This Podcast Will Kill You - Ep 114 Listeria: It put dairy on the map

Episode Date: March 7, 2023

For many of us, our encounters with listeria may not go beyond reading the occasional headline about an outbreak from contaminated hot dogs or listening to our doctor advise us to avoid certain foods while pregnant. But as we explore in this episode, the story of Listeria monocytogenes is more complex, scary, and unexpected than you may have imagined. Join us this episode as we trace the dual-natured and sometimes extremely deadly infections this pathogen can cause, examine how the industrial revolution and cattle movements may have altered the landscape of Listeria monocytogenes, and ask why cell biologists are so enamored with this bacterium. One thing’s for sure: this isn’t your typical food-borne pathogen. See omnystudio.com/listener for privacy information.

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Generated assets is an interactive analysis tool. Output is for informational purposes only and is not an investment recommendation or advice. Complete disclosures available at public.com slash disclosures. Hey, everyone. Just wanted to give you a quick content warning here that the first-hand account for this episode does include the death of a parent. So if you would like to move past that, you can skip ahead to about 11 minutes and 15 seconds in. Hi, my name is Denise and I'm here today to talk about the story of my mom and what she went through with Listeria. As a little backstory, my mom turned 80 years old in June of 2022.

She was very, very vibrant. She still worked. She golfed. She was exceptionally active. Some more backstory, she had a regular routine normal colonoscopy in June that showed no ulcer. 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 arthritis and started her on high-dose steroids and methotrexate. At the same time, she had a long-standing

trip planned August 18th through October 9th 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 27 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 24th, 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 28th, she called because she said that she'd started not feeling so good. So then the next day was Thursday the 29th. 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 30th, I received a call at 3 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 urgent 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 IV fluids and repeat the labs. The morning of October 1st, 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 and triaged about three. And then because of just how life in the ER is these days, she got back to a room at like 8.30 at night.

And the doctor saw her at 10 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 3.30 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 103.4. The staff came and drew blood cultures, and she was started on an IV antibiotic cocktail that they do for sepsis of unknown origin.

I got on the plane to go up to Portland at like 9 o'clock in the morning on Sunday. I arrived at the hospital at 11 a.m. She looked like she was going to die when I walked into the room. I worked 11 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 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 in her bloodstream 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 Listeria. It took until 11 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 6.30 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 emboli from the infection. So to see her mental status also improving like that was really amazing. They had given her a medication called Eryxtra 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 count 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 and 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 doctors, the hospitalist and the infectious disease doctor, they were just amazed at how good she was doing. And then at 3.30, 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 a intestinal bleed, and they pass stool, 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, all throughout her large intestine and up to into what they could see in her small intestine, was just riddled with ulcers. On the 14th, she really started bleeding quite heavily and went into shock. And before she actually went into like 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 in 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 26th, she had had 12 units of blood, two failed interventional radiology procedures and three surgeries. Throughout this time with her in Washington, 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 1,100 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 really 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 fore. 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 she was able to see that and she passed away on the night. So we don't know what the source was. We don't know what she ate or how she contracted this. It was a very long month of stops and starts where we would think the bleeding had maybe stopped and then to have it start again when I told her that we had gotten the, air ambulance that we were going to be flying home to California. She said, oh, Denise, that's wonderful. And when she saw her sunset, she said, it's so beautiful. And she is missed every day. And thank you

for letting me share her story. Thank you so much, Denise. Like, I can't imagine. And we really appreciate you being willing to share that story. And we know it couldn't have been easy to do. So thank you. Yeah, thank you. Being able to hear a story of how this disease can really affect people and their families, it's just so powerful. And thank you so much for being willing to be so vulnerable and share that with us. Hi, I'm Aaron Welsh. And I'm Aaron Alman Updike. And this is, this podcast will kill you. Today is a heavy-duty topic. Mm-hmm. Listeria. Yeah, more heavy-duty than I realized. It is so gnarly. So I feel like probably many other people can relate to this when I say that until doing this episode,

Listeria to me was just one of those things that pops up occasionally with like, oh, Listeria detected in this food or that food. And be careful if you are pregnant or, you know, but it was just sort of another foodborne pathogen, which is, you know, they can 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. Right. I did not know the extent of it either, even having been pregnant now twice, and been like, I'm not allowed to eat turkey. I'm so upset about it. But that's what it was to me, right? It was just like, oh, I can't eat turkey and I'm annoyed. But I also did not realize the extent of why.

Yeah. Just how scary it really is. So yeah, we're going to get into it today. We really are. Yeah. But first things first, it feels very strange to dive into like a cocktail or quarantini time. But yet here we go. That's what time it is. It's what time it is. What are we drinking this week? We're drinking the coldest of cuts. We toyed with a lot of different names for this. Last episode was a dairy-filled cocktail because we did vitamin D. So we couldn't do dairy again. No. No. My second favorite name was Don't You Dairy. Which is very good, by the way.

I do love it. And then there was like the salami sling or the salami sour or the cold cut Collins. But I think I like the coldest of cuts. I love it. I love it. Erin, what is in the coldest of cuts? It is a slushy or blended Arnold Palmer with some rum in there, some spiced rum. Serve it alongside a nice turkey sandwich.

Yeah. Or don't. We'll post the full recipe for that quarantini as well as the non-alcoholic placebo rita on our website, this podcast with kill you.com, and all of our social media channels. Oh, more podcast to business website stuff. We've got lots of website stuff. We have transcripts. We have all of our references. We have links to merch to our music by Bloodmobile, to our Goodreads list, to our bookshop.

Dot org affiliate account. You know, we've got lots of stuff. Patreon, I think. I should have kept my post it. It's not here anymore. I lost it in the break. I'm impressed that you went through a list at all, quite honestly. So you win.

Yeah. Yeah. Well, thank you. All right. Well, with that, shall we get into this episode? We shall. Okay. Right after this break.

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That's Q-U-I-N-C-E-com slash this podcast to get free shipping and 365-day returns. Quince.com slash this podcast. So the genus Listeria includes at least 17 different species of bacteria. But the main one that we're focusing on today is Listeria monocytogenes because that's the main causative agent of Listeriosis, which is the disease that we're talking about today. Listeria in general are gram-positive.

This is a gram-positive rod-shaped. So a little bacillus, or sometimes it's called a coxopho. bacillus because it's like a short rod. I don't know. They are a facultative anerobe, which means that they can grow both with and without the presence of oxygen, already cool little bug. They can survive even at very low temperatures, like in the refrigerator or the freezer, and they can continue to grow under those conditions. And they're very resistant to other extreme environmental conditions, like low pH, very acidic environments, or high salt concentrations. So these are very hardy little bugs. Most of the time, they're found living, free living in soil or detritus or water.

And they also readily form biofilms, right? So they can form this entire biofilm that's really hard to get rid of. Erin, what other episode were we talking about biofilms in? I honestly have no idea. Okay. I would have to Google through our transcripts. Yeah, yeah, yeah. But yes.

So that's a lot already that we've already talked about when it comes to this little bacterium. And because of all of these reasons, this bacterium poses a really big risk to the food industry. Because they can survive despite a lot of things that our food industry does to try. to decontaminate everything, right? Like refrigeration, like acidic cleaning 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. First of all, it's really scary. Second of all, I just did a search through our transcripts and Legionnaires disease. Oh, yes. Okay, that does make sense because little biofilms in the like AC equipment.

Mm-hmm. Mm-hmm. If any of you listeners got that without having to search our transcripts. You are better than us. You win. Okay, but this bacterium gets even cooler, or rather it gets even more terrifying. Because while Listeria is a free-living environmental microbe, it also can oscillate between being one of those, something, hanging out in the soil, living and replicating just fine, and then switch to being an intracellular bacterium that invades mammalian host cells and survives and replicates inside of our cells. So it's also found as a transient inhabitant of both animal and human guts. And so there's a lot of evidence that we are all probably exposed to Listeria monocytogenes on a relatively regular basis, and it's a really common pathogen in the environment because of this.

Again, I had no idea. I know, I know, I know, I know. So the way that we get exposed to this in general is through our food. The way that this becomes a pathogen is it's a food-borne pathogen, which means that we eat this bacterium, we ingest it on our food, and it travels through our guts. But from there, it's actually quite different from most any other foodborne illness that we've talked about. Here's why. In general, and this really did surprise me, the symptoms either go incredibly severe disseminated infection that we're going to talk about in detail, or mild, if any, symptoms, and we might never know that you had this as an illness. So let me explain. When you ingest listeria on your food, let's say on your turkey or your cheese or your lettuce even.

Anything really, which is just adds to the scary column. If you have a fully competent immune system, fully competent gut lining, no major risk factors, you may or may not get exposed to enough bacteria, a high, high enough bacterial load to cause an infection that's limited to your gastrointestinal tract, a gastroenteritis. So that might mean that you have some diarrhea or some nausea vomiting. If that's the case, then those symptoms would generally start within about 24 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-borne 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 infection, which we'll get to. Because we just don't have data on it. Most of the people that are getting foodborne illness of any kind, we're never detecting what that pathogen actually is

and they recover with no issues. What we worry about with Listeria, the disease we know of as Listeriosis, is an invasive infection. And when that happens, the symptoms are different entirely, which I think is one of the most interesting parts of the Listeria story, because it doesn't mean that it starts with this food-borne infection. Think of it as two different diseases entirely. Does that make sense? Yeah. So you don't have the one to three day GI symptoms? Not necessarily. Okay. Tell me why.

Why? I don't know. But from what I can gather, there are three major disorders that we worry about that are all classified under this umbrella of Listeriosis. Three like manifestations. One are maternal fetal infections, and this encompasses a lot of different possibilities that we'll get into. Two, bacteremia or septicemia, so infection of this bacteria in the bloodstream. And three, neurolystereosis, or a meningitis picture, infection of our central nervous system. We've talked about other foodborne illnesses before, some of which can pose a risk of invasive infection, like E. coli 0157, for example. example. But with those, what we tend to see is a GI infection. You have these diarrhea, nausea,

vomiting, fever. You're feeling crappy with a GI infection. Your guts are a mess. 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 gastroenteritis, nausea vomiting diarrhea, maybe fever, you're feeling crappy. But the cases that we worry about are actually separate entirely. And the incubation period for these is not 24 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. I see. 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 gastroenteritis picture.

That makes things so difficult, I imagine, for intervention because with something like E. coli, it's clearly a GI bug that's then moving into disseminated infection and more severe infection. And this is like, suddenly here's this disseminated infection, but we don't, there's nothing that tips you off as to what it could be beyond the usual suspects. And Listeria is not necessarily a usual suspect. Nailed it, 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 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. I love the intensity. It's, it is, I was feeling honestly the exact same way. And that's, I couldn't even wrap my brain around how interesting that that part of the Listeria story is. So let's first talk about the three major manifestations of Listeriosis, perinatal infections, bacteremia, 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 10% plus or minus of all Listeriosis cases.

And again, when I say Listeriosis, I just mean these three invasive infections. Think of the foodborne illness as totally separate. Oh, okay. Mm-hmm, mm-hmm. 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 nonspecific.

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 pylonephritis, which is infection of the kidneys. So really that could just be like back pain along with a fever and evidence of an infection. Okay. But with infection during pregnancy, while the infection for the pregnant person is very rarely severe or life-threatening, the problem is that for the fetus, infection only, almost inevitably, 80% of the time or more leads to severe complications. Because this is a bacteria that's crossing over the placental barrier very easily,

infecting the fetus, and can lead to early pregnancy loss or stillbirth, 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 both an early, like, neonatal infection right when that baby is born, they can become infected and have signs of either sepsis or meningitis. 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 hysteriosis as well. So this is another thing where we're seeing a delay between exposure and ramping up and then severe complications. Potentially. It all just depends on the timing of the infection during pregnancy.

So, okay, speaking of the timing of infection during pregnancy, are their highest risk periods? And how long is someone infected with hysteria? And I guess that's such a, that answer is probably super variable. Yeah, it's really variable. And it's even, it's even variable in terms of the timing of infection. Infection at any point during pregnancy, 80% of the time has severe complications. What those complications are going to be will depend on the timing of pregnancy. So more likely to lead to early pregnancy loss if you're earlier in the course of pregnancy, more likely to lead to a neonatal infection if you're very close to the end, etc. But at any time point, we see severe complications for the fetus. Okay. So it's always super high risk. It's 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. These symptoms are not super severe. Like, I'm sure that they are extremely uncomfortable and painful, but they're not necessarily something that's going to look like sepsis or whatever. So how does someone get tested for Listeriosis? Yeah, that's a really good question. And it's likely when there's a complication with the pregnancy. That's when someone is more likely to seek care when something is going wrong with the pregnancy if they haven't already sought care when they had these flu-like symptoms.

And I don't want to downplay how sick someone would likely feel when they 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? 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 65, whether or not they have any immunocompromising 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 immunocompromised 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 lysterosis. 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 30 to 50% of cases of Listeriosis, which is a lot. That's a lot, yeah. With this infection, the symptoms are incredibly nonspecific. And when you read them, they really are just the symptoms of sepsis, which we covered in detail in our sepsis episode.

So it often starts with fever. feeling overall really bad, 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 blood. stream. 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 bractoremia 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 bacteriumia and septicemia, the mortality rate is 20 to 30 percent, and that is even with treatment. It's so scary.

It's so awful. It's terrifying. Yeah. Finally, listeria can also cause a menendritis, or in some cases, a new word. A romb encephalitis. Okay. Which we'll talk more about because that includes the disease known as circling disease in animals. Oh, thank goodness.

I had that written down in my notes and then it just stayed circling. Like, that was all that I. Yeah. Yeah. So meningitis or infection of the central nervous system accounts for, by most studies that I saw, about 30% of cases of listeriosis in adults. So if you've been adding this up as we go, parinatal infection accounts for about 10%, bacteremia, about 50%, meningitis about 30%, and we're left with an extra about 10% of cases that are very,

very rare, and we'll talk about in a minute. And are these mutually exclusive categories? Great question. No. No, they're not. You can certainly have a bacteremia and a meningitis picture at the same time. Okay. Yep. Yeah, yeah, yeah, definitely. So in adults who end up with a meningitis or a meningioencephalitis from Listeria, again, the symptoms are like another meningitis from a viral cause or a bacterial cause. So what that means is fever, headache, stiff neck. If it's infecting the brain itself, you might have things like confusion or even distrullion. Or even distrave. disruption in consciousness.

Usually the onset is a little bit less abrupt than some other more common causes of bacterial meningitis like pneumococcal or meningoccal meningitis. And it's often harder to detect lysteria 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 going to 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 when you look at a picture of a brain, it's like the two tiny balls on the back. And this is a Rombencephalitis. 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 ataxia. You might see cranial nerve abnormalities because your cranial nerves that innervate the muscles and sensory system of your face and neck come out in our brainstem near the serenial. 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 rombencephalitis, and it can lead to very odd behaviors, including circling, where animals walk

in a 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 brain stem. Okay, so many thoughts. Number one, I remember seeing a video of circling ruminants of some kind. I can't remember what it was going around like last fall. And I think that's when we added Listeria as a topic or we were like, oh, for sure, what's going on here? So here's the thing. That video, almost certainly not Listeria. What is it? Don't know. There was a lot of explanations that I found. online and I am not a veterinarian so I'm not going to like try and delve into the nitty-gritty of what those are but the reason that it most likely was not Listeria is because first of all you're

right I wouldn't expect that an entire herd is going to get infected in the exact same way at the exact same time with a pathogen that's an opportunistic pathogen that's not infecting everyone equally well and so that's my other question about that because ruminants because livestock can be infected and be totally fine, and they just shed listeria into the environment. Just like us. Okay, so this would be a case. This would be an individual more likely. Okay.

And this would be an individual that had something else going on that was immunosuppressed in some way. Exactly. Yes. And it wouldn't be walking in a perfect unidirectional circle with all of your friends, like that video of the sheep. that was going around virally, it would be a lot more of that ataxic gate. It would be a lot more like stumbling kind of confused gate. Would it still be unidirectional likely? Yes, because it often, what we see in animals is this asymmetric infection. So you're damaging one side of the brainstem more than the other. And that's why you see like a unilateral picture of infection.

Okay, so let's talk about why the heck it happens there. Do you have an answer? That we don't have an answer to. Okay, okay. Like why that part of the brain? Yeah, and why one side? Yeah, I don't know. Great question.

Okay. So those are all of the different ways that you can get Listeriosis. I did mention the remaining 10% of cases are often localized infections. So you can actually see skin infections, especially maybe. be among people who get exposed from livestock, or rarely other specific organ infections, like an endocarditis infection of the heart or a liver infection or infection of the wall of the abdomen. So we can also see potentially infection in specific organs, but this tends to be very, very rare compared to the other manifestations of listeriosis.

Okay. So how does this happen? Why does this happen? Yeah, it's crossing the placenta. It's crossing blood-brain barrier. This bacterium has a lot of tricks up its sleeve. You nailed it. I didn't realize, something that I didn't realize at all before researching for this episode,

is that because of these traits, Listeria has actually become a model organism of infection and invasion, because it is so good at invading across our normal protective barriers. So in the case of a person who's immunocompromised and exposed to Listeria, Listeria can then cross three, you named them, very important structures that we usually use to keep pathogens out. First, it's crossing over our intestinal epithelium. So it's no longer just limited to our.

our guts. It has a really easy time penetrating these tight barriers. It makes its way into our lymph system and our bloodstream 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 throw

arrive within the cytosol of our cells. Both cells like our macrophages, 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 macrophages do by actually hijacking those macrophages machinery and breaking out of the vacuoles that we've trapped it in and replicate inside of those macrophages. But Listeria can go one step further. They can then actually escape cell to cell.

It is so wild. It's amazing. So they're able to spread directly from one of our cells to another of our cells without having to leave the cell that they've been replicating in. Most of the time, when I've talked about intracellular pathogens like viruses and other intracellular bacteria, I say they replicate and replicate and then they burst out of our cells and they travel through the bloodstream to infect another cell. Listeria don't have to do that part. They can intentionally travel from cell to cell to cell without a cell.

having to burst out and enter our bloodstreams or our lymphatics. And they can do this not just in our macrophages. Our macrophages and other white blood cells intentionally engulf bacteria. So bacteria have an easy time getting inside of macrophages. There's a lot of bacteria we've talked about on this podcast that can survive inside a 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 incredible. It's incredible.

So this bacterium is slow. slowly invading our entire body. Yeah. Hopping cell to cell or sneaking cell to cell to anthropomorphize. And most of the time it's doing this silently, more or less, right? Well, that's a really good question, Aaron. That question has a lot to it. Because the question is, what percentage of the time,

if I'm exposed to Listeria in my turkey sandwich, is it getting through my guts and replicating in my cells without me ever getting sick from it? Does that happen, question mark? Or does it not? Do I have a gut barrier that doesn't allow it to penetrate? And in the case that it does penetrate, does it just take those one to four weeks for the bacteria to replicate to a point at which our body recognizes it and now is causing a response that is illness? right? And that is 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. Okay. And when our body recognizes it as a pathogen, which happens, you know, at a certain point later on when it's things are real bad, what is that response like? Because it's unusual, right?

Yeah. So it seems like one of the biggest risk factors for infection with Listeria, for Lyseriosis, these invasive infections, is lack of a lack of a, adequate T-cell response. So it is T-cells that are primarily the ones that are blocking this infection from happening and responding to this infection when it is established. And so for cases when you lack that response, for one reason or another, that is when you actually see Listeriosis manifest itself. And that is largely because of the way that it's an intracellularity. 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 Listeria. Which is fascinating. It's interesting because it's still a bacterial infection. Yeah. Yeah. And that means presumably that, you know, is there sustained immunity to Listeria? Probably not. I don't think we have any data on that whatsoever, though. Yeah, yeah. Because mortality is really high and because it's a very rare infection still. Oh, thank goodness.

But that is most of the biology of Listeria and the disease that we know of as Listeriosis. It's a bad one. It's a really bad one. It is treatable with antibiotics, and in general, antibiotic resistance has yet to be a huge concern in terms of, like, the normal antibiotics that we would use to treat it. But it tends to respond better to specific antibiotics that maybe aren't used as commonly as, like, general antibiotics if someone comes in with bacteremia or septicemia. So a lot of times we do see delayed. in appropriate treatment because it's a hard disease to diagnose. And which I would guess contributes to mortality rate?

Absolutely contributes to mortality rate. Yes, definitely. So any other questions, Aaron? I mean, I have a lot, but like I'm sure I'll come up with something again at some point. Yeah. Well, can you tell me where this bacterium came from and how long it's been making us sick? And everything that we know about it and how we got here? Oh, yeah, everything. All of it. All of it.

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Okay. And especially you, Aaron, but also you listeners, if you have listened to the podcast before, it involves the discovery of a new pathogenic microbe in the early 20th century. And 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. 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 specifically referring, for the most part, unless I say otherwise, to Listeria monocytogenes. I mean, same. 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 Listeria genus.

some of the non-pathogenic 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. Okay. Yeah. And sometimes it happens, I think, a bit more. methodically, in a bit more of an expected fashion, as much as scientific discovery can be

expected in any case. Listeria monocytogenes, or bacterium monocytogenes, as it was first called, falls into this last category. And I'll tell you how. In 1924, a researcher named Everett George Dunn Murray happened to be looking in the blood of lab rabbits when he found something new. And I say happen to be, but it was really quite intentional. As you'll hear when I read a snippet of his paper, which I felt was like written in a surprisingly poetic way. And I love when that happens with older papers. Like it was, 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 1924, six cases of rather sudden death and rabbits were absorbed. 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 suppose that the disease was of a septicic nature, all cultures from

the heart's blood remained sterile. During July 1924, small, grand positive bacilli were found in films of the acidic fluid in a guinea pig and in smears from the omenum of a rabbit. Side note, I don't know what an omenum is. So I didn't look it up. I forgot to. Do you want me to tell you? Yeah. Yeah, tell me. So it's like this kind of like fatty layer that lays over our guts. It's like attached to the top of your guts and then it kind of lays over all of your intestines and it's a little cushing there for you. It's nice.

It's really nice. Momentum. Cool. All right. Back to the quokes. I have just a few more lines. But Little Heed was taken of these and the heart blood cultures remained sterile. In August 1924, a pure culture of a small gram-positive bacillus was obtained from

the heart's blood of an obviously acute case in a pregnant rabbit. These bacilli closely resembled those seen in the two animals during July, and with their isolation in pure culture, our experimental work began. End 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 grand positive bacilli. 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. And 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, which I thought was really interesting because like 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 leukocytosis. 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. I wonder if the really high monocytes peripheral monocytes that they were seeing were part of what they said, once you see this, you know it can't be anything else because that is true in rabbits, but it is not true in humans. Interesting, yeah. Yeah, that's interesting in and of itself. Yeah, why do different species respond differently to this? But yeah, so not only had other, there's pretty strong evidence for like other people, other researchers having

identified or at least isolated this bacterium before, but either they're being punished for the crime of not writing their paper in English, or they didn't describe it well enough, or it was classified as something else. But then also retrospective analysis of old tissue sections seem 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 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. It was just a really well-written paper. Mm-hmm. Mm-hmm. 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. Monasteland. cytogenes, 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. Lister, who features in our sepsis episode. So go check that episode out if you want to learn more about his story, if you haven't already. Anyway, in the 25 years or so, since Murray first cultured this bacterium, it didn't really make itself known as a pathogen of public health importance. It 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 1929, and at the time it was thought to be related to infectious mononucon. But in general, it was thought to be extremely rare in humans, like 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 1935, who warned that Listeria monocytogenes could be a cause of granulomatous septicemia in infrengthymia in, infants and fatal meningitis in adults. But this warning by Burns was either forgotten about or never heard in the first place until 1951. When HPR Seleger at the University of Bonn, who wrote the textbook on Listeria, like literally,

and I think there's a species named after this researcher as well. when Seleger isolated the bacteria from lesions and 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 83 newborns and stillborn infants who had been diagnosed with, quote-unquote, granulomatous infanticeptica, 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 corinobacterium, and it was only realized that it was Listeria monocytogenes after Sieliger

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 1800s and early 1900s, and hypothesized that Listeriosis may have previously been diagnosed or described as quote-unquote pseudotubriculosis 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 1665 to 1714, had repeated pregnancy losses, stillbirth, neonatal deaths and postnatal meningitis, 17 pregnancies overall with no living offspring. Oh, my.

And some people have speculated that it was due to listeria. I don't know. That's a lot of listeria. It's a lot of listeria. 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 20th 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 20th century. Yeah. Uh-huh. Okay. Big chicken. Big chicken. Yeah.

I mean, and this goes back even further. Mm-hmm. I love talking about the Industrial Revolution and how it changed so much in terms of health and disease, the rise of cities, the growth of hospitals, the commercialization of medicine, the poor air quality, the limited diets, the mass-produced foods, etc., etc. Many pathogens, as we know, as we've talked about, absolutely flourished in these new settings, including Listeria. We now think of Listeria as a pathogen that is 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 1983 after an outbreak of listeriosis among pregnant people and infants with an extremely high mortality rate of 27% of the infants born alive despite aggressive supportive care and 47% overall. 1983. 1983. So this person, particular outbreak was linked to coleslaw that had been contaminated by sheep manure containing listeria.

Gross. So before then, before 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 coleslaw had been processed and they were like, oh, it's in the poop. Yeah. Yeah.

And later on, I'm going to pick back up on some of these foodborne 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 topic. So during this time, as more and more people began to move. 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 processed 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

U.S. where the giants in food industry, who were more concerned with profit than the health of their consumers, actively discouraged any safety legislation from being passed in the U.S. for years, years, decades. Zero percent surprised. Oh, oh, even though it's not surprising, it's 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 horsehairworm swimming in the milk. No, no. Stop it. But then the plaster of Paris made it look farm fresh and straight from the utter. Stop it. Oh, this is worse than the arsenic. I feel like you talked about. Similar things. Yuck.

Yep. I mean, meat production, like, don't even get me started. It was equally appalling, if not more so. There's a reason that Upton Sinclair's The Jungle caused such a stir. No food was safe to eat. Spices were, like cinnamon, was mostly just brick dust, for instance. 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 U.S. Or read the book now if you don't feel like waiting for the episode. Yeah. It's such a jaw-dropping book. Oh my gosh. That's great. 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 2021 by Mora et al traced the global spread of Listeria, particularly one clonal group, L-M-C-C-1, 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-19th 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 1870, 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 pluridomonia and foot and mouth disease. It's all about diseases. It's always. It's always about diseases. It is. We're not biased or anything. But this trade agreement isn't just a matter of a few head of cattle. According to this paper, it led to a 1,000-fold increase in the amount of cattle moved from North America 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 1895 to 1903 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 U.S. 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 country or whatever. Oh my gosh, that's really, really cool that they had enough data to be able to see that.

Right. And then it keeps going. When trade resumed and cattle farming and food industrialization intensified around the mid-20th century, boom, you can see that. These changing practices are reflected by what's happening also with this clonal group, which is so amazing. And has also been seen for a few other foodborne pathogens with a zoonotic reservoir like E. coli 0157H7. So it seems pretty likely to me that the apparent rise in Listeriosis around the mid-20th 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. Yeah. And changes in food production that just favor this pathogen's growth. Just favor contamination. Like actively promotes contamination.

But, I mean, it certainly did help once people knew what they were looking for. It wasn't until the 1980s that another change was made that we can see in these clonal groups, which is the stabilization. of the clonal population. And that happened around the mid-1980s, which is after people realized that it was tied to food production and certain food practices. And so they started to institute 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. Right. 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 sanitary 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. Yeah, and to be able to track like pathogen diversity like that, I really, that's very cool. Yeah, it's, it's beautiful. But not only is it interesting or beautiful, it also helps us with control or prevention today. Since Listeria is not transmitted human to human and mostly comes from contaminated food

sources, even if we don't necessarily always or even often know the source of the contamination, and because of the biology of this pathogen, it's clonal nature, the fact that at the local level certain genotypes dominate, we can use all this information to trace persistent sources of infection, like whether it be from a particular herd, maybe there's a, a really high prevalence in 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 1980s 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 1983 Listeria outbreak in Canada tied to contaminated coleslaw, 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 49 people, primarily infants and immunosuppressed adults and a fatality rate of 29% 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 cytogenes, because remember the first one was Kohlslaw.

Right. And so this one really put dairy on the map. And sure enough, a couple of years later, soft cheese was the culprit in a large outbreak of Listeriosis in California involving at least 101 human cases and 50 or more deaths. Oh my. That's massive. Massive. Ice cream was next on the chopping block when the bacterium was found in large quantities of a well-known brand.

They didn't name it in the paper. And there have been subsequent ice cream-associated outbreaks as well. 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, the 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. Yeah. 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 monocytogenes in nearly half of the black bears that they sampled in parts of the eastern U.S. Bears. Oh, my gosh.

I know. And also have 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 in reported Listeriosis cases in the 1990s, from 11 per million population in 1988 to four cases per million in 1998. So it's like, that's a pretty substantial decline. In 1999, a U.S. wide outbreak involving 101 cases and 21 deaths linked to hot dogs stopped Listeria from dropping further down on the foodborne 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 reexamine how often we're testing this particular machine for Listeria or what constitutes an acceptable level of listeria or so on. I wish that we could be proactive. A whole another set of discussion, isn't it? Well, that being said, I think it is important to recognize that we have come a long way, not just in food safety practices, but also in our understanding of Listeria monocytogenes. and as you mentioned, not just as a pathogen of public health importance, but also what it can tell us about things like cell signaling, surface proteins, innate immunity, and my favorite mention was pathoepigenetics.

Ooh. But I don't want to step on your toes, Aaron. 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? Mm-hmm. I can't wait to. We'll take a quick break and then get into it. In the U.S. annually, the CDC estimates that there are 1,600 cases of listeriosis. So again, that means invasive infection, not just diarrhea, 1,600 cases, and 260 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. Yeah. But it's not an entirely small number either. Right. When we try and look globally, unsurprisingly, we don't have great numbers. What? But the World Health organization estimates anywhere from 0.1 to 10 cases per 1 million people per year globally. So if we err in math that situation. Love it. Trademark. Aaron math. That is anywhere from 800 to 80,000 cases globally every year,

which is a huge range, but altogether numbers that are significantly smaller than numbers that you mentioned, Erin. 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, immunocompromised, or during pregnancy. But this is still a very rare pathogen. And despite that, like you said, Erin, 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 U.S. actually has, I learned, a zero tolerance policy for Listeria monocytogenes in industry sampling, which I was shocked by. Yeah, me too.

How often are we testing, et cetera? I don't know. But it does have a zero tolerance policy. Most other countries don't necessarily have a zero tolerance policy because that's really difficult to achieve. So deciding how do we balance risk of infection versus being able to feed a growing 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 foodborne 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, Aaron, we do still see a lot of outbreaks, foodborne 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. In terms of the types of foods that are highest risk, I think you mentioned a lot of them already. But you can think of them as things that are already prepared and then refrigerated and then you eat them, right? because despite how hardy of a bacteria, Listerio monocytogenes, is, it can't survive the cooking process.

So foods that you take home and cook, like most meats that you're cooking thoroughly, even if they have listeria on them, if you're cooking them thoroughly, then that listeria is going to die. But foods like a deli turkey 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 unpasturized 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 Inoki mushrooms in the U.S. Often consumed raw, those mushrooms. In 2022, in the U.S., we saw outbreaks in deli meats and cheeses, like generically, just meats and cheeses of deli counters across this country. We also saw outbreaks in some soft cheeses like breeze and camemberes and in ice cream, like you mentioned. There's been outbreaks in various bagged 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 immunocompromise, who are immunocompromise, or pregnant try to avoid those foods. That's hard to do. Yeah, it's really hard. And it seems like it could also be an issue of access where it's difficult to buy food to then prepare rather than getting like who has the time or it's more expensive sometimes to buy food to then prepare. And so that's an interesting, I think, component of it. Yeah, absolutely, absolutely. But that's kind of where we stand with infections, with listeriosis today across the globe.

A lot left to be desired, I feel like. But I think we're in a very interesting place where it's definitely still a pathogen of big concern, especially for the food industry, and it's something that still shapes how our food industry operates and makes decisions globally. Yeah. I do think in terms of even bigger picture future directions 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 cell 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. Yeah. So that's Listeriosis, Listeria monocytogenes. There's a lot to it. There really is, and we probably missed a lot. We probably did. And you can check for us by taking a look through our references. Yes. So I have several. I have a bunch, but I will shout out just a couple in particular.

So the one that was tracing the spread of that one clonal group of Listeria monocytogenes by Mora at all from 2021. And then, of course, I want to shout out the classic discovery paper by Murray et al from 1926. And where I saw the phrase pathoepigenetics, I just want to shout out, was in a paper looking at sort of this new microbiology and understanding the cellular signaling aspects of Listeria monocytogenes by Kosart and Lebraton from 2014. I have a paper by it sounds like one of the same authors. The two papers that were very detailed on where we stand with understanding this pathogen as more than just a pathogen. One was from 2018 in Nature Review's microbiology called Listeria monocytogenes toward a complete picture of its physiology and pathogenesis. And the other was from cellular microbiology in 2020 called Listeria monocytogenes, a complete picture. model in infection biology. And then I had a few older papers more specific to the symptoms and

what we see with disease itself, 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 with kill you.com under the episodes tab. A huge and heartfelt thank you again to Denise for sharing. your story with us. It's, we really can't thank you enough. Yeah, really. Thank you also to Bloodmobile for providing the music for this episode and all of our episodes. And thank you to Leanna Squalachi for the excellent audio mixing. You're the greatest. Thank you to the exactly right network. And thanks to you, listeners, we hope you like this one. Hope you found something new. Yeah,

isn't it? And something. I did. So did I. Lots of New. Lots of new. And as always, a special thank you to our patrons. Thank you so much for your support. It really means a lot. It does so much. Okay. Well, until next time, wash your hands. You filthy animals. This is Bethany Frankel from Just Be with Bethany Frankel.

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