The typhus that showed up in Austin is murine typhus, also called Rickettsia typhi, and it is carried on fleas and primarily affects rats.  This is also called endemic typhus because it is pretty much always present on rats in the environment.  Humans historically get it as a side product of coming into contact with rats carrying the infected fleas.  This disease is usually not as severe as epidemic typhus, but can still cause all the same signs and symptoms, and rarely can lead to death if not treated.  Less than 2% die of murine typhus if it is not treated with antibiotics.

Murine typhus has a worldwide distribution, but in the United States it is usually seen near coastal areas in California, Hawaii, and Texas.  The 2008 cases were odd that they were in Austin, in central Texas.   In the previous 25 years, there had only been four cases total.  In 2008 there were 13 cases in the four months from March to July, and a total of 33 cases by October.  Of these, 70% of the people infected were hospitalized with myalgia, severe headache, and fever, and the most severe cases were treated for pneumonia, kidney failure, and coagulopathy.   There were no deaths.  This outbreak showed that aside from the normal rat-flea cycle, there are likely other cycles that involve domestic and feral cats, opossums, dogs, and the fleas that live on them.  And consequently, the fleas that live on domestic cats and dogs then live in the yards and homes of their owners, and then can live on the owners themselves.

The cases were clustered in the central Austin area, with a large percentage coming from one zip code that contains a large portion of the exceedingly popular Town Lake Hike and Bike Trail used by over 20,000 people daily, and the smaller but more wild Shoal Creek Trail.  There have been reports of coyote sightings and suspected killings of family pets in this zip code.  So there is ample space for wildlife within this urban environment.  This also means there are plenty of hosts for fleas.  And Austin in general and this neighborhood in particular is known for a slightly hippy, crunchy granola lifestyle preferring organic and natural everything, with easy access to the outdoors and hiking trails.  It is not surprising this outbreak occurred in this area.

So what does all this mean?  Diseases which were previously uncommon are now becoming more common due to changes in lifestyle.  People want to live close to nature and have trails to walk their dogs.  There is nothing wrong with that.  It’s the parasite hitchhikers their pets pick up and bring home that’s the problem.  And changes in behavior where dogs are now not only in the house, but often in the bed with their owners, means that those fleas have a chance to bite humans.  That doesn’t mean you shouldn’t walk your dog on the trail.  But it does mean you need to use protection.  Spray yourself and your clothes with a flea killing insecticide such as DEET when out walking.  Wear boots, long pants, and long sleeved shirts.  Use appropriate flea control on your pets.  Kill fleas in your yard or home with appropriate premises control measures.  It’s great to be one with nature, you just don’t want that nature to bite back with a case of murine typhus.

Bibliography

1.  Adjemian J, Parks S, McElroy K, Campbell J, Eremeeva ME, Nicholson WL, et al. Murine typhus in Austin, Texas, USA. Emerg Infect Dis. 2010 Mar.   Accessed June 13, 2012.  Available at: http://wwwnc.cdc.gov/eid/article/16/3/09-1028.htm

2.  James C.  Two cases of typhus in Travis County.  KXAN web site.  Accessed June 13, 2012.  Available at: http://www.kxan.com/dpp/news/local/austin/2-cases-of-typus-in-travis-county

3.  Typhus.  Wikipedia website.  Accessed June 13, 2012.  Available at: http://en.wikipedia.org/wiki/Typhus.

4.  Murine typhus.  Texas Department of State Health Services website.  Accessed June 13, 2012.  Available at: http://www.dshs.state.tx.us/idcu/disease/murine_typhus/information/

5.  Conlon J.  The historical impact of epidemic typhus.  Accessed June 13, 2012.  Available at: http://entomology.montana.edu/historybug/typhus-conlon.pdf.

6.  Google map of 78703 zip code.  Google maps website.  Accessed June 13, 2012.  Available at: http://maps.google.com/maps?oe=utf-8&rls=org.mozilla:en-US:official&client=firefox-a&q=78703&um=1&ie=UTF-8&hq=&hnear=0x8644b55c47d7dc5f:0x717c8b7186632905,Austin,+TX+78703&gl=us&ei=i7DTT9vPJsLQ2AX54riFDw&sa=X&oi=local_group&ct=image&ved=0CHQQtgM

7.  Gonzales R.  Santa Ana announces flea-borne typhus alert.  Orange County Register website.   Accessed June 13, 2012.Available at: http://www.ocregister.com/news/santa-356066-control-typhus.html

8.  Roving pack of coyotes mauls pets.  KXAN website.  Accessed June 13, 2012.  Available at: http://www.kxan.com/dpp/news/local/austin/roving-pack-of-coyotes-maul-pets

Scarlet fever–past and present

While “flesh-eating infections” caused by the group A streptococcus (Streptococcus pyogenes) may grab more headlines today, one hundred and fifty years ago, the best known and most dreaded form of streptococcal infection was scarlet fever. Simply hearing the name of this disease, and knowing that it was present in the community, was enough to strike fear into the hearts of those living in Victorian-era United States and Europe. This disease, even when not deadly, caused large amounts of suffering to those infected. In the worst cases, all of a family’s children were killed in a matter of a week or two. Indeed, up until early in the 20th century, scarlet fever was a common condition among children. The disease was so common that it was a central part of the popular children’s tale, The Velveteen Rabbit, written by Margery Williams in 1922.

Luckily, scarlet fever is much more uncommon today in developed countries than it was when Williams’ story was written, despite the fact that we still lack a vaccine for S. pyogenes. Is it gone for good, or is the current outbreak in Hong Kong and mainland China a harbinger of things to come? More below…
Continue reading “Scarlet fever–past and present”

Hemolytic uremic syndrome (HUS) in history–part 3

I left off yesterday with the initial discovery of “Vero toxin,” a toxin produced by E. coli (also called “Shiga toxin” or “Shiga-like toxin”). Though this may initially seem unconnected to hemolytic uremic syndrome (HUS), the discovery of this cytotoxin paved the way for a clearer understanding of the etiology of this syndrome, as well as the mechanisms by which disease progressed. By the early 1980s, several lines of research pointed toward E. coli, and particularly O157:H7, as the main cause of HUS.

A 1982 Centers for Disease Control and Prevention MMWR report found a rare E. coli serotype, O157:H7, associated with hemorrhagic colitis following consumption of hamburgers. Similar results were reported in a 1983 Lancet paper, which found serotype O157 among their collection of verotoxin-producing strains. Another paper that same year from a Canadian group showed that O157:H7 was the second most common cytotoxic strain in their collection of over 2,000 E. coli isolates. The most common was serotype O26–more on that below. This paper also discussed an outbreak of hemorrhagic colitis that had occurred at a nursing home, with O157 identified as the cause. The evidence was mounting, but these were small studies and not always associated with HUS. Still, these papers collectively were suggestive of a connection between E. coli infection (especially with strains that produced the shiga/vero toxin), hemorrhagic colitis, and HUS.

In 1985, a new study came out which really helped to seal the deal. Rather than look only at cases in isolation, the authors designed a case-control study looking at patients with “idiopathic HUS” (in other words, HUS of unknown origin which started with diarrhea, rather than the other variant lacking this symptom). They ended up with 40 patients who qualified. They then picked a single control for each patient, matching them on age, sex, and season of the year. The controls were children either diagnosed with Campylobacter enterocolitis (and therefore, enterocolitis of a known cause) or were healthy children either from a local daycare center, or kids coming in for elective surgeries. Stools were collected from each group and tested for a variety of organisms, including vero toxin-producing E. coli (VTEC, also known as STEC for the shiga-like toxin nomenclature). They also tested for activity of the toxin itself in fecal samples. Finally, in the case patients, attempts were made to collect what are called “acute” and “convalescent” blood samples. These are samples taken when the patient is actually sick (“acute”), and then ones taken a few weeks later (“convalescent), to look at the presence of antibodies in the blood. If it was an infection by the suspected organism (in this case, STEC/VTEC), you should see a rise in antibodies the host produces that target the organism–for these kids, they were looking for antibodies to the shiga/vero toxin.

They found either vero toxin or VTEC in 60% of the case patients, but in none of the controls. Of the VTEC isolated, serotypes included O26, O111, O113, O121, and O157. For the latter, it was the most common type isolated (25% of the VTEC found). Of the patients who were negative for both VTEC and vero toxin, from those who had paired blood samples (12/16 of the remaining cases), 6 did show a rise in antibody titer against the vero toxin–suggesting they had been exposed and were producing antibodies to neutralize the toxin. So, for those keeping score, 75% of the cases had evidence of VTEC infection either by culture or serological techniques. It may not have been the nail in the coffin and there are certainly some flaws (the diversity of controls and lack of analysis of blood titers for the controls being two that pop out at me), but this paper went a long way toward establishing VTEC/STEC as the cause of HUS, which has been subsequently confirmed by many, many studies worldwide.

The most common vehicles of transmission of these organisms have also come into clearer focus since the 1950s, with almost all HUS/STEC outbreaks associated with food products; most common is still the O157:H7 serotype. O157 is a bit unique, in that this strain typically doesn’t ferment sorbitol–as such, this is often used as a diagnostic feature that sets it apart from “normal” E. coli. However, as I mentioned above (and as the current outbreak has shown), a number of other serotypes besides O157:H7 can also cause HUS. Most of these don’t appear to be as commonly associated with outbreaks–rather, they may more commonly cause sporadic disease where fewer people may become sick. Because these don’t have the unique sorbitol-non-fermenting feature, these may be overlooked at a diagnostic lab. There are assays that can detect the Shiga-like toxin directly (actually, we now know there are multiple families of related toxins), but not all labs use these routinely, so it’s likely that the incidence of infection due to non-O157 STEC is higher than we currently know.

HUS was once a mysterious, “complex” disease whose perceived etiology shifted almost overnight, as scientific advances go. What implications does this have for other diseases whose etiology is similarly described as HUS was 50 years ago? More on that tomorrow.

Hemolytic uremic syndrome (HUS) in history–part 2

As I mentioned yesterday, the epidemiology of hemolytic uremic syndrome (HUS) was murky for several decades after it was first defined in the literature in 1955. In the ensuing decades, HUS was associated with a number of infectious agents, leading to the general belief that it was a “multifactorial disease”–one that had components of genetics and environment, much like we think of multiple sclerosis today, for example.

Several HUS outbreaks made people think twice about that assumption, and look deeper into a potential infectious cause. A 1966 paper documented the first identified outbreak of HUS, which occurred in Wales. The researchers examined a number of possible environmental factors the patients may have had in common–including food, water, and various toxins–but came up empty. They sum up:

Since it is almost invariably preceded by a gastrointestinal or respiratory illness, it seems probable that it represents a response to an infection. Although Gianantonio et al. (1964) have identified one possible causative virus, it may be that various infective agents can initiate the syndrome.

This idea held throughout the next 20-odd years, as numerous studies looked at both environmental and genetic effects that may be leading to HUS. A 1975 paper examined HUS in families, suggesting that there may be two types of HUS (which we now know to be true–the genetic form is less often associated with diarrhea, and tends to have a worse prognosis as I mentioned yesterday). But still, no definitive cause for either.

There were also a number of studies testing individuals for many different types of pathogens. A 1974 paper enrolled patients in the Netherlands between 1965 and 1970, but one of the inclusion criteria was a “history of a prodromal illness in which gastrointestinal or respiratory tract symptoms were present.” The respiratory tract symptoms are mentioned in a number of papers, and were probably a red herring that sent people in search of the wrong pathogens for awhile. In this particular paper, they examined children for infection with a number of viral and bacterial pathogens, using either culture or serological methods (looking for antibodies which may suggest a recent infection). In that portion of the paper, they note a possible association with adenoviruses, but state that the data don’t support a bacterial infection–a viral etiology was deemed more likely. Regarding basic epidemiology, they did note a few small clusters of cases in families or villages, as well as a peak in cases in spring/summer–as well as an increasing number of cases from the first year of their study to the last. The epidemiology of HUS was starting to become clearer, and the syndrome appeared to be on the rise.

Even as additional case reports occasionally targeted foods as a precursor to HUS outbreaks, it wasn’t until the late 1970s and early 1980s that HUS really started to come into focus. In 1977, a paper was published identifying the “Vero toxin”–a product of E. coli that caused cytotoxicity in Vero cells (a line of African green monkey kidney cells, commonly used in research). Researchers were closing in.

German officials declare E. coli O104:H4 a sproutbreak

Via H5N1, German officials are calling it for sprouts:

Germany on Friday blamed sprouts for a bacteria outbreak that has left at least 30 dead and some 3,000 ill, and cost farmers across Europe hundreds of millions in lost sales.

“It’s the sprouts,” Reinhard Burger, the president of the Robert Koch Institute, Germany’s national disease centre, told a news conference on the outbreak of enterohaemorrhagic E. coli (EHEC) in northern Germany.

“People who ate sprouts were found to be nine times more likely to have bloody diarrhoea or other signs of EHEC infection than those who did not,” he said, citing a study of more than 100 people who fell ill after dining in restaurants.

As a result, the government lifted a warning against eating raw tomatoes, lettuce and cucumbers.

There still haven’t been any positive tests, but as I mentioned yesterday, the epi seems to strongly point to sprouts. Confirmation via bacterial isolation and typing would be ideal, but I’m not holding my breath for that to happen at this late date. Larger studies also, I’m hoping, will be done–the numbers above state that they came from ~100 people, out of approximately 3,000 sickened so far, and we still don’t know how the implicated sprouts were contaminated. Did it originate in the seeds? (If so, still from where?) Was it human-to-sprout contamination from a sick worker on the farm? (If so, where again did the worker pick it up?) Still so many unanswered questions, but at least this should let some of the other farmers’ lives get back on track.

The case of the missing smoking sprouts

Maryn McKenna has a great update today on the E. coli situation, looking at where we are as far as unanswered questions about the outbreak and the strain. It’s been a messy day; more evidence seems to point to the sprout farm, but CIDRAP also notes that another contaminated cucumber was found in the compost bin of a family sickened by the bacterium (this one had the correct serotype–O104), but it’s impossible to tell at this point whether the cucumber was the source of that bacterium or it ended up there from one of the sickened family members. Twists and turns abound in this investigation. I’ve not seen any confirmation that the remaining sprout isolates tested negative yet, either.

One thing I want to emphasize and expand upon, from the CIDRAP article:

Most of the investigation findings point back to a sprout source, and microbiological testing a month after the fact doesn’t change that, Hedberg said. “Negative micro results cannot negate positive epi results. This is an important principle that we cannot state too strongly.”

At this late date, it’s hard to say whether we’ll be able to definitively trace this back to its source–too much time may have passed for there to be any remaining contaminated source material left. This means we might not ever find the “smoking gun” (or smoking sprouts, as the case may be). With such a severe outbreak–725 cases of hemolytic uremic syndrome, over a quarter of those infected–that’s bad news if we can’t confirm the vehicle, as it may make it more difficult to find the ultimate source of this strain. However, as Hedberg notes, we do still have the epi. This was used long before we had today’s molecular typing techniques, or even before we had microbiology culture ability, for that matter. Think John Snow’s cholera investigations, where he didn’t even know about bacteria and yet was able to determine the water as the vehicle for infection. So while confirmation may not happen, it’s still looking like most lines of evidence point to the implicated farm.

Maryn also brings up a great point that what we’re seeing as far as cases may be over-estimating the actual severity of the infection. I’ve talked about this previously regarding influenza infections, particularly H5N1. Right now H5N1 has a high mortality rate–but is it artificially high, because mild or asymptomatic infections are being missed?

With O104, as with any food-borne infection, surely this is happening. Mild diarrhea or stomach cramping isn’t something people frequently go to their healthcare provider over, so inevitably cases are missed. However, it probably happens with any E. coli outbreak, yet in most others we still see HUS rates between about 2-7% of the confirmed infections, while this one is at about 26%. So it doesn’t seem (to me, at least) that missed mild infections are the whole story. Is this acting like the novel Clostridium difficile strains, which have a mutation in a regulatory gene that leads them to pump out higher levels of toxin than “regular” strains? More than just genetic analysis will be needed to investigate that–some basic microbiology will also be needed. If nothing else, this outbreak has given us much research fodder over the coming years.

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.