This Podcast Will Kill You - Ep 61 Typhoid: There's Something About Mary

Episode Date: December 1, 2020

Your long wait is finally over - the season four premiere of This Podcast Will Kill You has arrived! And to mark the special occasion, we’re taking on a topic that is both classic TPWKY material as well as enormously relevant to current discussions in public health. Typhoid fever has been the cause of untold death and devastation throughout human history, and despite our advancements in both treatment and prevention of the disease, it continues to wreak havoc on millions of people around the world every year. This week, we take a trip through the terror of typhoid, starting by tracing the journey this bacterium makes through your body before taking a look at the long history of typhoid in human populations. And what story of typhoid would be complete without Typhoid Mary? We examine the plight of Mary Mallon in the context of today’s COVID-19 pandemic and discuss the tension that often arises between individual and community rights in matters of public health. Finally, we wrap things up with a look at the current status of typhoid fever around the world (spoilers: it’s pretty terrible) as well as some promising developments on the horizon (spoilers: okay, it might not all be bad!).We are so excited to be back with you this season, coming through your headphones with some casual chat about diseases throughout human history! As always, we are happy to hear from you about what you’d like us to cover, so send any suggestions through our website contact form. For your TPWKY merch needs, check out the sweet offerings on our shop's page. And for extra reading, you can find references for each episode on the episode page or check out our bookshop.org affiliate page or our Goodreads list. See omnystudio.com/listener for privacy information.

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Terms and Conditions Apply. Visit blueapron.com slash terms for more information. I'm Amanda Knox, and in the new podcast, Doubt, the case of Lucy Letby, we unpack the story of an unimaginable tragedy that gripped the UK in 2023. But what if we didn't get the whole story? Evidence has been made to fit. The moment you look at the whole picture, the case collapsed. What if the truth was disguised by a story we chose to book?

Oh, my God, I think she might be innocent. Listen to Doubt, the case of Lucy Letby, on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts. This is Special Agent Regal, Special Agent Bradley Hall. In 2018, the FBI took down a ring of spies working for China's Ministry of State Security, one of the most mysterious intelligence agencies in the world. The Sixth Bureau podcast is a story of the inner workings of the MSS, and how one man's ambition and mistakes opened its vault of secrets. Listen to the sixth bureau on the Iheart radio app, Apple podcasts, or wherever you get your podcasts. Number one, the camp at Chickamauga was a perfect hell on earth.

War itself would have been a paradise compared with the peace of this camp. I saw many awful sites there, men dying under the trees for the want of a glass of water. I found there men who had been sick with typhoid fever for days and who had not received medical attendance. No one had even taken their temperature. It was awful. For 500 men in hospitals, there were only a dozen attendants. The water from the creek was simply mud, and yet the boys had to bathe in it and drink it. Everything about the camp was badly managed. As for the food, there is only one way to describe it. It was rotten. Number two, someone is to blame for keeping an army of 45,000 men at a camp where all the water was unfit for a dog to drink, where there was no

drainage, no proper food or medicine, and where the conditions were so unhealthy that every man of 45,000 had intestinal troubles. Three-fourths of the army slept in little dog tents, as we called them. They were five feet long and four feet high. There were no cots. The men slept on the ground, and it rained nearly all the time for six weeks. Our division hospital was arranged to hold 200 men, but we had over 500 sick men in it. Each tent was arranged to hold six men, but we had 10 and 12 crowded in. There were not cots enough, and sick men had to lie on litters on the wet ground sometimes for a week. The sick came in 50 and 75 at a time, and there were no cots, no medicines, no food for them, except the regular army rations issued to well men. The men detailed for nurses

were the poorest soldiers in the camp. They nursed the sick eight hours in the day and then worked three hours digging sinks and trenches and cleaning up the camps. Number three. In the camp of the third United States volunteer cavalry, we found the sinks full to the top with fecal matter. Soiled paper was scattered around the sinks

and the woods behind the regimental camp was strewn with fecal matter. The second Kentucky volunteer infantry was located in the woods. Fecal matter was. was deposited around trees and flies swarmed over these deposits not more than 150 feet from the company mess tents. The odor in the woods just outside of the regimental lines was vile. Yeah. Yeah.

Why are they pooping in sync? There was nowhere else to poop. Okay. Dig a hole? What is happening? But all the holes got filled either with poop or with water and then the rain water would bring. make the poop rise to the surface and spread around. That's atrocious. Yeah. So that was from the report of the commission appointed by the president to investigate the conduct of the war department in the war with Spain.

Essentially, the Spanish-American War, which reports from that around 1900 is one of these reports from all made. Yeah, a few different excerpts. I thought it was more fun to do a little smattering of poop stories. essentially yes and you'll hear why i pick the spanish-american war for the subject of today's episode um later on but first hi i'm aaron welsh and i'm aaron oman updike and this is this podcast will kill you and we're back with season four we are back and i'm very excited i think we definitely needed that break. Oh, big time. Yeah. So we appreciate you guys for being patient and sticking with us. Yes. Thank you. And yeah, letting us get a little bit of a time to take a breather.

Yeah. And, yeah. Well, and also get a bunch of fun new episodes lined up for you. Oh, so many fun new episodes. Yeah. Yeah. Speaking of fun new episodes, what is the topic of today's episode? Maybe our break was too long. No, no. I actually love that I feel like most of the time lately our first of the time lately are first hands completely give it away. And now it's like suspense has been building for like two whole minutes. Yeah. Well, I guess if if no one clicked on the title of the episode, maybe there's suspense. If it auto played. But today we're talking about typhoid fever. Oh, typhoid fever. This one has been a long time coming. Oh, very long time coming. I am super excited to cover this one because typhoid fever was sort of the episode, I feel like, that really changed our lives.

Yes. It changed our lives a thousand percent, even though we have not yet covered it. Yeah. Because typhoid, the story of typhoid Mary is the story that Georgia Heartstock told when she first gave us a shout out on my favorite murder, which is like what led to like our lives changing forever. All the way back, in case you're interested in listening, all the way back in episode 105, titled Proclensity, I looked it up and I listened to it again. It's a good episode. For research for this episode. Yeah. Yeah. This is definitely like a full circle moment. We've been waiting for this episode since like 2018.

2018, yeah. I'm just so excited for it. Me too. But before we get into the actual meet of the episode, we do have some pieces of business. Starting with... Quarantini time. Quarantini time.

Erin, what are we drinking this week? Of course. We could be drinking nothing other than a Bloody Mary. Bloody Typhoid Mary. Bloody Typhoid Mary. Not just any Bloody Mary? Not just any. This one is titled differently.

But yeah, other than the title, it is essentially a Bloody Mary. Who doesn't love the Bluette? Bloody Mary. You can pick and choose whatever pickled vegetables you want to put in there. It's tomato juice. It's vodka. It's, you know, Worcestershire sauce. It's hot sauce. It's whatever you want to put in there. It's how you like a Bloody Mary. Yeah. An entire like hamburger on a stick. Yeah. Anything you want to put in there, we will post the recipe to the Bloody Typhoid Mary as well as the non-alcoholic placebo rita on our website. This podcast will be a podcast. kill you.com as well as on all of our social media channels.

What other business do we have to attend to, Erin? Well, let's see. Let's go over the usual suspects. I mean, number one, we've got merch. We've got some super cute new things that are here. Very new things. Very exciting things, in fact. The amazing artist, Holly Sullivan, did some new designs for us, including, and you can get prints of her designs right now and stickers of Yersinia Pestis, 80s Egypti, of the influenza virus, of Giardia, Gerardia. However you like to say it. And then there's also other really cool things.

Like one of my favorites is the Quarantini Time T-shirt. It is so soft. And I also have to admit to always wearing the hoodie around. It's like the perfect weight. And then I drink out of the pint glasses and the socks are. are just too cute. I can't handle it. We also heard you guys when you asked for face masks, since those are now pretty much a staple of everyone's wardrobe. So we have two different face masks, including one that says, wash your

hands. You have filthy animals. They both do. Oh, they both do. They are super cute. I really, I love them all. So yeah, go check it out. You can get to it by the This Podcast Will Kill You.com website. Click on the merch tab. Yeah. Great. Let's see. Okay, more business. We can run through the rest of the usual suspects, which includes, hey, check it out. We've got a bookshop.org affiliate account. So if you're interested in doing any additional reading on any of the topics that we cover, we link to the books there, also through our website. And we also have a good reads list. So check it out, too. Other people can add suggestions there. So you get like a whole smattering of both fiction and nonfiction disease readings. It's pretty good. cool. And if you would like alcohol-free versions of these episodes, maybe you're a teacher, you want to use these for whatever reason. Maybe you just don't want to hear us talk about quarantinis. You can find those as well on our website. This podcast will kill you.com. And then we have a couple of new announcements. So the first is that we are going to be picking up again

our anatomy of a pandemic series, which covers the COVID-19 pandemic. So, We stopped releasing episodes in May, and now we are going to take some time to revisit some of these topics. You know, what have we learned so far about the virus? Everyone wants to know about the vaccine and where we stand with that. And so we are going to be putting those out as we work through these normal episodes. So don't worry, the normal episodes won't be interrupted. And we also still have the first, the COVID-19 first-hand account submission form still active. So if you would like to share your story potentially as a firsthand account in one of these episodes,

please head to this podcast Will Kill You.com and click on the COVID-19 firsthand tab at the top of the page. Is that all the things? I think that's it. I'm exhausted. All right. Let's circle back around tomorrow to pick up the actual episode. Perfect. Good idea. Good idea. But I guess, yeah, can we finally start talking about typhoid? Yes. I think we are ready. We'll take a quick break first. Great. Dinner shows up every night,

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No, no, it's plenty complicated. Oh, good. It is a very classic TPWKY feel, which is kind of fun. It is. And why we chose to do it for our fourth season premiere. Exactly. It's a very classic feel, but then it's also, well, I'll get into it. And you'll see what I mean by specific, okay?

Okay. Okay. So typhoid fever, which is also called enteric fever, depending on where you live, is the disease that is caused by a gram-negative rod-shaped back? whose full name is. Are you ready for this? I know you know this already, but I know. It's a big one. It's a mouthful. Salmonella, enterica, subspecies, enterica, serovar, typhi. That's what I mean by specific. I don't quite understand why. Why? Okay. What is a sarovar? Great, really great question. I'm so glad that you asked it, Aaron. You know I was going to.

Yes. So first of all, we're just going to call it by its shorthand name Salmonella Typhi. Okay, that's how you can refer to it. Now, there are something like 2,500 different serovars of salmonella, salmonella, and terrica even, and at least 50 of them are pathogenic, although not all of those are pathogenic to humans. So you asked how, like, what makes the serovar? You can kind of think of it like, you know how we name influenza strains by their H and their N? Yep, okay. So serovars are differentiated by, from each other, by those specific antigens on their surface. So in the case of salmonella, it's their lipopolysaccharide, which is an O antigen, and

their phlegella, flagellular antigen, which is an H antigen. So that's how we identify them. Interesting. You'd like to know the serivar name of Salmanilla, Saravar Typhi. It's 0912 V-I-D-D-D-D-D. That's an easy thing to remember. Right? Yeah.

Okay. So I'm going to start off with a side note. There's another serivar, a couple of other serivars, actually, that are called paratyfi. So there's paratyphy, A, B, and C. this seravar causes a very similar but generally more mild illness. And so the term enteric fever usually encompasses both the diseases caused by salmonella typhi and salmonella paratyphi. So we're going to try and stay as specific as possible in this episode and really just focus in on salmonella typhi or typhoid fever. Cool. Gotcha. Cool. So salmonella typhi is what is referred to as a host

restricted pathogen. So it primarily infects just humans and then also like chimpanzees. All right. So how is it transmitted? I know you know. And everyone that listened to the first hand probably has a guess. I mean, if you're playing bingo with a number of times that fecal is going to be said in this episode, like, it's a lot. Yeah, fecal oral. So poop in mouth, wherever poop can end up, then ends up in your mouth that you can get infected. Okay. One thing that's important, and I think this is actually really interesting, considering that this is a fecal-oral transmitted parasite, is that salmonella is actually really acid labile,

so it does not tolerate the environment of your stomach very well at all. So that means that the infectious dose is really, really high compared to a lot of other bacteria and viruses that we've talked about on this podcast. Interesting. Like how high? At least 10,000 bacteria to cause an infection. And even at that number, the attack rate, so the percentage of people who would actually get sick, is low, like, 10 to 20 percent at that infectious dose. Okay. How much bacteria is an infected person or a carrier shedding? Such a good question. I don't even know if I know the answer to that. Let me scroll through my notes.

Like in an average poop. In an average poop. That's a good. good, Erin, what a good question that I don't have the answer to in all of my notes. Just FYI, guys, we just spent a little bit of time both looking for the answer. I mean, like, not that long, but, you know. More than a few minutes. We spent more than a few minutes and we couldn't find anything. And so we just think it's safe to assume that it's probably a lot. It's got to be a lot.

There've been a lot of typhoid fever epidemics. It's got to be a lot. Because it takes a lot to get you sick and you poop a lot when you have typhoid fever. So, you know, and it's a salmonella bacteria, which reproduced very quickly. So a lot. A lot. Hey, if somebody can find the actual number, that would be super cool. Would love that actual number.

But what I did want to say about this is that what's really interesting is that, that the smaller, the infectious dose, the longer the incubation period. So the longer between when you first get exposed to when you start to show symptoms, which is logical, but it's nice when we can see that in data. Cool. Okay. Yeah. So the incubation period, that time from infection to symptoms, usually is between five and 15 days, but it can be quite a bit longer, like even a month or more. Gotcha. Okay. So let's talk about the symptoms of typhoid fever, shall we? Let's. Okay. The classic description goes something like this. It starts with a fever. Fever. But not just any fever, because we have to get specific. This is a fever that gets progressively

worse. It's called a step ladder or a stepwise fever. So once it begins, it remains high. It's and then progressively rises over the course of two or so weeks before it peaks and then stays pretty high, like a plateau phase. Huh, okay. Like how high? Good question. Not bonkers high, like we're not talking 106, but a fever is classified as 100.4 Fahrenheit or 38 Celsius.

So it'll start there just like a low-grade fever and then progressively just get higher. I don't know what the maximum peak is, probably depends on the person, but we're not talking like 106-107. It's just a slowly progressive fever. And what's important is that it stays high. A lot of other diseases, you might have a fever for part of the day, and then part of the day your temperature will go back down. With typhoid, once your fever rises, you stay with an elevated temperature. Okay. Okay.

And the other classic symptom that's very interesting is that, and oh my gosh, Aaron, please don't ask me why this happens. Okay, just I'm forewarning you. But classic typhoid has what's called a relative bradycardia. So that means that your heart rate is slow. And normally, when you have a fever, a normal physiologic response would be your body going, hey, I'm feeling stressed out because my temperature's high. So my heart rate is going to increase because of that high temperature.

But with typhoid, it doesn't do that. Your heart rate stays low. I am bursting with questions. How dare you censor me? Okay. I won't ask why. I will ask, are there other diseases or other times that fever occurs when the same thing happens? There are some others, absolutely.

This isn't the only thing that causes this, but that's one. of those classic findings. Okay. Okay. Wow. I know. Okay. All right. Now, that's the initial phase. Okay. So it's like this two weeks of increasing fever. In the second week, people might start to get a faint rash on their trunk. There are these little salmon colored spots. Pretty sure that's not why it's called salmonella, though. Right? Okay. And then in the third week of illness, you often get abdominal pain. You can get either diarrhea or constipation, which is interesting. We'll talk more about that later. Bleeding from the intestinal tract, often you can get secondary bacteremia.

So if this bacteria enters your bloodstream and starts to replicate in your bloodstream, that's what bacteremia is. and sepsis, almost everyone will get hepatitis and a painful hepatospinomegaly, which is a fun word we often say on this podcast. So swelling of your liver and spleen. And now this I want to put a pin in so that you remember it, because we're going to talk more about it. But salmonella typhi is also a cause of acute colisestitis, aka gallbladder infection. Okay. That's important. Just remember it. Now, this is not a bacteria that tends to infect your nervous system. So neurologic manifestations are pretty uncommon. It's not impossible. But when you have them, they look more like febrile seizures

and young children, which happens with a whole bunch of different diseases. And then it is possible to have other more serious complications like myocarditis, but this is really rare. So that would be if it infects your heart. But most of the time, this is a gastrointestinal tract disease. So if you don't die from overwhelming sepsis and shock or from your intestines becoming perforated and just like exploding your gut juices everywhere. My God. Then over a period of weeks to months, your symptoms gradually begin to resolve if you do not die. Okay.

over a period of weeks to months. Weeks to months. This is a long-lasting infection. So the big question, in my mind, is what makes salmonella typhi so different from all the other serivars of salmonella enterica, right? A lot of other species of salmonella, even salmonella enterica, can infect us and maybe we get like the poops from it. But salmonella typhi causes this really disseminated infection. It's mostly GI symptoms, but the first symptoms that you see are this fever, which tells us that it's affecting a lot more than just our GI tract. Yeah.

So, why? Yeah. I ask myself the questions that I can answer. So the difference really is because, salmonella typhi is this host-restricted pathogen. It can very quickly invade through our gastrointestinal walls. So it is not limited. It's not causing an infection that's only in our GI tract. Exactly how this happens, we still don't fully know, but we do know that it's at least in part due to the bacteria down-regulating our immune response.

So here's where it gets interesting. Okay. In our GI tract, we have these things called Pires Patches. I feel like we've talked about them a little bit on this podcast before. But they're basically like lymph nodes in the walls of our small intestine. So it's where like our white blood cells hang out. It's like the immune center of our GI tract. Our GI tract has its own little immune system.

Oh, it's like a big deal. It's a very big deal. Yeah, it's very cool. So, salmonella actually invades through these pyre patches. So this is the area of our small intestine where it makes its way into our body. And what's very cool is it actually uses the same channels to enter through our cells that are missing in people with cystic fibrosis, those C. F-T-R channels. Right. Right. Cistic fibrosis trance membrane receptor, I think. So those also, you might remember, are channels that are important in another bacterial disease cholera. Yeah, yeah. I was

going to say, isn't that when we talked about pyres patches? It could have been. I don't actually remember. That was a long time ago. That was a long time ago. But, so these pyres patches, which is where our white blood cells hang out in our intestine are where cell manila first invades. So that's where it basically makes its way through the wall of our intestine, through that epithelial cell layer and into our bloodstream. And it gets better. Salmonella typhi is also facultatively intracellular. What that means is it can live inside of our cells and guess which cells it likes to replicate inside of. White blood cells?

Oh, white blood cell, Aaron. Our macrophages. Right? So that is how it's able to very quickly establish an infection outside of our intestine. It invades and replicates within our own white blood cells and then travels literally wherever white blood cells go. And because of that, it tends to cause infection. So basically, it'll...

You get infected by eating this bacteria essentially, right? And then it travels through your gut into your small intestine, invades through the wall of your small intestine, makes its way into your white blood cells, travels with these white blood cells to a few specific places where white blood cells hang out. The liver, the spleen, the lymph nodes, and the gallbladder. And then from all of these tissues, the bacteria is continually proliferating. it re-enters the bloodstream, and that's when you start to actually see disease. So that's why you have this time lag, right? Right. It's got to make all those journeys and bulk up its numbers.

Exactly, exactly. And then eventually, because it's infecting the liver and the gallbladder, from there the bacteria actually reenters the intestine, and that's when you start to see those abdominal symptoms. And so that's why those abdominal symptoms, like diarrhea, abdominal pain is even later in the course of disease, even though you got infected from your GI tract to begin with. Gotcha.

Okay. And that's when the most serious complications and the most life-threatening complication can occur, which is intestinal perforation. And the reason that that happens, and this is so bizarre, it's thought. And we, again, still don't 100% understand this. But the bacteria, once they re-infect again your intestine, cause tissue death of those pyres patches. So where they initially invaded, they come back in and they kill off enough cells in the wall of your intestine that they make it so that that wall is weak and then eventually can perforate. And that has a mortality rate of like 40 to 80%.

Like, that's fascinating because you would think that there would be like a trigger. Like, clearly they're doing something different. Mm-hmm. They're totally doing something different. And it's quite rare. This only happens in like less than 5% of cases. Okay. Okay.

Listen, we haven't even gotten to the most fascinating part of sale manila typhi. I am very excited. Let's go. Okay. That is that so many people can become infected. and maintain a chronic carrier state without ever showing symptoms of the disease. Oh, yeah. Okay.

Oh, yeah. About 25% of people who are chronic carriers never have any symptoms of disease. Yep. We all know this. This is the story of typhoid Mary. Aaron's going to tell it to us in a lot more detail. But the real question that I need to answer is how on earth could Mary and others have been spreading this infection for so long without ever even knowing they were infected?

It's, I don't, I don't know. I want to know. Tell me. All right. So a proportion of people who get infected with seminal tify won't ever show symptoms. That's fine. About three to five percent of people overall who get infected with semonella typhi go on to become chronic carriers. So where is this bacteria hanging out, whether or not you've ever shown any symptoms? And the, you're, answer is the gallbladder, Aaron. Oh, okay. So in some people, and again, this is also still something that we don't 100% understand, but we have a much better understanding now than in Mary's time, for example. I mean, yeah. So we know that salmonella typhi can invade the gallbladder. It can cause colicitis, which is like an acute infection.

But in some people, it can essentially start to form a biofilm. So it doesn't just invade the cells of the gallbladder wall, but actually forms its own biofilm. And this happens especially in people with gallstones, which as it turned out, happen to be a medium on which seminala typhi can persist and grow and form a biofilm. What is a gallstone made of? Often cholesterol.

There's a few other things that it can be, but most of the time it's cholesterol. Okay. Interesting. So that's kind of the main thinking that it's gallstone related, biofilm related, something like that. And we know that it definitely causes chronic inflammation because infection, chronic infection with salmonella typhi is pretty strongly associated with gallbladder carcinoma. So cancer. And we know that cancer and inflammation often go hand in hand. But it's a little bit more complicated because at least in some cases, colisestectomy, which is the surgery that we do to remove the gallbladder doesn't always resolve the carrier state.

Right. And also, not everyone that has gallstones becomes a typhoid carrier. A lot of people have gallstones. Not every person with gallstones that gets infected with salmonella typhi is necessarily going to become a salmonella typhi carrier. So we still don't fully understand the process, but we at least know more. Is it treatable, Erin? Oh, great question. So it is treatable.

And the good news is that treatment is extremely effective. That's great news. Yes. It's with antibiotics. without any treatment, typhoid has a mortality rate of between 10 to 30 percent, so pretty deadly disease. Very deadly. Like, wow.

Right. With treatment, mortality rates, estimates are like 1%. So still not perfect, and I would say 1% is still pretty high. But that's what the kind of global estimates are. And we'll talk a lot in the episection, but the short answer is like we have a very poor understanding of the global incidence of typhoid fever. Yeah, okay. I kind of figured that. Yeah, very poor understanding. The good news is that in addition to treatment, there are vaccines. There are two different vaccines that are widely available. One is a polysaccharide, so it's like a sugar

that's found on the outside of the bacteria. That can be used starting in children at age two, and children are important because a lot of typhoid fever happens in children. It's really a disease of childhood in a lot of places. That one has to have boosters every two years because it doesn't have a very long-lasting immunity. And then there's a live attenuated vaccine. So it's a live bacteria that they've grown in a lab to be less virulent. So it doesn't cause severe illness, but it still gives you protection. That one, you can't give it to kids under six. So it's only for older kids and adults. And it needs boosters every five years. But we'll talk in the current event's about a very exciting new vaccine.

Oh. That's super new. That's very exciting. That's fun. But we can't talk about it yet. So, Erin, where did this bacteria come from? What's it doing to us? I am very excited because this is going to be a good one, but we have to take a short break first.

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The internet turned on him. If I could press a button and rewind it all I would. But what happened to Clayton after the show made even bigger headlines. It began as a one-night stand. and ended in a courtroom, with Clayton at the center of a very strange paternity scandal. The media is here. This case has gone viral. The dating contract. Agree to date me, but I'm also suing you.

Please search for it. This is unlike anything I've ever seen before. I'm Stephanie Young. This is Love Trapped. This season, an epic battle of He Said She Said, and the search for accountability in a sea of lies. Listen to Love Trapped on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. In 2023, a story gripped the UK, evoking horror and disbelief. A nurse who should have been in charge of caring for tiny babies is now the most prolific child killer in modern British history. Everyone thought they knew how it ended.

A verdict, a villain, a nurse named Lucy Leppie. Lucy Letby has been found guilty. But what if we didn't get the whole story? The moment you look at the whole picture, the case collapses. I'm Amanda Knox, and in the new podcast, Doubt the case of Lucy Lettby, we follow the evidence and hear from the people that lived it, to ask what really happened when the world decided who Lucy Lettby was. No voicing of any skepticism or doubt.

It'll cause so much harm at every single level of the British establishment of this is wrong. Listen to Doubt, the case of Lucy Lettby. be on the Iheart radio app, Apple Podcasts, or wherever you get your podcasts. So I talked a little bit at the very beginning of the episode about why we are so excited to do this topic, typhoid. And so not only is this like the full circle moment of like, oh, you know, we're finally doing the thing that like totally changed our lives forever, thanks to Georgia and Karen on my favorite murder. But also typhoid fever is, like first season TPWKY.

Totally. It's like a big deal. It's a classic disease. It's like one of the, you know, big names. I'm expecting like Ebers Papyrs, Papyrus, ancient Rome, et cetera, et cetera, pooping in holes, all of it. I mean, we've already got the pooping and holes. We started off good.

Let's just see what else we've got here. But, you know, in addition to that, I, as I read more about this, history of typhoid and particularly Mary Malin, who gave rise to the term typhoid Mary, I realized just how relevant her story is to what's going on today and the enormous conflict between public health and civil liberties that can emerge sometimes. And finally, just how important science education and science literacy is to reducing that conflict. Yeah, I'm excited. So let's dive in.

Let's do it. You can probably guess that typhoid fever has been around for millennia. Yep. Evolutionarily speaking, some researchers believe that it originated in Indonesia, like thousands and thousands of years ago, but it would have spread pretty easily and rapidly around the world as travel became more widespread. And one interesting thing to note is that there doesn't seem to be a whole lot of genetic. variation among strains geographically, with the exception of antibiotic resistant strains, which is thought to point towards the importance of carriers in perpetuating the disease.

If that makes sense. So there's not a whole lot of selection pressure by which hosts survive or whatever because carriers are there. Right. There's always carriers to just sort of keep the disease slowly moving through populations and around the world. Really interesting. I never thought about being able to...

Yeah. Yeah, that's pretty cool. It's cool. And I know that you were hoping for like the Ebers Papyrus and, you know, ancient Roman stuff. Yeah. And so like I can't explicitly say no, it wasn't written about. But, you know, it's a very, like as a GI illness, it's like fairly, you know, it's like fairly, you know, it's one of many. People had a lot of runny poops and, like, died from diarrhea all the time.

They weren't writing about stepwise fever and relative radicardia in the Everest Pirates. I'm shocked. I'm shocked. I don't believe that they were. I don't believe so. So anyway, so it wasn't explicitly described by a lot of ancient Greek or Roman physicians. Okay. But, I mean, undoubtedly, it was around.

Right. For centuries, its name, typhoid. was used to describe more a set of symptoms rather than a separate disease. Typhoid actually means, it just means typhus-like. Huh. Interesting. Yeah. And I just want to give a little bonus factoid, even though we're going to cover typhus at some point in the future, because that's another big, that's another big like season one era kind of TPWKY. I'm just going to tell you the etymology of typhus now because to say, oh,

it's typhus-like and then move. move on and then leave it. Yeah. Basically, typhist comes from the Greek typhos, meaning stupor caused by fever. And it's also related to smoke or mist or fog, referring to the brain fog that's associated with typhus and occasionally with typhoid. Okay. So because of its similarity to other GI illnesses, it's hard to pinpoint specific typhoid

epidemics or estimate it's an impact separate from other illnesses caused by poor sanitation or clean water infrastructure. But that doesn't mean people won't try to ascribe typhoid as causes of epidemics in history. That's my favorite thing. For instance, Alexander the Great may have died of typhoid at the age of 32. What? Yeah, he was only 32. He was only 32?

I know. Oh, I know. It also could have been, I will note, poisoning malaria, brucilosis, etc. Mm-hmm. Okay. And typhoid has also been blamed for the plague of Athens, which happened in 430 BCE during the Peloponnesian War between Athens and Sparta. Okay. This epidemic, the plague of Athens, killed approximately one-third to two-third of the population of Athens, including the leader, Pericles, and about one-fourth of the army, basically sealing the fate of Athens.

Hmm. But was it actually typhoid? Probably not. And the reason that people think it was is because there was an article reporting salmonella interica genetic material in ancient DNA samples of likely victims. But those findings have been highly criticized. Smallpox, typhus, and measles are also decent contenders with, of course, the possibility that it was a totally different pathogen that's no longer circulating. Right. Yeah.

But what is definitely true, again, is that typhoid was an infamous killer during wartime or times of unrest, primarily because of poor hygiene and a lack of clean water made transmission easy, as you heard in the first hand snippets. And add on to that a lack of knowledge about germ theory and how the disease is transmitted and you have a recipe for disaster. In the Jamestown colony, typhoid was responsible for wiping out an estimated 6,500 of 7,500 colonists in the early 1600s. Oh, yeah, a lot. I mean, you know, they weren't, they also weren't in the best, like, they weren't in the best health otherwise. Right, that's the thing. I mean, yeah. Mm-hmm.

I mean, it was sort of like, it was a, what had it? they call it in some of these descriptions it was like a seasoning, like you had to get there. And it was like you had to go through this hazing of a disease, like the seasoning of a disease. Like, I don't know how else to say it, but you either survived or you didn't. Right. Yeah. I mean, that was like all of childhood for so long. For so many thousands of years.

Yep. Yeah. Population growth in the major cities during the industrial age way outpays. way outpace the infrastructure or knowledge or technology to manage the waste that was being produced. And this is reflected in the annual incidence of typhoid in Europe during this period, which was about one in 200 people. Wow. It's really high. That's really high. Yeah. Albert, Prince Consort of Queen Victoria, died in 1861 of probably typhoid. Oh. And President William Henry Harrison, who was the ninth and shortest serving U.S. president died from what was likely typhoid just 31 days after taking office.

It was also a terrible person. He was. He was. The 12th U.S. president, Zachary Tyler, may also have died from typhoid. And three of Louis Pasteur's five children died from typhoid fever, apparently. Oh. Yeah. So this was an enormously feared.

disease, and it was one that did not respect divisions of class or wealth. Starting in the 18th century, physicians began to observe or describe that typhoid and typhus were two different diseases. Several physicians noted the difference in fever intensity or duration or cyclicity, etc. or noted the lesions in the pyres patches of the small intestine. Confusion lingered, though, especially in a diagnosis of non-finald, fatal cases of typhoid. In 1837, two Philadelphia physicians, William Gerhard and Caspar-Pennock, published their observations that typhoid and typhus were distinct diseases. An epidemic of typhus in 1836 allowed them to note not only how the diseases behave differently,

so typhus was more likely to cause an epidemic and much less likely to appear in sporadic cases, as well as how their pathophysiology differed. But there was still a major piece of the puzzle missing. How was typhoid fever transmitted? Yeah. At this time, which was the first half of the 19th century, germ theory had not yet been developed, although the concept of contagion was well established.

I feel like that's what makes it so classic TPWKY, Like getting to talk about nobody knew germ theory and then we learned about germ theory, you know? That's like very classic. It is. It is. I feel like also I'm like, I hope people aren't sick of hearing about like the era of germ theory. And like it just is such a mind blowing like the revolution of awareness of the world around us is so wild to me. It is just like you talked about in the Gyardia episode when Van Lue and Hook looked through his microscope and saw the

whole world in the water. Like, it is, it is mind-blowing and phenomenal to think about the time of that shift in mindset. It is absolutely fascinating. Good. Well, I'm glad you're not sick of it because I'm not sick of it either. And we make the rules around here, so. So, yeah, so people knew maybe not about microbes, but they knew about contagion in that concept. And the English physician William Budd, and I highly recommend you check out his Wikipedia page just so you can see his incredible facial hair. He discovered the link between typhoid and fecal oral water contamination after tracing one outbreak of the disease in a village in 1847 and finding that the only link between the households was that they shared a well. And then later, like years later, after learning about John Snow's work between cholera and the Broad Street Pump, he became even more convinced that contaminated water was the source of typhoid outbreaks. I was just about to ask, what time was this in relation to John Snow and cholera? I love it.

And just like with cholera, there may have been some resistance in accepting that water, not bad air, could be the cause of so much illness and death. But if there was resistance in the face of typhoid fever and transmission, it was fairly short-lived. As I mentioned, the massive global population growth had led to an equally massive waste problem. In London in July, in August of 1858, for instance, I mean, you heard the first hand of cholera. It's pretty, like, memorable. The poop and trash in the River 10. baking in the summer sun led to such an overwhelming foul smell that it was called the Great Stink.

There's an entire Wikipedia page about it. And I really, I just want to read this. This is just an episode of growth stuff. So I wanted to read this excerpt from a contemporary newspaper about the Great Stink. Yes. Quote, for the first time in the history of man, the sewage of nearly three million people had been brought to seeth and ferment under a burning sun in one vast open cloaca lying in their midst. I can't say.

Oh, my God. I have to try that again. I can't say open cloaca without a, without laughing. Uh-uh. Open cloaca. Oh, dear. In one vast open cloaca lying in their midst. The result, we all know, stench so foul we may believe, had never before ascended to pollute the lower air.

Never before, at least, had a stink risen to the height of a historic event. Do you see why I needed to read that? Yes, 100%. I agree with it. It was the correct decision. Yeah, so check out the Wikipedia page. 1858. Yep. What a time.

Events like the Great Stink and the cholera epidemics finally forced public officials to recognize contaminated water was a public health issue. And this was only deepened with the development of germ theory. Side note, the Chicago River was reversed to try to control the outbreaks of typhoid and cholera. Wow. Isn't that cool? Okay. So hopefully by now, I have painted somewhat of a picture of the prominence or infamy of typhoid through the 1800s

so that you can understand why isolating the causative agent became a top priority for so many bacteriologists. Yeah, definitely. And because of its prevalence and popularity in research, it's a bit tough to establish priority on who first discovered the bacterium. One likely suspect was the Polish scientist, oh boy, Taduz. Browitz, who described rod-shaped bacteria in the organs of people infected with typhoid. And he even isolated and cultureed the bacteria, but he never followed through by trying to

determine whether those cells were responsible for the disease itself. Got it. You never did all of the postulates. Right. Credit is usually given to German pathologist Carl Eberth for first isolation. And this is reflected in the fact that the first name given to the bacterium was, was Eberthella. Eberthella. Okay. The rest of the late 1800s and early 1900s was a busy and productive time for typhoid researchers.

The development of the Wydel test allowed physicians to test for the typhoid bacterium. Basically, you take serum from a suspected patient and see how it reacts when exposed to a culture of the bacteria. If a precipitate forms, you've got typhoid. And then the vaccine was next, just like with a discovery and description. of the typhoid bacterium itself, there seems to be some debate over who first created the

typhoid vaccine. Many different people at least had a hand in it. Credit usually goes to Sir Almoroth Wright, who was an English pathologist, and he began testing an early typhoid vaccine on army officers in the Indian Medical Service. Not for effectiveness against typhoid, though, but rather to see whether calcium chloride prevented hemorrhaging in those injected. What? As like an additive or a stabilizer. So he made a whole new vaccine and was like, I'm not testing this vaccine. I just want to test the adjuvant.

I don't get it. But he usually gets credited for the first typhoid vaccine, even if many others paved the way for him. And he followed up his first tiny test with more extensive testing. this time to actually observe the efficacy of the vaccine in protecting against disease. Oh, what a concept. What a concept. But instead of exposing the participants to typhoid, which was, as we know, a method still occasionally practiced, like, you know, actual challenge or whatever, he tested the serum of those vaccinated to see whether typhoid bacteria would agglutinate.

So kind of smart. Yeah. Pretty smart. And sure enough, the serum of those vaccinated did seem to agglutinate bacteria, but did that translate into actual protection in the body? Right. The bacteria in the precipitates were still viable, after all. So they did the unethical thing and exposed one of the participants to typhoid. And fortunately, he did not get it.

The development of a typhoid vaccine completely changed war. Oh. Yeah. I've talked before on the podcast about just how much death and illness during war comes from infection rather than combat. But I didn't realize just how much typhoid was often responsible for the most damage. Yeah. I don't think I would have put that together necessarily. Yeah. I mean, and it makes sense given like the conditions of, you know, living and so on and like, how do you prepare food in a clean way? How do you poop in a clean way?

Like, how do you clean yourself in a clean way? Yeah. Yeah. During the American Civil War, for instance, 80,000 of the 2 million soldiers in a Union Army, there were no good records for the Confederate Army, got typhoid, about 5%. Wow. Yeah. And in the Spanish-American War, which is where the firsthand accounts came from,

approximately 21,000 troops were infected with typhoid and nearly 1600 died. Wow. Yeah. That's a lot. Most of the time, typhoid killed more soldiers than direct combat. Yeah, I feel like that's a theme that we often come back to. It is. It's not funny.

It's awful. World War I would be the first major conflict in which typhoid did not contribute enormously to the death toll. Because of the vaccine. Because of the vaccine. Because of the vaccine. In previous wars, the attack rate of typhoid was estimated to be one in five, but that dropped to one in 2000 by World War I due to the vaccine and improvements in sanitation practices. What? That's bonkers.

I know. Yep. It's pretty clear. That's a phenomenal. Wow. Wow. Huge. Huge. Wow. All right. Here we are in the early 1900s. We're finally here. We're finally here.

I just want to set the stage a bit for this next part of the story of typhoid. Yes. So typhoid has been a common place but still very much feared disease for the past centuries. And while there have been some major developments in understanding its transmission and pathophysiology, both sanitation infrastructure. and medical treatments lag behind, so the threat remains. A doctor can diagnose a case, but they can't treat it because antibiotics haven't been discovered yet. A typhoid vaccine did exist, but they were new and not trusted and generally reserved for the military. Right, yeah. And cities began to grow at incredible rates. All that

poop with nowhere to go. Oh, oh. Enter Mary Mallon. Mary Malin emigrated to the U.S. from Ireland in 1883 at the age of 15 and began working as a cook. Okay. And she seemed to be really good at it. She seemed to be in steady employment in the New York City area with short-term contracts working for wealthy families from season to season. And that was like a normal thing for a lot of cooks, just like contract work. Right. Mary's life continued in this rhythm for 20 and some years until the events that would turn her

from Mary Malin to the infamous typhoid Mary. So she was like in her late 30s, like mid to late 30s? Yes. In 1906, an outbreak of typhoid occurred among the household of the wealthy New York City banker Charles Henry Warren, who was renting a summer home in Oyster Bay in New York. Two of his daughters, his wife, two maids, and the gardener all became sick. isolated outbreaks like this did happen from time to time, but this was still a huge cause for concern, not just because the disease could be fatal, but because an outbreak of typhoid could tarnish a home's reputation for years because it suggested that the water lines weren't clean. I'm scoffing my face in that part. I know. It was a very good scoff face. I wish that I had taken like a screenshot of it or something.

So the owners of the house were desperate to trace where the outbreak originated. I mean, okay. Yeah. I mean, it makes sense. Like, you want to know, like, okay, if we can put a stop to this, let's put a stop to this. Yes, of course. And it is very deadly in that. But like the reputation thing, like.

Well, I mean, they were like, but we need to make sure to rent our H-E-I-R-B-N-B. Our Airbnb. Airbnb. I'm pretty sure I stole that joke from The Good Place. It's a good one, though. Yeah. Okay. Anyway, so these owners hired George Soper, a sanitary engineer.

Okay, cool. His job was basically a mix of health inspection and shoe leather epidemiology. Awesome. Yeah. And he went around the entire property on Oyster Bay, looking to see whether the toilet waste ran into the water, sources or if the local oysters from Oyster Bay were contaminated. All right.

And he found nothing. Okay. But the typhoid had to come from somewhere, and the source had to be unique to that household since no other cases were detected in the nearby town. Soper learned that the family had hired a new cook just before the outbreak started. That cook's name was Mary. Mary Malon. At first, it may have been hard to see how a cook could be the source of a typhoid outbreak

since the bacteria would be killed during the heating process. But then it was revealed that one of Mary's most popular dishes was ice cream and fresh peaches. Boom. How sad. Like, what a great. That sounds like such a good dessert. I mean, we probably should have made a quarantini that was like peach and ice cream themed. We totally should have.

like bloody typhoid Mary, what else were we going to do that? Come on. Also, the other thing is that where can you get peaches in November? In this hemisphere, you cannot. So we couldn't have taken a photo. It would be sad peaches, for sure. Very sad. Yeah. So, yeah. Yeah. Well, but as you can imagine, ice cream and peaches, there's not a whole lot of heat inactivation. No, not happen. And during the time that Soper was investigating the source of this outbreak, the existence of typhoid. carriers had been hypothesized and observed, but it was not like a super widely known concept. Interesting. Yeah.

Nevertheless, Soper became convinced that Mary was the one to blame. But there was one major problem because Mary had already moved on. She had gotten a new job and had left no forwarding address. So Soper set to investigating her past employment to see whether she was, linked to any other typhoid outbreaks. He became a bit obsessed because he essentially thought, okay, if I can show that she is the cause of all of these cases, then that's my career made, boom, done. Huh.

Like it was his ticket to fame. So, anyway. Okay. But what he found was that in seven of the eight families that Mary had worked for over the years, there had been a typhoid outbreak during or right after her employment. Wow. Yeah. seven of the eight. And Soper finally caught up to her in 1907 amidst another typhoid outbreak in the family that she was cooking for.

Okay. And this one resulted in the first death definitively linked to Mary. It was the daughter of that family. Unfortunately, Mary didn't write or talk extensively about what happened from her perspective. So we have to rely on the words of contemporary sources, including George Soper. He wrote his account of events in which he and most subsequent retellings, including this one, he framed it like a detective story with Mary as the villain at the center of it. Right. In 1907, when Soper tracked down Mary's current place of employment and learned of the typhoid outbreak currently occurring, he essentially stormed right in, pointed a finger at her, and loudly accused her of making everyone around her sick with her unclean habits and carelessness. Like that's how he just walked in out of nowhere off this street.

And it was like, you're filthy and killing people with your poop pants. Yeah. You're the cause. Like, you're the reason people are dying. Jeez. And then, and then he was like, and you know what? I need a poop sample from you right now. Good luck, buddy.

And so Mary was like, um, excuse me? And he also, so after demanding this fecal sample, It's not like he was like, oh, this is how it might work. This is what a typhoid carrier is. Right. Listen, we know that you didn't mean any harm. Like, we're just trying to get to the root of this. There was no humanity is what I feel like you're saying in his response.

Like there was no humanity whatsoever. Absolutely not. And Mary was like, excuse me? Excuse me? And so she grabbed a carving fork, according to Soper, and charged him. and charged him, so he ran away. He ran away. Yeah.

Oh, my gracious. But Soper didn't give up. Instead, he found out where she lived, and she was living as an unmarried woman with a disreputable boyfriend and a big dog, which Soper felt important to note, a big stinky dog, which, like, is probably a really cute dog. Yeah, I bet it was, like, shaggy and drooly and nice. Oh, that sounds sweet. And so he went to where she lived and tried to get a fecal sample from her and then tried to befriend the boyfriend to try to be like, let's trick Mary into giving a fecal. Like, what? What is this dude's damage, man?

I don't know. I don't know. And every time Mary just shut down, crossed her arms, and was like, leave. Yeah. She just sent him packing every single time. It makes sense, right? And eventually, though, he got the New York City Health Department involved. including a Dr. Sarah Josephine Baker, who was a huge figure in infant and maternal health.

And so she was sent to try to reason with Mary more calmly. Instead, Mary ran away and hid for hours. But eventually her hiding place was found out, and she was dragged, literally kicking and screaming to the hospital, where she would be forced to provide samples. sure enough, she was teeming with a typhoid bacteria. Do you have a number on that, Erin? I'm sorry, Aaron. Let me just Google that real quick. We don't 100% know, but...

Okay. So, but yeah. So she was the first carrier described. Like known definitive carrier. Yeah. So because she was considered a flight risk, she was held in the hospital and then moved to North Brother Island, where there was a hospital that started out as a smallpox isolation building, but then turned into any disease we choose isolation building. So like tuberculosis, leprosy, etc. And Soper tried to convince Mary to have her gallbladder removed, even though, A, a surgery in the early 1900s was like super dangerous. Yeah, almost certainly death. Like no antibiotics. And B, its removal, like you said, was no guarantee that she would then be typhoid free. And so, but she was like, no, I don't want that. And so then he was like, all right, well, then I'm going to write a book about you and I'll split the profits with you if you promise to stop cooking.

And she was like, no, she basically like just refused to talk to him. And she remained in isolation and her fecal samples were regularly checked for the presence of the bacteria, which were found more often than not, although there were some negative days. In 1909, so that's two years and three months after she was first isolated, she filed a lawsuit for her release, saying that her imprisonment was unlawful and stripped her of her civil liberties. And it was at this time that the term typhoid Mary, coined in 1908 at the annual meeting of the American Medical Association, like when they presented her carrier status. This term reached the general public. Overall, the tone of the articles were very sympathetic to Mary. Her imprisonment to the general public was seen as a violation of civil rights and prejudice against a poor immigrant woman. But this case took place at a time when courts tended to rule in favor of social protections rather than individual rights.

Interesting. For instance, just a few years before, in the 1905 decision Jacobson v. Massachusetts, the Supreme Court unanimously ruled that required smallpox vaccination did not violate individual rights. Quote, the liberty secured by the Constitution does not import an absolute right in each person to be at all times. and in all circumstances wholly freed from restraint. Basically, the ruling was that if by exerting your own individual rights, you are impinging on the rights or health of others, then no, you cannot do that. Those are not rights.

That's how it's always been. And so Mary lost the suit and continued to be held in the custody of the Board of Health of the City of New York. But not for very long. The following year, in 1910, she was released, least on the condition that she promised not to work as a cook anymore and to report back to be tested. She agreed to the terms and then promptly disappeared and never went back for checkups. She was rediscovered in 1915. Soper had resumed his work as a sanitary engineer and was

in the process of investigating an outbreak of typhoid at Sloan maternity hospital. Oh, no. When he learned that some of the staff referred to a typhoid Mary Cook who seemed to link to the outbreak. He was like, this is, are you serious? Like, this, is this, who am I going to find? Am I actually going to find Typhoid Mary? Am I going to find Mary Malon? And it was. But Mary Malon had been going by a different name. Turned out, Mary had not upheld her end of the deal and continued to seek out employment as a cook, which was likely the only profession that she had any skill or experience in. Since her 1909 case had put her name out there and gained her some notoriety, she couldn't use her real name to get employment. Right.

And when Mary was apprehended the second time, she did not receive the same level of public sympathy. The New York City Health Department placed her in forceful isolation again on North Brother Island in the East River, where she would live out the rest of her days. Over 20 years, never admitting or acknowledging her role as carrier. She did have a few friends on the island and apparently a little fox terrier. And she worked a bit in the bacteriology lab, but she never felt she belonged on North Brother Island and felt that her freedom had been taken away unfairly. She died at the age of 69 on November 11, 1938 of pneumonia following a stroke. In total, Mary was linked to 53 cases and three deaths, although it's possible that the actual numbers were higher. The impact that Mary Malin had on the world goes way beyond the people she infected.

Yep. And I had a hard time putting all of my thoughts and feelings about Mary Malin and typhoid Mary into one coherent thesis. So I decided to make a list of the different themes or lessons or whatever of the story. The first theme was probably. probably also the earliest and the simplest. Just medical mystery, epidemiological detective work, a who done it. Right? Boom.

That's one story that people use. Number two, the concept of a super spreader. The term typhoid Mary was in popular use even before this pandemic. And so, like, you know, even before we use it as someone who unknowingly or knowingly infected a bunch of people with something. without seeming like they were sick or anything like that. Exactly. Number three, discrimination and oppression.

Mary belonged to a few groups that have been historically very much discriminated against here in the U.S. Mary was poor. She was an immigrant, and she was an unmarried woman who did not fit the contemporary standards of femininity. In Soper's words, quote, those who knew her best in the long years of her custody said, Mary walked more like a man than a woman and that her mind had a distinctly masculine character. Like, okay, George. Okay, buddy. And Mary Mallon wasn't the only typhoid carrier in New York City.

Definitely not. In the years after she was imprisoned, at least 50 additional carriers had been identified, and one estimate from 1919 put New York City as having over 25,000 typhoid carriers. What? Some who had been identified became repeat offenders like Mary, but no one, none of them, faced a similar lifetime imprisonment. What? Most of them were given alternative jobs or means for providing for their family. But Mary wasn't considered a breadwinner because she had no family.

Because she was just a single woman in their eyes. Mm-hmm. Maybe she was put on an island to serve as an example. But although Mary's punishment may have been so extreme because of who she was or what she represented, the unavoidable fact that I keep coming back to is that her actions, particularly her deliberate choice to keep working as a cook, directly caused the illnesses and deaths in others. Which brings me to theme number four, and the one I think has the most relevance for today, that of the tension between individual rights and public health.

Was Mary's imprisonment too harsh or biased? I mean, yes, I think we can agree. We can all agree that, yeah, it was. But should measures have been put into place that would have prevented her from making others sick? Yes. Yes. Without a doubt. Yes.

In any society, there is no such thing as absolute freedom. There is a limit. If by exerting your own individual rights you are, impinging on the right or health of others, then that freedom is not something owed to you. This is part of the social contract, the agreement that we all make that by living in and benefiting from a society, we have to give up some of our individual freedoms. This can be a tough balance to strike, particularly in the realm of public health. There's a quote from one of the books I read about typhoid Mary.

quote. But first, Erin, I just want to say you said that really beautifully. Like, I absolutely loved it. I feel very strongly about this. It was, I mean, I feel 100% exactly the same way, but just the way that you worded that was perfect. Thank you. That makes me feel nice. Okay. Here's the quote. Yeah. On the one hand is the commitment to protect the public's health. On the other is the fear of arbitrary power and the loss of individual freedoms. So that's from Judith Leavitt. Mandatory vaccinations, forced quarantines, public identification of so-called patient zeros, and in the context of COVID-19, mask mandates.

These are all areas in which there has been ample discussion of individual freedoms being trampled upon, some of which may be justified. others definitely not. Like masks. Let's not mistake inconvenience for oppression. Oh, snap. Being imprisoned on an island for decades because you are an asymptomatic carrier of typhoid. Yeah, okay, maybe there's a touch of oppression there.

Having to wear a mask to pop into the grocery store for 15 minutes, that's not oppression, period. Not oppression. End of story, not oppression. It's not oppression. So what can we learn from Mary Malin's experience? Oh, good question. As I was reading about the story of Mary Malin, one thing that stuck out to me was how much pain and suffering, both for Mary and for the people that she infected, could have been prevented through simple communication. Yeah. Her doctors, the New York City Health Department, they could have taken the time to talk with her, not down to her, about the science behind typhoid fever, mission, and they could have explained in a non-judgmental way how she could transmit unintentionally the bacterium to those around her.

And then, maybe they could have given her more opportunities or training to find employment in a different area. Maybe then she wouldn't have felt like she needed to lie to continue to cook. Yeah. We as a society have the knowledge and the platforms to communicate accurate scientific information. And when that information has the... power to save people's lives and prevent misery and suffering, leaders have a responsibility

to communicate that information without their own political agenda. And accurately. Yep. The disinformation and mistrust in science spread by Donald Trump and other members of the Republican Party during this pandemic and other world leaders, I should know, like, you know, a lot. Or so far. It's not, you know. Boris Johnson, it's fine.

I was a nice for you now. I'm fine. This has already done incalculable damage. How many deaths, how much misery, how much suffering could have been prevented by communicating science rather than sowing hatred and fear? History is full of lessons like this. And, you know, there's that saying that's like those who cannot learn from history are doomed to repeat it. But like, I mean, yes, that's true. but I think what might be, you know, an addendum should be, and those that do learn history

are just doomed to watch others repeat it. We can always do better, but it feels like we rarely actually do. Well, it also might be that people are taking the wrong lessons from history or learning the wrong parts of history. That's definitely true. We did a great job. We isolated Mary on an island and kept her there forever. Like, you know, I don't know.

It's a much more nuanced story than that. Like, let's learn the nuance. I feel like that's important. Like, yes, it was unfair, but yes, she also killed people. So what can we do differently? Like, that's what we should be asking ourselves. And we have the opportunity now. So like, yeah.

But yeah, I've gone on way too long already. So I'll just wrap up the history by saying that with improved sanitation and clean water infrastructure, combined with the development of chloramphenicol in 1948, typhoid, like really dropped. in the second half of the 20th century in most developed countries. However. However. It has continued to cause enormous outbreaks, which some of these outbreaks leading to over 100,000 deaths in many other parts of the world, and the emergence of drug

resistance strains might pose an additional threat. But, Erin, I'm going to let you take it from here. Oh, great. Love to pick it up on such a happy note. Oh, boy, I'm sorry. I'm sorry. Let's take a quick break before we jump in. So I already said this, but I'll just repeat it. We do not have good data on the incidence of typhoid fever globally. There's really big ranges. One of the biggest papers that estimated typhoid disease burden was all the way back in 2004, and that estimated over 21 million cases annually.

and that one also estimated an overall fatality rate of about 1%, which would mean over 200,000 deaths annually globally. Oh, my. So that was a 2004 estimate. Another paper from 2012 estimated 13.5 million cases annually. So if you look at the World Health Organization, they say somewhere between 11, to 21 million people becoming sick with typhoid fever every year worldwide. And they estimate between 128 and 161,000 people dying every year. Wow. Worldwide. I mean, I, yeah. If that's not

depressing enough. Okay, here we go. Like I mentioned earlier, typhoid is largely a disease of children in places where it's endemic. So Pakistan is one place that I'm going to talk a lot about because there's some very good things happening in Pakistan right now. But 63% of cases and 80% of deaths related to typhoid were among children under the age of 15, for example. Oh, my God. Yeah.

So it's really, really awful. In the U.S., just for sort of local coverage, the U.S. estimates over 5,700 cases of typhoid in the U.S. every year, although we only actually diagnose about 350 cases, which I think is really interesting. Huh. So that's like part of how we have such a huge discrepancy where we only diagnose this many, and then we have to estimate that that's like less than 10% of the total number of cases we think there actually are.

Now, like you mentioned, Aaron, antibiotic resistance is. is a massive problem for salmonella typhi, as it is for most bacteria that we talk about. Oh, boy. But another time I'll talk about Pakistan, another depressing one before we get to the good news. Since 2016, Pakistan has been in the midst of an extensively drug-resistant typhoid epidemic. Right. Since 2016, between 2016 and 2019, over 10,000 people had been infected with a strain that is resistant to all but one. oral antibiotic.

Oh my gosh. And it's not just there. I mean, typhoid is a global disease. It's in, I think, basically every country, right? Like, it's across the whole globe. And antibiotic resistance has been documented across the globe. So let's end with some slightly good news, shall we? That sounds great.

In 2017, the World Health Organization pre-qualified a new, new vaccine. And this is an exciting one. If you remember from our vaccines episode, which if you want to go back and listen, you can do that, but I'm going to explain it anyways, so you don't have to. There's a bunch of different types of vaccines. And I mentioned that the vaccines that we already have for typhoid are a polysaccharide, which is just a sugar, or we have a live attenuated vaccine, but you can't give that to small children. So a, a very important. So a very succoride. A polysaccharide, which is just a sugar. So a better type of vaccine would be a conjugate vaccine, which is when you take a polysaccharide, which is a sugar, and you link it to a peptide or a protein. Because the proteins are what actually allow for our body to make a stronger and more long-lasting immune response.

So in 2017, the World Health Organization pre-qualified a conjugate vaccine. That's very exciting. It's very exciting. Yes, it is. And so it's a very promising vaccine. That was just a pre-qualification. Recent data from a phase three clinical trial that's going on in Nepal shows that it's very effective at inducing an immune response. And it reduced salmonella typhi infection across the study period.

And this study was done in children, age nine months to 16 years. So that means this is a vaccine. that will be able to be given to children. It's already being given to children. And it's effective. That's amazing. Yes. Now, even though this is a vaccine that's still undergoing investigation,

so we're still in like the last phase of trials, typhoid is such a huge problem and especially these antibiotic resistance strains, there's been enough studies of the safety of this vaccine that starting in 2019, this vaccine has been introduced into routine immunization in some countries, including Pakistan. This is like what's ongoing right now is that kids now are like starting, are getting this vaccine. So hopefully, yeah, in the next year, two years, three years, we should really see a drop in typhoid. That's awesome. Isn't it?

It's really, like, that's incredible. to finally have a vaccine that's long-lasting, that's effective, and that can be given to children so that we can really protect the most vulnerable groups. Like, that's incredible, especially as it becomes more widely available. That's my good news, Erin. Oh, good. I loved it. So that's, I think, the story of typhoid. That's a, it's a long story? Pretty long. Not our longest. Not our longest. A good start to this season, though, I think.

It feels good. It feels, yeah. I am, I'm looking forward to all of the diseases that we're going to be covering this season. We have a few fun ones lined up already, including spoilers, a crossover. Oh, yes. The crossover is going to be good. I am very excited about it. So normally last season, when we did our COVID-Evel, episodes, those were entirely separate. We talked a little bit about it today because you can't not, right? Yeah. Not when you're talking about typhoid Mary now. Right. But from this point forward, we will, as last season, have our COVID episodes be separate from our regular episodes. So there won't be a ton of COVID talk in our normal episodes if you're like, don't want to listen to it or whatever. Right. Yeah. So, but yeah, it's, this wasn't, this was a very important. episode, I think, to do in this climate.

Oh, boy. Well, sources. Okay. I've got a few books I can shout out. So one by Adler and Mara called Typhoid Fever History. Judith Leavitt, who wrote Typhoid Fever, captive to the public's health. And also, did you know that Anthony Bourdain? wrote a book about typhoid Mary?

Stop. Anthony Bourdain? Like Anthony Bourdain? Yeah. What? Yeah. So I read that one too. Oh, because she was a cook.

Yeah, she was a cook. Oh, okay. It was an interesting one. And then I will shout out a few papers that were super helpful. So there was a couple papers by V.J. Cirillo that were actually like really interesting. And then also by Priscilla Wald, Typhoid Mary and the science of social control. I have actually like a lot of different papers for this one. So just check it out on our website. I don't want to spend the next five minutes reading them. I had a few different papers on the kind of

mechanisms of typhoid and the clinical disease. If you want to know more about the carrier state, that paper is by Gonzalez Escobedo et al in Nature Reviews Microbiology. And then the papers and information about the new vaccine. All of that will be on our website. This Podcast Will Kill You.com under the episodes tab where you can find the sources for this episode and every episode we've ever done 61. This is number 61. 61. Wow. Of our normal season episodes. Yes. We've done more like COVID, but yeah. Well, thank you to Bloodmobile for providing the music for this episode and all of our episodes. Big time shout out to Georgia Hard Stark for introducing us with typhoid. So many.

years ago. Yes. Thank you to also everyone at the Exactly Right Network who make this podcast possible. Definitely big time. Thank you. Thank you. And thank you to you listeners for listening. It's honestly like we're honored. We can't believe people want to listen, but we love it. A literal dream. A literal dream that we didn't even know that we had and now we can't stop dreaming it. And it's the greatest. It's basically what it feels like. Well, until next time, wash your hands. You filthy animals. And literally just wear a mask. Please wear a mask. I'm Amanda Knox. And in the new podcast, Doubt the case of Lucy Letby, we unpack the story of an unimaginable tragedy that gripped the UK in 2023. But what if we didn't get the whole story? Evidence has been made to fit. The moment you look at the whole picture,

the case collapsed. What if the truth? was disguised by a story we chose to believe. Oh my God, I think she might be innocent. Listen to Doubt, the case of Lucy Letby, on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts. This is Special Agent Regal, Special Agent Bradley Hall. In 2018, the FBI took down a ring of spies working for China's Ministry of State Security, one of the most mysterious intelligence agencies in the world.

The Sixth Bureau podcast is a story of the inner workings of the MSS. and how one man's ambition and mistakes opened its fault of secrets. Listen to the Sixth Bureau on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. I'm Clayton Eckerd. In 2022, I was the lead of ABC's The Bachelor. But here's the thing. Bachelor fans hated him. If I could press a button and rewind it all I would. That's when his life took a disturbing turn. A one-night stand would end in a courtroom. The media is here.

This case has gone viral. The dating contract. Agree to date me, but I'm also suing you. This is unlike anything I've ever seen before. I'm Stephanie Young. Listen to Love Trapped on the Iheart Radio app, Apple Podcasts, or wherever you get your podcasts.