Ep 114 Listeria: It put dairy on the map

ulcerations at all. This is important. A little later in August, she started having some excruciating headaches after she would eat, and when she saw her doctor, they diagnosed her with a condition called temporal arteritis and started her on high dose steroids and methotrex eight. At the same time, she had a long standing trip planned August eighteenth through October ninth to go up to Washington to visit some friends and escape the heat of the Palm Springs desert. I'm

a nurse. I've been a nurse for twenty seven years. I talked to her about the risks of continuing to go on this vacation because of the immunosuppression that the steroids were causing, and I think because of the COVID fatigue for the past several years and not seeing her friends. She wasn't really interested in putting that off. She had people to see, things to do, and golf to play, and away she went fast forward up until September twenty fourth.

She texted me that she had gained two pounds, She'd eaten a great big bowl of ice cream, and was having some macaroni and cheese for dinner. On the twenty eighth, she called because she said that she had started not feeling so good. So then the next day was Thursday, the twenty ninth, she called me in the morning and said that she was feeling worse, and she did go ahead and cancel her lunch date that day. So Friday, September thirtieth, I received a call at three o'clock in

the afternoon from the people she was staying with. She'd been laying on the couch all day, had not eaten any food and only taken SIPs of water, had a low grade temp, negative COVID tests, and because I'm down here outside of Palm Springs, I said it was a good idea to take her to Virgin Care. So they did take her in. The blood work came back and showed that she had some impaired kidney function, borderlining on kidney failure. She also had a really high calcium level

and a low potassium level. The doctor there, though, thought that she was stable enough that she could just come back in the morning and get some ivy fluids and repeat the labs the morning of October first, they went to the urgent Care straight away, where she got her fluids. The doctor did advise our friends to go ahead and

take her over to the emergency department. She was checked in entriaged about three and then because of just how life in the er is these days, she got back to a room at like eight thirty at night, and the doctor saw her at ten o'clock at night. Luckily, our friends were able to stay. They rotated staying with her so that she wasn't just by herself, and at three point thirty in the morning, she had a sudden mental status change where she completely went lethargic, started reaching

at the air, not communicative, not able to speak. So our friend Frank grabbed the nurse. They took her temperature rectally and it was one hundred and three point four. The staff came and drew blood cultures and she was started on an ivy antibiotic cocktail that they do for sepsis of unknown origin. I got on the plane to go up to Portland at like nine o'clock in the morning on Sunday. I arrived at the hospital at eleven am. She looked like she was going to die when I

walked into the room. I worked eleven years in the emergency room, and I thought, oh, this is not good. It's not good at all. She was not responsive to people talking to her, she was not following commands, she was pulling at things. On Monday, the third, the infectious disease doctor came to me about noon and said that three of the four blood culture bottles were showing bacterial growth of some sort, but that the microbiology text that

he knew and really trusted didn't I identify anything. So he was really concerned that it was contaminant, which would be really highly unusual in three out of four bottles. So they ran what they call an extended infectious disease panel.

After she came back from her lumbar puncture, the infectious disease doctor comes down the hall towards me and kind of frantically gesturing at me and says, you're not going to believe this, but she's actually got listeria and it's her blood stream and it's also in her spinal fluid,

and this is really really bad. And it's bad not just because, I mean, the mortality rate is exceptionally high, but also because the antibiotics that she had been getting are not the ones that are effective at all against lysteria. It took until eleven o'clock at night to finally get her started on the ampicillin. But I was still preparing myself that my mom was going to pass. So when I came in at six point thirty Monday morning, my mom had little restraint mittens on her hands, and I thought,

oh my god, it's gone from bad to worse. And she was shaking those little mittens at me, and I said, Mom, if I take these off of you, you have to leave your things alone. You can't pull on things. And she made eye contact with me and she said okay, and I thought, oh my god, she's in there. This is a glimmer of hope. I think it could be. It could be okay, And over the course of the day, her mental status actually improved. She was answering yes and

no questions. I was able to transfer her out of bed and get her on the little bedside commode to go to the bathroom. We also discovered at that time in her MRI that they had done of her brain that it showed that she had four areas that were possibly like septic ambolai from the infection. So to see her mental status also improving like that was really amazing. They had given her a medication called Erykstra to prevent blood clots, and they also gave her an aspirin because

of the potential for cardiac strain. So I was a little worried about that when they started that the day before because of her platelet account was not super low, but it was low enough that I was concerned about it. So Wednesday morning, when she's talking and moving and she's doing great, she told me that she had just never felt so awful. And I explained to her that most people that get as sick as she is, don't even

wake up. And she looked at me. She said, you mean I could have died And I said, yes, mom, it's that serious. You could have died. And she said, well, I'm not ready to die. And I said, well, that's great, because I'm not ready to be an orphan. Everybody was so excited, her doctor's, the hospitalist, and the infectious disease doctor. They were just amazed at how good she was doing. And then at three point thirty I got her up to the commode. As soon as she went to the bathroom,

I knew right away that there was blood. When somebody has an intestinal bleed, it has in a past tool it has a very very distinctive smell, and I just knew that this was not good. And that was really the very beginning of the end. The doctor came back up and looked at it and he said, yeah, we're going to hold off on transferring her off the floor. So they did an upper endoscopy where they looked at her stomach on the seventh and that was negative, no ulcers.

So they did do the colonoscopy and that showed that her large intestine and all throughout her large intestine and up into what they could see in her small intestine was just riddled with ulcers. On the fourteenth, she really started bleeding quite heavily and went into shock. And before she actually went into full blown shock from this, I had to call my daughter and tell her that if this scan that they had just taken her for did not show any bleeding that we could do anything about that,

her grandma was most likely going to pass away. That was the hardest phone call I've ever had to make. The results of that scan came back and they finally did see that there was bleeding coming out of an artery in her small intestine, so interventional radiology was called in and off she went for procedure and off to ICU. That procedure we thought was good, but then in the morning it turned out that they had maybe stopped the bleeding a little too well and some of her small

intestine was starting to die. So this led down the course of a bowel resection and then reattachment, which she did great came out of that very well. By the twenty sixth she had had twelve units of blood, two failed interventional radiology procedures, and three surgeries. Throughout this time, with her in Washington with when the bleeding would stop

and it would start. Our only goal was to get her home, to get her back to California, and trying to navigate that when you're at a hospital system that so eleven hundred miles from your home is exceptionally difficult. But throughout the whole time that was our single focus, get her home so that she could pass at her home when it became obvious that she was not probably going to pull through this, and thankfully we were able

to do that. On the second of November, I was finally able to get her on an air ambulance home to get her admitted down here at the hospital system that I work in. I was able to have hospice come out bring the bed and all of the equipment here on the fourth and my dear, dear friend Julie was with her at the hospital in the morning and she called me and she said she's ready. She was alert, and she knew she was in the hospital and she

was ready to come home. She has a beautiful view at her condo here and.

beautiful and she's missed every day. And thank you for letting me share her story.

be very bad. But I just sort of had lumped it all in together with some of the other culprits and I had no idea.

solutions like high salt to preserve foods, et cetera. And then on top of that, you have this biofilm formation which can form on food production equipment and be really difficult to get rid of.

inhabitant of both animal and human guts. And so there's a lot of evidence that we are all probably exposed to Listeria monocytogenies on a relatively regular basis, and it's a really common pathogen in the environment because of this.

have some diarrhea or some nausea vomiting. If that's the case, then those symptoms would generally start within about twenty four hours of exposure and last for about one to three days, which is a really common time frame, and set of symptoms for a food born gastroenteritis, but we have essentially no clue how often this happens or what's the likelihood that if you're exposed to contaminated food that you get this kind of infection in the absence of any other

risk factors for invasive affection, which we'll get to because we just don't have data on it. Most of the people that are getting food borne illness of any kind, we're never detecting what that pathogen actually is, and they.

and then this leads to an invasive infection. But that is often not the case when it comes to listeriosis. So while we can see this gaster enteritis, nausea, vomiting, diarrhea, maybe fever, you're feeling crappy, but the cases that we worry about are actually separate entire and the incubation period for these is not twenty four hours. It's one to four weeks or more. Whoa, yeah, So it's separated in time entirely. And so that's why I say, was there

a preceding diarrhea? Maybe would we even remember it? Maybe not? But most of the data that I see doesn't even mention whether or not there was a preceding gast or enteritis.

is not necessarily a usual suspect. Now that aaron one to four weeks, so is there like a threshold response where it's like the bacteria you know, replicate in high enough numbers, that's suddenly they're systemic Because it seems very sudden. Yeah, let's talk about it, Okay, getting like very excited, like not excited, but like intense about this, and I can dial it back. No, I love it.

and the CNS, the nervous system infections. We'll talk about what those look like, how they present, how somebody would show that they have this infection, and what the results tend to be, which are spoilers not good, And then we'll talk about the path of physiology that kind of unites them about this bacteria. So when it comes to perinatal or neonatal infections, overall, on average, they account for an estimated ten percent plus or minus of all listeriosis cases.

And again, when I say listeriosis, I just mean these three invasive infections. Think of the food borne illness as totally separate. Oh okay, m But perinatal infections are a huge cause of morbidity and mortality, especially of neonates. So I'm going to talk about that first. So, a perinatal infection means infection with listeria during pregnancy, and the symptoms here tend to be very non specific. It's often what's called a flu like illness. So fever, chills, malaise, muscle aches,

your overall feeling really crappy. Some of the papers that I read described it as sometimes being mistaken for pylo nephritis, which is infection of the kidneys.

depending on how far along you are in pregnancy. It can lead to premature labor and delivery, which can have a whole host of complications arising from that prematurity, and it can also lead to a both an early neonatal infection right when that baby is born, they can become infected and have signs of either sepsis or meningite, or if infection happens around the time of delivery, it can

lead to a late onset meningitis. So a few days or weeks after delivery, the baby can end up super sick from listeriosis as well.

point we see severe complications for the fetus. Okay, so it's always super high risk, always super high risk, yeah, which is terrifying. Yeah, and again here we tend to see a delay of one to four weeks between exposure for the pregnant person and when they start to have these symptoms of fever chills, that mean that they have listeriosis and now the fetus is also infected.

have listeriosis during pregnancy. They're feeling really sick, so it's very likely that they may go in and seek care and you would see that they have signs of an infection. But it's generally not life threatening for the pregnant person, right, Okay, that's the big difference. Yeah, it is, though life threatening for adults who are not pregnant. In the other cases

that we'll talk about. So let's get to that, shall we h. And by the way, when I'm talking about groups who are at highest risk for infection aside from during pregnancy, there are a few groups that we see that are at highest risk. Primarily it's those of older age, especially over age sixty five, whether or not they have any immunal compromising conditions, but especially if they do have things like diabetes or perhaps we're on steroids for one

reason or another. So older age is the primary risk factor. We also see it like with neonatal infections in the very very young, as well as in people who are immunal compromised for one reason or another, which includes poorly controlled HIV infection or progression to AIDS, which we actually see as a really big risk factor for listeriosis. So what are these other infections look like outside of pregnancy.

So in the case of a bloodstream infection with listeria, which by the way, accounts for anywhere from thirty to fifty percent of cases of listeriosis, which is a.

like you're just not feeling like yourself. You often have chills, and because this is a cause of sepsis, then it's going to go on to develop the same severe complications and outcomes that we see in sepsis from any other bacterial organism, that is, multi organ failure and eventually death

from an overwhelming bacterial load in the bloodstream. But what's interesting is that there often isn't like a single presenting organ that you might suspect as the ideology of this infection, because while you got infected through your guts several weeks prior to presenting with these symptoms of bacterymia or septicemia,

you may not have ever even had gastroenteritis symptoms. So in that way, it's different than when we talked about sepsis and you're trying to think of like what is the source, This would probably be a case where you'd have a really hard time identifying what is the source of this infection. Yeah, and when it comes to bacteremia and septicemia, the mortality rate is twenty to thirty percent, and that is even with treatment.

confusion or even disruption in consciousness. Usually the onset is a little bit less abrupt than some other more common causes of bacterial meningitis like numacoccle or meninchoccle meningitis. And it's often harder to detect listeria in for example, a spinal tap, because this is an intracellular bacterium, so you have to wait until cell culture results because it's not

gonna show up on a gram stain necessarily. Okay, But one thing that's also interesting and seems to happen with listeria, and I don't know the frequency because some papers were like, this isn't specific to listeria, and some were like, yes it is. But it's a specific and bizarre form of meningitis that infects the cerebellum, the back part of our brain, like the and you look at a picture of a brain it's like the two tiny balls on the back,

and this is a romb encephalitis. You see similar signs as a typical encephalitis fever, headache, but more often you'll also see a lot of nausea and vomiting, and then signs of what we call cerebellar dysfunction, like not being able to walk in a straight line, what we call

a taxia. You might see cranial nerve abnormalities because you're cranial nerves that innervate the muscles and sensory system of your face and neck come out in our brain stem near the cerebellum, and so you might see various palsies or abnormalities in the function of those nerves. And this is what we see in animals, especially ruminants who get

infected with listeria. This exact same type of infection a romb encephalitis, and it can lead to very odd behaviors, including circling, where animals walk in unidirectional circle and they have like head and neck deviation to one side. And it's all because of this infection in the back part of the brain and the brainstem.

use to keep pathogens out. First, it's crossing over our intestinal epithelium, so it's no longer just limited to our guts. It has a really easy time penetrating these tight barriers. It makes its way into our lymph system and our blood stream, where It can then travel to our liver and our spleen and in theory any organ but primarily the liver and spleen, and continue to grow and progress

to infection. It can then also, like you said, aaron, cross our blood brain barrier, so it can cross through these other really tight cell to cell junctions made to keep bacteria out, and then it very easily crosses the placental barrier and is able to infect a developing fetus. So how is it able to do this? How is it so easily able to cross these barriers? The truth is that it's largely because this bacterium has adapted to not just survive, but also divide, continue replicating, and thrive

within the sidasol of our cells. Both cells like our macrophages, which which I talk about a lot, but these are the white blood cells whose job it is to go out and find and engulf and usually neutralize bacteria. So Listeria can survive that normal neutralization process that macrophasias do by actually hijacking those macrophasia's machinery and breaking out of the vacuoles that we've trapped it in and replicate inside of those macrophases. But Listeria can go one step further.

They can then actually escape sell to sell.

that part. They can intentionally travel from cell to cell to sell without having to burst out and enter our bloodstreams or our lymphatics. And they can do this not just in our macrophases, our macrophases and other white blood cells, intentionally in gulf bacteria. So bacteria have an easy time getting inside of macrophasis. There's a lot of bacteria we've talked about on this podcast that can survive inside of macrophage. They've evolved to escape that one protective response. But Listeria

take it one step further. They have a whole host of other receptors that allow for them to intentionally enter our other cells like our intestinal epithelium like other cells in our spleen and our liver and throughout our body and survive and replicate within those cells as well. It's it's incredible.

that overwhelming infection that now we're really sick from. I don't know which of those two my suspicion is that it is the latter, where in people who don't have any risk factors, who are not getting severely ill from this most of the time, this bacterium is not establishing an infection in our cells for a very long period of time.

you actually see listeriosis manifest itself. And that is largely because of the way that it's an intracellular only pathogen. Our T cells are much more involved in that part of our immune response, like killing infected cells versus antibody responding to bacteria that are free floating in our bloodstream. Okay, So you don't see a lot of the more antibody mediated response with.

It involves the discovery of a new pathogenic microbe in the early twentieth century, and then it's followed by the realization that, hey, this pathogen is a lot more widespread than we previously thought, and then people tracing its spread not just in present day but also in the past. And it's a fascinating story of discovery, and it follows this common pattern. But what I think separates the story of Listeria from these other ones comes down to a

few things. And by the way, when I say listeria, I am specific referring for the most part, unless I say otherwise to Listeria monocytogenies, I mean same. Yeah. But one of these things that separates this story out from some of the others is what I found to be a surprising delay between discovery and when people realized how it was commonly transmitted. And we'll get into that. And the other is just how well we can see the

drivers of pathogen movement across time and space. Oh okay, and that's not just in hypothetical terms, but by looking at what this bacterium's biology can tell us about the past. It's I love this ooh okay. We'll get into all of it, but first let's start at the beginning. And I'm skipping right to the discovery side of things, because even though you asked where did this thing come from?

Listeria is widely distributed in the environment, and it can infect a ton of different animals, and so I don't really know when or where it first emerged. There are some papers looking at the evolutionary relationships among some of the species within the Lasteria genus and some of the nonpathogenic ones compared to the pathogenic ones, and looking at when did they evolve virulence and so on and so forth. But I'm not going to get into it. Okay, okay,

but when did we as humans first recognize it as such? Well, sometimes people look for a pathogen to match a known or an infamous disease, think like plague or cholera or something. Other times it's more of like a fishing expedition. You cast your net and you see what you pull up. There are some where people are just like, let's collect swabs from infants' throats and see what we find, or from pond water or this rabbit's foot or something.

and I love when that happens with older papers. Like it was lovely. So I have a lot of quotations here from it, hopefully not too many, but I think you'll enjoy it. I love it already, all right, prepare yourself. This is a long quote, okay quote. An important responsibility attached to the breeding of normal laboratory animals for the Department of Pathology was the routine autopsies on animals which died.

This practice was rewarded by the control it exercised over the quality of the stock and by the interesting diseases it discovered. Foremost amongst these is the disease described in this paper. In May nineteen twenty four, six cases of rather sudden death in rabbits were observed to present strikingly similar lesions, though no direct cause of the evidently acute, toxic or infectious condition could be discovered in any of them.

The interesting characters presented by the disease and the increasing mortality amongst our young rabbits caused us to watch carefully for any signs of illness and to investigate all cases which occurred. Although there seemed to be every reason to say suppose that the disease was of a septocemic nature, all cultures from the heart's blood remained sterile. During July nineteen twenty four, small gram positive basilla were found in films of the acidic fluid in a guinea pig and

in smears from the omentum of a rabbit. Side note, I don't know what an omentum is, so I did look it up. I forgot to do. You want me to tell you? Yeah, yeah, I tell you.

began and quote. So basically what happened here was that they found this disease, they found some sort of condition in these rabbits. They kept culturing and culturing, and then

eventually they found this gram positive basilla. And after that point, once they were able to culture this, they conducted a bunch of observational and experimental work which included a combination of clinical observations of the young rabbits in the lab, autopsies, tissue preparations, experimental infection, culturing the organism, things that are not just the usual but like the usual, and then some This was a packed paper full of information. It

was really quite impressive. What they found was that the infection seemed to hit the young rabbits particularly badly, causing some to die very suddenly and others to die over the course of weeks. The researchers remarked on how striking the disease was, like how distinguishable it was once you saw it in an animal. There was very little else that they felt it could be I thought was really interesting because we've talked about in the biology section, Like

you talked about it's very difficult. You can't look at someone and go, oh, that's listeria for sure, right, but they evidently could do that, at least in the way it manifested in rabbits. And it was this characteristic nature of the disease that was part of the reason why Murray, the lead author on the paper, thought that this must

be a new pathogen not yet described. Quote. Both the natural and experimental disease have interesting and characteristic features, and their consideration has forced us to the conclusion that the causative organism either has not been described previously or has been inadequately described, and so cannot be traced in the literature. In either case, we feel justified in naming it. Its salient character is the production of a large mononuclear leucocytosis.

This is by far the most important and most striking character we have discovered, and we name the microorganism we shall describe in this paper Bacterium monocytogenes. I love that. I love it. We feel what was it? We feel justified in naming it. I love it. I mean they maybe they were justified in naming it, but they certainly weren't the first people to culture it, especially given its widespread prevalence in nature.

as something else. But then also, retrospective analysis of old tissue sections seemed to indicate that people there were human infections at least before World War One. Okay, I mean all of this is just to say that, like, this

bacterium has been around. There was no sudden rise necessarily or any sort of reason why Murray was in the right time and place for it was just a really well written paper, But unlike we've seen with other infectious diseases in the past, it didn't necessarily lead to this widespread recognition where everyone's like, oh my gosh, I see it. It's everywhere. Suddenly, here's Bacterium monocytogenies. It kind of laid

low for a while. It was mentioned in textbooks. It got a genus name change along the way from Bacterium or whatever it was called to Listeria. And also side note Listeria, of course, is to honor Joseph Lister. Mister features in our Percepsist episode, so go check that episode out if you want to learn more about his story

if you haven't already. Anyway, in the twenty five years or so since Murray first cultured this bacterium, it didn't really make itself known as a pathogen of public health importance. Took a while, which I find interesting. Mostly it was found in small rodents or in domestic animals like sheep,

causing occasional outbreaks in those organisms. There were a handful of human cases reported in Denmark in nineteen twenty nine, and at the time it was thought to be related to infectious mononucleosis, but in general it was thought to be extremely rare in humans, so rare that it didn't merit a mention in bacteriology textbooks relevant to human health

at the time. Wow, But it did merit a note from a researcher named Burns in nineteen thirty five who warned that Listeria monocytogenies could be a cause of granulomatis

septicemia in infants and fatal meningitis in adults. But this warning by Burns was either forgotten about or never heard in the first place until nineteen fifty one when HPR Seliger at the University of Bonn, who wrote the textbook on Listeria literally and I think there's a species named after this researcher as well, when Seliger isolated the bacteria from lesions in newborns who had infections that resembled some that had just been written about from Germany had just

been published about, and so researchers there in Germany a couple of years before had isolated the same bacteria from various tissues of eighty three newborns and stillborn infants who had been diagnosed with quote unquote Granulomatis in fantaseptica, which

was thought to be a never before described infection. Oh okay, but these researchers thought that the bacteria they had found was a kind of Krina bacterium, And it was only realized that it was Listeria monocytogenies after Seliger recognized it as such a couple of years later. So, like I said, this was certainly not the first time that Listeria had

infected humans. And some researchers have looked back at case reports from the late eighteen hundreds and early nineteen hundreds and hypothesized that listeriosis may have previously been diagnosed or described as quote unquote pseudo tuberculosis or quote unquote neonatal septicemia.

And I saw a reference to a paper that I couldn't access where the author speculates that Queen Anne, who lived from sixteen sixty five to seventeen fourteen, had repeated pregnancy losses, still births, neonatal deaths, and post natal meningitis seventeen pregnancies overall with no living offspring. Oh, and some people have speculated that it was due to listeria. I don't know. That's a lot of lasteria, it's a lot

of lysteria. So even though we know that listeria probably infected people throughout history, there's no way to make precise estimates of past prevalence for something like listeriosis. But infections did seem to start rising in the second half of

the twentieth century. This could be due in part to the increase in microbiology techniques and the fact that people knew about listeriosis, but or I think it could be the large scale changes in food production and the lag in food safety policies that had been taking place and continued to take place throughout the twentieth century. Yeah uh huh.

primarily associated with food. Many outbreaks have been traced to food like milk, cheese made with raw milk, deli meats, hot dogs, fruits and veggies contaminated with manure containing listeria, but the link between listeria and contaminated foods was only made in nineteen eighty three after an outbreak of listeriosis among pregnant people and infants, with an extremely high mortality rate of twenty seven percent of the infants born alive

despite aggressive supportive care and forty seven percent overall nineteen eighty three nineteen eighty three. So this particular outbreak was linked to coalslaw that had been contaminated by sheep manure containing listeria. So before then, before this this outbreak, researchers suspected that humans got infected with listeria from some kind of indirect transmission from animal sources, especially given its widespread prevalence in domestic and wild animals, but this was the

first time that it was actually demonstrated. Epidemiologists went to the farms or went to the food production facilities where this coal slaw had been processed, and they were like, oh, it's in the everything, yeah, yeah, And later on I'm going to pick back up on some of these food born outbreaks of listeria and lessons learned and so on, But first I want to head back into the Industrial

Revolution where I started this whole like topic. So, during this time, as more and more people began to move to live and work in cities, food production had to change to accommodate these increasing population densities. There was more of a demand for mass produced foods and process foods as the time from harvest to table grew longer and longer.

And of course, as we've talked about on the podcast, before food safeties or technology allowing for analysis of food and food safety, it lagged tremendously far behind these new food production practices, especially in the US, where the giants and food industry, who were more concerned with profit than the health of their consumers actively discouraged any safety legislation from being passed in the US for years, years, decades. Person surprised, Oh, oh, it's even though it's not surprising,

its shocking somehow, still just appalling. Maybe milk was diluted with pond water, it was preserved with formaldehyde and adulterated with plaster of Paris to get rid of the murky blue tint because it had been diluted with like pond water, and you could see horse hair worms swimming in and of it and stop it. But the plaster of Paris made it look farm fresh and straight from the utter. Stop it.

If you want to learn more about this, stay tuned to the podcast for a bonus episode later this season where I interview Deborah Blum about her fantastic book The Poison Squad, which goes into the fascinating history of food safety in the US. Oh, will read the book now if you don't feel like waiting for the upper Yeah,

it's such a jaw dropping book. Oh my gosh, that's yeah. Okay. Anyway, it's easy to see how these practices with essentially no oversight for food safety, mass processing of milk based products and meats, longer times between production and purchase, no refrigeration. How these things would have led to a massive increase in listeria, both in terms of prevalence as well as geographically. But this time we don't have to settle for speculation.

A paper from twenty twenty one by Maura at All traced the global spread of listeria, particularly one clonal group LMCC one, if anyone's interested, and this clonal group commonly causes infection in humans and is often found in cattle and dairy products, if you remember from our Anthrax episode. The clonal aspect of this really helps with being able to more closely trace diversification and rates of evolution and

so on. And when these researchers looked at the genetic diversity of this group, what they found was that around the mid nineteenth century Industrial Revolution time, this group, this clonal group, underwent a big period of expansion both in overall diversity as well as geographic expansion, particularly in Europe.

If you overlay this with what was going on in the global food trade, you would find that in eighteen seventy the North Atlantic Meat Trade Agreement was passed, which allowed for excess cattle in North America to be shipped to Europe, whose cattle population had dwindled due to things like contagious bovine plural pneumonia and foot in mouth disease. It's all about diseases, like I always everything.

to Europe. Wow. And right around this time, the researchers estimate, is when this particular clonal group of listeria arrived in Europe, after which it spread across the continent, helped along by railroad expansion which was currently going on both in Europe and North America, and it continued to diversify along the way.

A drought in Oceania from eighteen ninety five to nineteen oh three led to cattle and their listeria being transported there, and then subsequent decades saw the continued global spread of this pathogen from North America to Asia to Oceania, from Europe to Africa, basically all over the world, and the pattern in genetic diversity of Listeria supports this increasing during

this time of widespread cattle movement. And then this is the part I find so interesting, slowing down during the Great Depression, when countries such as the US and many other countries stopped exporting cattle and other foods for a while, so we're like, we need to food our people in this variety or whatever.

like E. Cola one five, seven, seven. Sooo, it seems pretty likely to me that the apparent rise in Listeriosis around the mid twentieth century may not have been just because people knew what to look for. Seems like it could be tied to the widespread global expansion of this pathogen.

these safety measures. Oh my gosh, how interesting. It is so cool And I really hope that I interpreted this paper correctly. And granted, this study did look at just one clonal group, and there are others that are known to cause disease in humans. But I think it's just so cool because usually on the podcast, I feel like I'm talking about the spread of this or that pathogen

in purely hypothetical terms. It's likely that this period of history led to the proliferation of this pathogen because more people were going to hospitals or as we know, war always leads to increased infectious disease because of crowded and unsanitary conditions, Like it's not very often that we can actually trace the impact that certain political practices I think had on a disease that we know about so much more recently than I don't know. I just think it's so cool.

of infection, like whether it be from a particular herd, maybe there's a really high prevalence and a certain herd on a farm or within a certain farm, or within a certain processing facility, and that's where public health officials can sort of target or put resources to eliminate the

bacterium there. And on that front, We've made a lot of progress since the nineteen eighties, in large part thanks to the outbreaks of listeriosis that highlighted just how deadly it could be, sparking these public health and food safety responses. So earlier I mentioned that nineteen eighty three listeria outbreak in Canada tied to contaminated coalslaw and that was the one that really solidified food as a source of the pathogen. But that was really only the beginning in terms of

food associated outbreaks of listeria. That same year, another outbreak of listeriosis involving forty nine people, primarily infants and aminosuppressed adults, and a fatality rate of twenty nine percent was detected in Massachusetts, this time linked to milk, not raw milk, but pasteurized milk, which pointed towards dairy products as a source of listeria minus cytogenies, because remember the first one was Coleslaw, and so this one really put dairy on

the map. And sure enough, a couple of years later, soft cheese was the culprit, and a large outbreak of listeriosis in California involving at least one hundred and one human cases and fifty or more deaths.

And one consequence of these outbreaks was that screening for listeria, especially in cheeses and other dairy products, ramped up significantly all over the world with the finding that listeria was so so much more prevalent in certain types of cheeses as well as in raw meat and meat products than

anyone had guessed before. And of course, with this alarming news, at WHO and national public health authorities got involved and began to investigate how to best stop this bacterium from getting into the food supply, and how to raise awareness among medical professionals about potential outbreaks, and how to estimate or even begin to estimate the scope of this problem.

Research into the ecology of this pathogen revealed how widespread it was, not just in livestock settings, but also in the wild, found in soil or infecting wild animals like I read one paper that found Listeria monocytogenies in nearly half of the black bears that they sampled in parts of the eastern US bears. Oh my god, I know.

And also how different conditions in farms, things like herd size or livestock composition, like whether you have this many sheep or this many cattle, or whatever, grazing or housing practices, how all of these things could change the amplification or dispersal of the pathogen or select for certain strains that differ in their abilities to infect humans or livestock. Basically, there's been a lot of information that we have uncovered

and are continuing to uncover. And while outbreaks did continue to happen and continue to happen today, these improved safety measures, along with this greater understanding of the ecology of this bacterium, led to a pretty substantial decrease and reported the stereosis cases in the nineteen nineties from eleven per million population in nineteen eighty eight to four cases per million in nineteen ninety eight. So it's like, that's a pretty substantial decline.

In nineteen ninety nine, a US wide outbreak involving one hundred and one cases and twenty one deaths linked to hot dogs stopped lysteria from dropping further down on the food borne priority list as it kind of had been doing since. Like, Hey, the measures we're implementing are working, and this outbreak, in conjunction with other sporadic outbreaks as well as individual cases, has kept people searching for ways to stop this pathogen from invading the food supply chain.

And I have to admit that when reading about all of these outbreaks and the subsequent response, like it's great that there seems to be a response, but it's also

frustrating or I wish it could be different. That it has to be a response, it has to be reactive, and people have to experience these horrible things in order for change to be made, in order for or in order for people to go, hey, maybe we should re examine how often we're testing this particular machine for listeria, or what constitutes an acceptable level of listeria or so on.

ad immunity. And my favorite mention was patho epigenetics. Ooh, but I don't want to step on your toes erin, So why don't you bring us up to speed on where we stand with listeriosis today and also why the heck cellular biologists are so fascinated with this bacterium.

just diarrhea. Oney six hundred cases and two hundred and sixty deaths annually, and as far as I can tell, that statistic does not include necessarily things like early or premature labor or other pregnancy complications that don't result in death of a neonate that would be counted as deaths. So that's not a massive number compared to most of the pathogens that we talk about on this podcast. But

it's not an entirely small number either. When we try and look globally, unsurprisingly we don't have Greade numbers what but the World Health Organization estimates anywhere from point one to ten cases per one million people per year globally. So if we air in math that situation love it trademark air and math, that is anywhere from eight hundred to eight thousand cases globally every year, which is a huge range, but all together numbers that are significantly smaller

than numbers that you mentioned, Aarin. And I think one thing that's really interesting about this is that I talked about the pathogenesis of this and how terrifying and how severe the disease listeriosis is when it causes this invasive infection in people who are susceptible, immuno compromised, or during pregnancy.

But this is still a very rare pathogen and despite that, like you said, Aarin, it's still an incredibly important part of how we make our food safety regulations, which I think is fascinating and it really has sparked continued continues to be a big point of debate. The US actually has I learned, a zero tolerance policy for listeria monacytogenies in industry sampling, which I was shocked by.

global population, it's really difficult. But I do think that it's really interesting that a pathogen that is as rare as listeria when you look at it compared to other food borne illnesses causing hundreds of millions of infections, it still has a really important role to play in making this kind of policy because of how severe it is when it does happen, right, and because like you mentioned it, and we do still see a lot of outbreaks food

born outbreaks associated with specific types of foods, which means that this is a pathogen that could potentially cause quite a lot more morbidity and mortality if a large outbreak were to occur.

that listeria is going to die. But foods like a deli turkey eat or deli ham, any deli meats that you don't cook when you bring home that are cooked and then processed and refrigerated and sold for immediate consumption, those, if contaminated with listeria, can pose a significant risk because that listeria can continue to replicate even if it's at very low levels in that food to begin with, and

then can cause infection thereafter. The same thing is true for milks that are raw or unpasteurized, or cheeses that are not cured, so like soft cheeses that are made from milks that are unpasteurized. Those are some of the highest risk things that we've seen, but we see outbreaks in other things too, like one that's ongoing currently, as we record in Inenok mushrooms in the US often consumed

raw those mushrooms. In twenty twenty two, in the US, we saw outbreaks in deli meats and cheeses like generically just meats and cheeses of deli counters across the country. We also saw outbreaks in some soft cheeses like Breeze and Camembers, and in ice cream. Like you mentioned, there's been outbreaks in various bad salads, things that again are

prepared and ready to eat. So those are the kinds of things that tend to be highest risk, and that's why the recommendations tend to be that people who are at high risk, who are immunal compromised, or pregnant, try to avoid those foods.

and research when it comes to listeria. The most exciting thing is all of the ways in which listeria serves as this model organism that I mentioned in the biology section, which again I had no idea, but I will post a few really great, incredibly detailed papers about the kinds of research being done on the pathogenesis of listeria and what the implications are for what we can learn about intracellular infection in general, as well as our understandings of

cell to sell communication on a broad scale, because understanding listeria infection has implications for understanding the process of infection and dissemination and how pathogens not just evade our immune responses but also penetrate these supposedly impenetrable barriers that are meant to keep them out, but also the way that our cells actually talk and communicate with each other because Listeria hijacks a lot of these mechanisms in our own cells.

So the things that we are learning from listeria are having and I think we'll continue to have implications that go far beyond this one food borne pathogen, which is just it fills me with thrill.

monocytogenies by Mara at All from twenty twenty one. And then of course I want to shout out the classic discovery paper by Murray at All from nineteen twenty six and where I saw the phrase patho epigenetics I just want to shout out was in a paper looking at sort of this like new microbiology and understanding the cellular signaling aspects of Listeria monocytogenies by Cosart and le Breton from twenty fourteen.

in Infection biology. And then I had a few older papers more specific to the symptoms and what we see with disease ats self, as well as the citations for the numbers of epidemiology and all of that. You can find the list of our sources for this episode and every one of our episodes on our website, This podcast will Kill You dot com under the episode's tap.