A Query about Q fever –Answers to the Questions you should ask

This is the tenth of 16 student posts, guest-authored by Jean DeNapoli. 

I own a small back yard flock of sheep and lambing season is the most exciting and rewarding time of the year.  Nothing is more enjoyable than watching a lamb who takes a few wobbly steps and nurses for the first time as her mother nickers encouragement.  Within a day, the lamb will be playing, bucking, running, and exploring her world.

Despite the pastoral wonders of the season, lambing is also inherently stressful.  I must constantly check the barn to monitor for birthing problems and help out when necessary.   This help might include repositioning a lambs stuck in the birthing canal, pulling a lamb when the ewe is unable to push it out herself, and cleaning the face and airway of a newborn when its mother is too exhausted to follow through on her own.  Shepherds all over the world share the same experiences that I do.  But what many of them don’t know is that they are probably being exposed to Q fever.

When the disease was first recognized it was given the temporary name Query fever (since very little was understood about it).  We now know it is caused by a bacteria called Coxiella burnetii.  It is found word wide and it is estimated that 15-20% of all cattle, sheep and goats have been exposed to it.  The livestock rarely show signs of illness, but it can contribute to reproductive problems such as abortions.

In an infected animal, the organism can be found in milk, urine, and feces.  But the greatest concentration of bacteria is in the amniotic fluid and placenta.  Ticks can spread the disease, but much more frequently, it is passed directly to other animals at the time of birth.  It can develop into a long lasting spore-like form and can then contaminate dust and be carried by the wind.  Q fever is very easily spread and it takes only one organism to cause disease!

Q fever is zoonotic; it can be passed from animals to people.  When people become infected, they may have fevers, headache and weakness.  Fortunately, the fatality rate is low (<2%).  But some people, especially pregnant women and those with heart disease or who are immune deficient, end up with a more chronic and severe disease.  Q fever may also cause pre-term delivery or miscarriage if women become infected while pregnant.

I am not only a shepherd, but I am a veterinarian and it surprises me that few shepherds (at least the hobby farmers I know) discuss Q fever or take the recommended precautions.  In research facilities, Q fever is a biosafety 3 organism (on a scale of 1-4), requiring special laboratory containment precautions. To put this in perspective, other level 3 organisms include tuberculosis, anthrax, SARS, and yellow fever.  Yet many farmers routinely assist in births without any thought to their own health.

Q fever is fairly common and can be difficult to detect in healthy animals, so experts recommend treating all sheep as if they are infected.  Pregnant women or women who may become pregnant should avoid working with sheep at lambing time.  Other people at increased risk (people with impaired immune systems and heart valve abnormalities) should also stay away from the barn at lambing time.

Shepherds should wear disposable gloves when assisting lambing or handling newborn lambs.  Masks should also be worn, especially in dusty conditions.   Farmers should not eat or drink in the barn and should clean their footwear and wash their hands when leaving the barn.

Clothes have also been shown to carry the organism and they are capable of causing infection in people handling the laundry.  Therefore, high-risk people should not handle clothing that has been worn in the barn until it has been cleaned.

Farmers should use good sanitation when handling birthing materials and bury or compost the placentas.  Birthing areas should be cleaned frequently and in a way that will not cause excessive dust.  It is very important that farmers understand biosecurity precautions in general and specific Q fever prevention protocols to keep themselves, their families and their neighbors safe.

Shepherds should also work closely with their veterinarian to keep their flock as healthy as possible.   In the event of an abortion, the fetal material (placenta) should be submitted to the veterinary diagnostic laboratory for testing.

But what if you are not a farmer, do you need to be concerned?  Well, you should at least be aware of the disease.

Although usually associated with farm animals, dogs and cats may also transmit Q fever to people, most commonly at and around the time of birth.  Again, people who are most susceptible should avoid association with pets at those times.  Coxiella burnetii has been found in milk, so dairy products should be properly pasteurized before being consumed.

The organism is easily transmitted through the air (it is even considered a possible bioterrorism risk for this reason).  The Netherlands had a recent outbreak of Q fever in people living close to goat farms due to unintentional airborne transmission.  However, the people who generally are at the greatest risk are farmers, veterinary workers and researchers.  They are the people most likely to be near animals giving birth or handling the organism during the course of their daily work.

With education and reasonable safety precautions, a visit to the barn does not have to be a risky event.  Through the simple sharing of information, we can keep future generations of farmers safe, healthy, and productive.


Prevalence of Coxiella burnetii infection in domestic ruminants:  A critical review.  Raphael Guatteo, Henri Seegers, Ann-Freida Taurel, Alain Joly, Francois BeaudeauVeterinary Microbiology 149 (2011) 1-16

Q Fever:  Current State of Knowledge and Perspectives of Research of a Neglected Zoonosis.  Sarah Rebecca Porter, Guy Czaplicki, Jacques Mainil, Raphael Guatteo, and Claude Saegerman.  International Journal of Microbiology Volume 2011 (p 1-22)

Eurosurveillance, special issue on Q fever, vol. 17, 19 January 2012

New York Department of health Q fever facts sheet (2011) http://www.health.ny.gov/diseases/communicable/q_fever/fact_sheet.htm

World Organization for Animal Health (OIE) fact sheet on Q fever (2011) http://www.oie.int/fileadmin/Home/eng/Media_Center/docs/pdf/Disease_cards/Q-FEVER-EN.pdf

Center for Disease Control (CDC) Q fever information (2011) http://www.cdc.gov/qfever/index.html

Public Health Agency of Canada pathogen safety data sheet for Q fever (2010) http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/coxiella-burnetii-eng.php

Health Protection Agency Q fever information for farmers (2010) http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1210834106356

University of Florida IFAS Extension, The Herd Health Handbook for Goat Producers:  Biosecurity at the Farm Level, Ray Mobley and Carmen Lyttle-N’guessan.  (2009) http://edis.ifas.ufl.edu/famu006

Wyoming State Veterinary Laboratory, Q fever fact sheet (2004) http://www.uwyo.edu/wyovet/disease-updates/2004/files/qfever.pdf

Institute for Biosecurity, Saint Louis University School of Public Health, Q fever fact sheet (2001) http://www.bioterrorism.slu.edu/bt/quick/qfever01.PDF

Eurosurveillance Q Fever in the Netherlands: an up date on the epidemiology and control measures, W van der Hoek, et al. (2010) http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19520

Photographs are courtesy of Laura Cowperthwaite and Triple J Farm.

Wait, the infamous “Black Death” still plagues the United States?

This is the eighth of 16 student posts, guest-authored by Michelle Formanek. 

For many of us in the scientific world, particularly budding infectious disease epidemiologists like myself, the Plague (or, more dramatically, the “Black Death”) is a prime example of the rapid and devastating spread of an infectious disease. So devastating, in fact, that it wiped out nearly one-third of the population in Europe in the mid-1300’s. That’s roughly equal to 25 million people. It then persisted and has caused various outbreaks throughout history, most notably the Great Plague of London in which 1 in 5 residents died.

So why should be care about the Plague today? Isn’t that old news?

While I will go into more detail about the history of the plague a little later, I first want to mention what prompted me to write about what many people consider to be a no-longer-relevant disease. In order to gauge modern perceptions of the plague, I took a very unofficial survey of friends and family from various backgrounds about what they knew about the Plague. While the knowledge base ranged quite a bit, most were very surprised to hear that we still have cases of the Plague here in the United States.

Yes, you heard me right. The Plague still exists in the United States.

Of course, due to increased knowledge and antibiotic therapy, we no longer see the sweeping epidemic that caused so much turmoil throughout history. Nevertheless, an Oregon man is currently suffering from a rare case of the “Black Death.”

According to reports, a stray cat bit the unidentified man while he was trying to pull a mouse away from the cat. (I won’t even begin to speculate as to why this man was attempting to steal a mouse away from what was likely a very hungry stray cat, but that’s another story.) Several days later the man began to feel ill and presented to the hospital with symptoms typical of the Plague. These included fever, swollen lymph nodes and stomach pain. It has since progressed to bleeding mouth, nose and anus, and dying tissue.  Although the CDC has yet to confirm the diagnosis, all signs point to the Plague.

Only 10-15 people report becoming ill with the disease each year in the United States; this man is the fifth person in Oregon since 1995.

The Plague is caused by the bacterium Yersinia pestis., a rod-shaped bacillus that can live in various species of animals including rats, mice, squirrels, cats, prairie dogs, camels, and rabbits, among others. Yersinia pestis can then be transferred to humans through direct contact with infected animals, bites from fleas that have previously fed on infected animals (this is most common), or human-to-human through the air. Historically, the high population of small rodents and their flea friends in urban areas were attributed to the rapid spread of the disease.

While the Bubonic plague may be the most well known form of the disease, there are actually three different types of the Plague.  The Bubonic plague is the most common form and is characterized by buboes – painful, swollen lymph nodes – in the groin, armpit or neck. Septicemic plague occurs when the bacteria begins to spread in the bloodstream. Lastly, the most infectious form of the disease is Pneumonic plague. This advanced stage strikes when the bacteria can be passed from person to person through airborne droplets coughed up from the lungs. Bubonic plague is fatal roughly half the time, while Septicemic and Pneumonic are almost uniformly fatal without antibiotic treatment.

The man in Oregon was first believed to be suffering from Bubonic plague, but is now beginning to show signs of Septicemic plague, meaning it has entered his bloodstream and is able to reach all different parts of the body.  Luckily, antibiotics are effective in the treatment of the Plague if given early enough. Without antibiotics, 1 in 7 people infected end up dying.

So you may be asking yourself, as I did, where a deadly disease like this came from in the first place. The puzzling start of the epidemic went something like this:

“The Black Death arrived in Europe by sea in October 1347 when 12 Genoese trading ships docked at the Sicilian port of Messina after a long journey through the Black Sea. The people who gathered on the docks to greet the ships were met with a horrifying surprise: Most of the sailors aboard the ships were dead, and those who were still alive were gravely ill. They were overcome with fever, unable to keep food down and delirious from pain. Strangest of all, they were covered in mysterious black boils that oozed blood and pus and gave their illness its name: the “Black Death.” The Sicilian authorities hastily ordered the fleet of “death ships” out of the harbor, but it was too late: Over the next five years, the mysterious Black Death would kill more than 25 million people in Europe–almost one-third of the continent’s population.”

Unfortunately, the cause of the disease was not discovered until 1894, long after it swept through Europe with alarmingly high death rates. People had their ideas about what was causing the Black Death, but no one could actually figure it out. Some believed it was the spirit escaping the eyes of a sick man and infecting the nearest healthy person, others believed it was God’s way of punishing those who had sinned.  Citizens were so panicked that they went to extreme lengths to avoid contracting the disease, even so far as to completely abandon loved ones who got sick. More details here.

As mentioned before, antibiotics can be extremely effective in fighting this bacteria. As of right now, the Oregon man is still fighting for this life, but thanks to modern medicine, his chances of living are fairly high. The man likely contracted the disease from the cat; however, the cat died shortly after and its remains have since been sent to the CDC for testing.  Who knew that a stray cat in the Northwest U.S. could have possibly been harboring bacteria that once had the potential to wipe out entire cities. Fortunately, modern medicine is on our side.

So is the re-emergence of the Plague something that we should really be concerned about? Probably not. But it never hurts to be informed.











The emergence of “nodding disease”

The emergence of “new” diseases is a complicated issue. “New” diseases often just means “new to biomedical science.” Viruses like Ebola and HIV were certainly circulating in Africa in animal reservoirs for decades, and probably millenia, before they came to the attention of physicians via human infections. Hantavirus in the American southwest has likely infected many people, causing pneumonia of unknown origin, before the Four Corners outbreak led to the eventual identification of the Sin Nombre virus. Encroachment of humans into new areas can bring them into contact with novel infectious agents acquired via their food or water, or by exposure to new disease vectors such as mosquitoes or ticks. Occasionally, emerging diseases may be truly “new”–such as recombinant influenza viruses that resulted from a mixture of viruses from different host species to form a unique variant, different from either parent virus.

Nodding disease is one of those that has only recently appeared on the radar of those of us in public health, although it is not truly a “new” disease. It was first described 40 years ago, but this syndrome has been sufficiently rare as to not merit significant medical attention until 2010. Outbreaks of nodding disease have now occurred in South Sudan, Tanzania, and Uganda, affecting thousands of children. The disease first presents as cognitive difficulties; then the nodding starts, especially when children are provided food. They experience further cognitive decline, and ultimately regress to an almost infantile stage, where parents cannot leave them unattended for fear they may wander off or injure themselves by accident. Death appears to often be a result of such accidents: (drowning, falling into a cookfire) or starvation, as the seizures in the late stages of the disease seem to make it virtually impossible for the child to eat. No one is known to have recovered from the disease.

While the cause(s) still remain mysterious, studies have been done trying to determine risk factors for disease development. A recent CDC-assisted study, for example, was carried out in the new country of South Sudan. This examined 38 matched cases and controls and examined dietary as well as infectious disease factors, looking at issues such as vitamin deficiencies, a history of hunger, and current infection with the parasite Onchocerca volvulus.

This particular agent is interesting, as the nematode already causes a well-known disease, river blindness. Like many parasites, the life cycle of O. volvulus is fascinating and complicated. Humans are the main host, who are initially infected via the bite of the black fly, which was herself infected with O. volvulus from a previous human meal. After inoculation, the nematode larvae migrate to the subcutaneous tissue of their human host, where they multiply and mature over the course of 6-12 months, eventually mating and producing microfilariae–little baby worms, up to 3000 per day per female nematode. It’s this life stage that are then ingested by black flies during a daytime meal, when the microfilariae migrate to the host’s skin. Within the fly, they will mature through three larval stages, ready to infect another human host.

How then do these worms cause blindness, if they live mainly in the subcutaneous tissues and, sporadically, the skin? The microfilariae also migrate to the surface of the cornea, and when these organisms die, they cause an intense immune response. Interestingly, this response seems to be due not to the worms themselves, but to their Wolbachia symbionts–bacteria species notorious for infecting parasites (and insects) and causing all sorts of weird things to happen. Repeated episodes of this inflammation can lead to keratitis, and the cornea eventually becomes opaque. O. volvulus can also cause intense skin itching, leaving dead and discolored patches of skin in addition to the characteristic blindness. In all, it’s a nasty disease but one that is relatively simple to treat if caught early, either with antiparasitic drugs or even with antibiotics such as tetracycline to kill the Wolbachia. The disease can also be prevented by fly mitigation and preventative doses of anti-parasitic medicines.

Testing for O. volvulus is relatively simple. The MMWR study used a “skin snip”–just as it sounds, taking a small piece of skin from the patient and examining it for microfilariae. However, this has the limitation that it may miss early infections (where microfilariae have not yet developed and spread) or mild infections (where there are fewer organisms per square millimeter of skin sample). They note that they also took blood samples to examine antibody responses, but those data were not yet available.

What they found was interesting. In one village, Maridi, they found a matched odds ratio of 9.3 (with the cases being more likely to be currently infected with O. volvulus than the controls), which agrees with an earlier study done in Tanzania which found high levels of infections in cases. However, no healthy controls were tested for comparison in that publication. Furthermore, in the South Sudan study, no statistically significant difference in parasite infection was found between cases and controls in the second village, Witto. Why the dramatic difference between the two locations in the same country? Don’t know. It could simply be related to small sizes (only 25 pairs were examined in Maridi, a “semi-urban” area, and 13 in Witto, described as rural). We also don’t know anything about temporality–were the patients affected before they developed nodding disease, or subsequent to the start of symptoms? Even though many questions remain, the Ugandan government is taking steps that look as if they believe a cause of nodding disease has been found, and that O. volvulus is that cause. While additional measures to stop the spread of the parasite are probably a good idea in any case (reducing river blindness is also good), I certainly wouldn’t call this case closed, and neither did the individuals speaking on this issue recently at ICEID, where this outbreak was discussed in at least two sessions I attended.

There is biologic plausibility for O. volvulus to cause a seizure disorder. Several other types of parasites can cause epileptic conditions, including the tapeworm Taenia solium, which can originate in beef or pork products. Could it be that O. volvulus is getting into the brain and causing pathology, leading to seizures? The 2008 Tanzanian study suggests no, as the cerebral spinal fluid was tested in 42 patients and found to be negative for O. volvulus DNA in all patients.

With some emerging diseases, there is the risk that the incidence of a disease is increasing due only to awareness of an illness–the more doctors that recognize it, the more cases they will diagnose. However, there is anecdotal evidence that this isn’t the case with nodding disease:

Dr. Abubakar said in an interview that while the syndrome is known to have existed for some time in South Sudan, the recent spike in reported cases could only partially be explained by wider awareness and better surveillance. “It’s not only local authorities but local NGOs saying more children have been affected,” he said. Particularly striking, he said, is that in South Sudan “there are a number of displaced people from another location who did not have nodding. But after the displacement, when they moved to affected areas, after 2 years the children started developing the syndrome.”

Additional studies and more thorough surveillance are needed to confirm that this is true, which would suggest a localized focus of disease in multiple different areas (which does seem to be the case at this point in time).

The migration aspect is intriguing, suggesting some sort of environmental exposure–if it was simple genetics, where the children were living shouldn’t matter. However, this puts us back almost as square one, examining what is present in the local environment–both infectious and non-infectious agents including heavy metals and various toxins.

The work investigating nodding disease is still in its infancy, but already “nodding disease” has affected more individuals than all of the recorded cases of Ebola. Now that there is recognition of the disease, and some international support for research into its causes, hopefully better treatment and prevention efforts will follow.

Works cited

WInkler et al, 2008. The head nodding syndrome–clinical classification and possible causes. Epilepsia. 49(12):2008-15. Link.

CDC. 2012. Nodding Syndrome — South Sudan, 2011. MMWR. 61(03);52-54. Link.

Castrating sheep with teeth: not a good idea (with video!)

Just a quick post as I’m in end-of-semester hell. Via Maryn McKenna on Twitter, the CDC has released a report of Campylobacter illnesses due to not food consumption, but because of castrating lambs. With their teeth.

On June 29, 2011, the Wyoming Department of Health was notified of two laboratory-confirmed cases of Campylobacter jejuni enteritis among persons working at a local sheep ranch. During June, two men had reported onset of symptoms compatible with campylobacteriosis. Both patients had diarrhea, and one also had abdominal cramps, fever, nausea, and vomiting. One patient was hospitalized for 1 day. Both patients recovered without sequelae.

During June, both patients had participated in a multiday event to castrate and dock tails of 1,600 lambs. Both men reported having used their teeth to castrate some of the lambs.

Among the 12 persons who participated in the event, the patients are the only two known to have used their teeth to castrate lambs.

Sadly, this wasn’t the first time I’ve heard of such a procedure. This was on Dirty Jobs a few years back (and yes, Mike Rowe participated–not for the squeamish).

On a related note, my grandma always had sheep on her farm. I helped to shear but never castrate. Now I’ll have to ask my dad and uncles what method they used…

Hemolytic uremic syndrome (HUS) in history–part 1

It appears that the E. coli O104 sproutbreak is starting to wind down, with more than 3,500 cases diagnosed to date and 39 deaths. Though sprouts remain the key source of the bacterium, a recent report also documents that human carriers helped to spread the organism (via H5N1 blog). In this case, it was a food service employee working at a catering company, who spread infection to at least 20 people before she even realized she was infected.

As with many infectious diseases, there are potential lingering sequelae of infection, which can occur weeks to years after the acute infection has cleared up. Like almost 800 others involved in this outbreak, the woman who unwittingly infected others via food developed hemolytic uremic syndrome, or HUS. We now know that the most common cause of HUS are bacteria such as STEC (“shiga toxin-producing E. coli“); the “shiga toxin” that they produce inhibits protein synthesis in the host and cause cell death. This can have systemic effects, and leads to clotting in affected organs–most commonly the kidneys, but other organs can also be affected. Dialysis may be necessary, and the infection can lead to kidney failure and the need for organ transplantation. There is already concern that, because of the huge numbers of HUS cases, many patients will have long-term kidney damage, including the potential need for additional organs (and possibly, re-vamping the way donations are made as well):

In previous E. coli outbreaks, up to half of patients who developed the kidney complication were still suffering from long-term side effects 10 to 20 years after first falling sick, including high blood pressure caused by dialysis.

In addition to possible kidney problems, people who have survived serious E. coli infections may also suffer from neurological damage, as the bacteria may have eaten away at blood vessels in the brain. That could mean suffering from seizures or epilepsy years after patients recover from their initial illness.

While it’s common knowledge in the medical community now that STEC can lead to HUS, which can lead to chronic kidney issues, for many years, the link between E. coli and HUS was obscured. HUS first appears in the literature in 1955, but the link to STEC wasn’t confirmed until the early 1980’s. In the interim, myriad viruses and bacteria were examined, as well as genetic causes. (There are cases of HUS caused by host mutations and other etiologies, but they are much less common than HUS caused by STEC and related organisms). In future posts this week, I’ll delve into the history of HUS and look at a few studies which examined alternative hypotheses of causation, until finally STEC was confirmed as the causative agent. I’ll also discuss what this means as far as discovering infectious causes of other “complex” and somewhat mysterious diseases whose causes are unknown, as HUS was a mere 30 years ago.

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.