This Podcast Will Kill You - Ep 86 Typhus: Another lousy episode

Episode Date: December 14, 2021

We’re back with our first episode of Season 5, and we’re starting off with a bang! Epidemic typhus, that friend of war and famine, may have caused more wartime deaths than all battles combined, and though it may seem like a disease relegated to the past, typhus only needs a minor disruption to turn it into a scourge of the present. In this epic season opener, we turn our sights to the louse-transmitted Rickettsia prowazekii, first diving into the strange and terrible biology of this bacterium before exploring the deep history of this tiny but mighty pathogen. The vast story of typhus takes us on a journey on a ‘coffin ship’ of the Great Irish Famine, through musings of the origins of human body and head lice, to German-occupied Poland during WWII with tales of vaccine sabotage and lice feeding, and finally to the present day, where we discuss the very real threat that epidemic typhus continues to pose. Check out this episode for all you ever wanted to know about epidemic typhus and more! See omnystudio.com/listener for privacy information.

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unceasing in her attention to him. The day was exceeding. exceedingly hot and sultry, and I could not have remained on deck, but the captain spread an awning over it, which kept the cabin cool. We lay at some distance from the island, the distant view of which was exceedingly beautiful. At the far end were rows of white tents and marquise, resembling the encampment of an army. Somewhat nearer was the little fort, and residents of the superintendent physician, and nearer still the chapel, Siemens Hospital, and little village, with its wharf and a few sailboats. the most adjacent extremity being rugged rocks, among which grew beautiful fir trees. At high water, this portion was detached from the main island and formed a most picturesque islet. But this scene of natural beauty was sadly deformed by the dismal display of human suffering that it presented.

Helpless creatures being carried by sailors over the rocks on their way to the hospital, boats arriving with patients, some of whom died in their transmission from their ships. Another and still more awful sight was a continuous line of boats, each carrying its freight of dead to the burial ground and forming an endless funeral procession. Some had several corpses, so tied up in canvas that the stiff, sharp outline of death was easily traceable. Others had rude coffins, constructed by the sailors from the boards of their births, or should I say, in a few a solitary mourner attended the remains, but the majority contained no living beings save the rowers. I could not remove my eyes until boat after boat was hid by the projecting point of the island, round which they steered their bloomy way. From one ship, a boat proceeded

four times during the day, each time laden with a cargo of dead. I ventured to count the number of boats that passed, but had to give up the sickening task. Oh, my goodness. Yeah. So that is from a diary that somebody published called Famine Ship Diary, the Journey of a Coffin Ship. And it's written by someone named Robert White, but that's a pseudonym. And it tells the story of Gross Isle, which is a place in Canada where a lot of ships sailed to from Ireland during the famine. And typhus was absolutely out of control, like,

in Ireland, on the ships. And it's estimated that more than 20,000 people died from 1847 to 1848 on these so-called coffin ships and also in Canada when they landed. And a lot of people who died were mostly people coming from Ireland, but also like the doctors and the priests, and clergyman or so on who attended them. So, yeah, it's really, like, heartbreaking. God, that's awful, Erin. Yeah. Hi, I'm Erin Welsh.

And I'm Aaron Alman Updike. And this is, this podcast will kill you. Welcome. We're starting strong, clearly, to our fifth season. Yeah, this is episode. 86 of yeah which marks the beginning of our fifth season feels like it was just yesterday that we recorded alcohol it was it kind of was but we're excited to be back and we're excited to do this episode this topic I mean this is a this is a big one it almost rightly belongs in like our

first season I think it was a strong first season contender and it's just taken us for extra seasons to get here. It's going to be a very interesting episode, I think. I think so too. I gained a new appreciation for lice. I can't wait to talk about lice in like more detail than people want. I know. Lice are so fascinating. I think this just like goes to show that we got our PhDs in the right fields. I was thinking the same thing. We are true vector-borne disease ecologists of heart, I think. We really are. Yeah. Okay, so, Erin. Yes.

What time is it? It is quarantine time. It is. And what are we drinking this week? This week we're drinking the Saust Laos. The Saust Laos. I love it. And in the Saust Laos is basically, it's like a, you know, a bourbon eggnog.

Yeah. You can do rum if you want. I'm going to do bourbon. And I've never made eggnog before in my life. Like I've only ever just gotten it from the store. But I made it for the first time. And it is really delicious. I've never had eggnog that I've enjoyed.

So I would like to try your eggnog, please. Okay. But yeah, part of the reason that I wanted to do an eggnog for this is because Harold Cox, I think, was his name, was a researcher at Rocky Mountain Labs in Hamilton, Montana, which we talked about in our Rocky Mountain Spot of Vever episode. And he developed a typhus vaccine in egg yolks. And so I thought, you know what, let's do an eggnog. And also, like, this episode's supposed to come out, December. So perfect. Feels like a good seasonal Bev. So we'll post the full recipe for that quarantini, as well as the non-alcoholic version, our placebo-rida,

our website, this podcast will kill you.com and all of our social media channels. We will. And I just want to add that don't feel compelled to homemake eggnog. And there are tons of options out there at the store and there are tons of non-dairy options and vegan options as well. So take your pick, really. It works with it all. Everyone can enjoy an eggish nog. Yeah, eggish knob. Okay. Other podcast business. As always, this podcast will kill you.com is our website, and it's pretty great. You should check it out. We have links to our Goodreads list and our bookshop.org affiliate account. We have links to Bloodmobile, our music, who's also on Spotify.

We've got links to our Patreon. We've got merch. So much cool merch. Did you get your holiday gifts yet? Erin, what am I missing? I honestly, I don't know. I'm just glad that you went through so many of them that I wasn't even. I was like, she's got it. got it covered totally. Oh, transcripts. Oh, transcripts. Yeah, see, I wasn't even, I don't want to say I wasn't paying attention, but I just had full confidence that you. How about that? Thanks. I really appreciate that. So before we begin, I just want to thank everyone who suggested topics to cover for this season. Like, we got so many amazing requests. So I think that we can essentially keep doing this podcast until the end of time because literally like hundreds and hundreds of suggestions.

Yes. And really good ones. Really good ones. And we also heard from listeners who really wanted to hear more in our diabetes episode about obesity and fat phobia. And in our alcohol episode, people wanted to hear more about addiction. And both of those are huge topics that we're hoping to tackle in future episodes. Yeah, absolutely.

We wanted to give them the time that they deserve. and so, like, devote entire episode or episodes to those. Yeah, exactly. And keep an ear out. Okay. With that, should we? Should we do it? I think it's, yeah, I think we should.

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order and 365-day returns, now available in Canada, too. 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 if you just hear the word typhus listeners, not Aaron, who just researched typhus for a long time, you might think one of a few different things. You might actually think of typhoid, which I know. I keep, There were a few times when I had to correct in my notes that said typhoid, and I'm like, why am I doing this? Yeah. We covered typhoid in the season opener of our last season, and this isn't that. So typhoid and typhus are two different groups of fevers.

But then even if you are thinking about typhus, there's at least three different diseases that are called typhus. There's murine, scrub, and epidemic varieties. and they all have additional names, just to really keep things interesting. In this episode today, we are not going to cover all of these forms of typhus, but although we're only focusing on one of these typhus fevers, the truth is that by the end of this episode, you will actually know kind of a lot about all of the different kinds of typhus fevers, just because while these three diseases differ,

both in terms of their causative agents and their transmission routes, And their ecology and epidemiology, they're quite different. But in terms of the actual disease or illness that they cause, they're not all that different. That's really interesting, like convergent disease characteristics. Well, the truth is they're just caused by really similar pathogens. So let's get into it briefly. I'll quickly mention the other two, and then we'll get into the meat of the episode, which is epidemic typhus. So first there's scrub typhus, which is also called bush typhus. Both of those are not great names, but they're caused by a bacterium known as Orancia Tsutsu Gamushi, and I might have pronounced that horribly. But this form of typhus is transmitted by the bites of infected mites, larval mites, which you may know of as chiggers.

Uh-huh. Very familiar. Very, very, very, I'm too familiar with them. Yeah, intimately familiar from thanks to, yeah, Kentucky and Panama and sitting in the grass when I should not have. Never sit in the grass. So that's scrub typhus. There's also murine typhus, which is also called fleaborne typhus or very confusingly endemic typhus. Very confusingly indeed. Mm-hmm, mm-hmm.

So this is a disease caused by rickettsia typhus. which is also confusing because typhi and anyways. It's caused by abacterium called rickettsia typhi. And this form of typhus is transmitted by the feces of fleas, aka flea dirt, as we learned in our Bartonella episode. And then there is epidemic typhus. And epidemic typhus is what we're going to focus on today. Epidemic typhus is also, aka lausborne typhus, and this form is caused by the bacterium rickettsia praozykia.

So this typhus, rickettsia proezechii, is transmitted by the poop, the feces. Also, is it also called dirt? I'm not sure. Of lice. And we're going to get into more detail, like deep detail about that transmission cycle in just a second. But just to kind of wrap up these other typhi fevers. So scrub typhus and murine typhus are similar diseases. And in truth, the pathogens are very similar. So murine typhus is also caused by a rickettsia.

And often you see murine or endemic typhus and epidemic typhus grouped together into what are called typhus group rickettsiosies. So these are very similar diseases, endemic or murine typhus. tends to be a less severe disease for the most part. And is Orrentia, is that a group that's closely related to Rickettsia? That's what I was just going to say. Yeah. So scrub typhus caused by an Orentia bacterium is in the same family of Rickettsia. So it's a different genus, but very similar in truth.

Like intracellular super reduced genome. Okay. Exactly. Yeah. I think it's a little bit larger of a genome than a Rickettsia, but it's still, it's a an intracellular. And the disease looks very similar, can also be very severe, but historically, as you'll get into Aaron, epidemic typhus has caused the most severe and widespread disease worldwide. Way more than I had even thought before starting. Yeah, exactly. Yeah. So that's what we're going to

focus on today. Rickettsia prauezekiah. Like I said, transmitted by the feces of the human body louse, pediculus, humanist, corporis, one of our old friends from Bartonella, right? And I'm going to go into more detail about the human body louse, and I know you are too, Aaron. I'm excited. Me too. It's so interesting as a vector for a few reasons, and I don't think we really got into this in Bartonella because we were covering so much ground.

But I know that we did talk in our Bartonella episode about just how. how host-specific this insect is. Lice are so specific to their individual host species that the human body louse is a separate louse than the human head louse. Like asterisk. Oh, well, separate subspecies. Astrosk. Oh, okay. Oh my gosh, you're killing me here. I know. I'm sorry. All right. Well, anyways, historically, they have been, which is intense. Yeah. And part of of this intensity lies in the fact that lice are really very fragile creatures. So they can live up to four to 12 weeks and body lice generally live in and on our clothing for the entirety of their life cycle. But they're incredibly sensitive to temperature and humidity. So if their host, i.e. us

humans, for example, comes down with a fever, lice will flee their hosts. So I have a quote about lice fleeing their hosts. When Thomas Beckett died in the 12th century and his body was laid out for the public funeral, onlookers noted that as his body cooled, the lice living in his clothes began to crawl out and quote, boiled over like water in a simmering cauldron, and the onlookers burst into alternate weeping and laughter. Oh, no, no, no, no, no. That's a lot of lice, Aaron. It's a lot of lice. Okay.

Well, with that lovely image in mind, lice are also very susceptible to dehydration. So in addition to human body temperature, humidity is really important. So their poop, which, again, is what contains the infectious bacteria, is really, really dry and powdery, which is an image that I never had thought of. But their poop is only like 2% water. Wow. Uh-huh. They're very efficient little creatures. I looked it up for reference, and our body poop is like 75% water.

Okay. Come on, we got to do better than that. Pretty good. Yeah. Anyways, that's a long divergence, but all of that is to say that lice, living in and on our clothes, they have to blood feed all the dang time,

like five times a day, every day, for weeks on end. And while they're doing that, in our bloodstream, they pick up these rickettsia. Now, then what happens is that these bacteria can infect the louse gut lining, the cells that line the lice's gut, their epithelial cells directly. They replicate in the gut cells of the lice, and then they burst out of those cells, which is how the bacteria

gets into the feces and then is transmitted to us when we scratch that dry, flaky poop into all of our bite wounds or rub it into our eyes or nose, etc. However, this whole bursting out of the epithelial cells thing also goes the other way. way in the louse causing blood, like our human blood that they just sucked up, to enter the body cavity of the lice because the rickettsia just burst open their fragile tiny gut. The lice that are infected then become visibly red because they're full of blood that's no longer in their guts. It's just in their body cavity. And they die within a week of infection. I had no idea that this disease kills the vectors that it uses to maintain its life cycle. It's really,

It's really interesting, and I have included a very touching quote about the poor Laos and its unfortunate journey when it encounters typhus bacterium. That's exactly how I felt. I was like this poor Laos. Yeah. Yeah. I think you'll really like it. I'm saving it for later, but I can't wait for it.

But also spoilers. Keep that whole, like, infecting the lining of something and then bursting out that thing in mind that's a spoiler for human disease too. And so for humans, in order to get infected, it really just has to be like, you said you can either rub it in a cut or stick it up your nose or in your eyes. So it really is like pretty infectious in that way. Yes, it is. And this is a disease that thrives when humans are in very close contact, sharing their clothing

or having close bodily contact in short enough timeframes that either these lice or their poop can then be transmitted person to person and complete the life cycle. Right. Okay. But yes. So it also, even if the lice dies, all of that, like, fluid from that dead louse is infectious as well. So scratching, like, the lice bodies themselves into your body can cause infection. And do we know anything about the infectious dose? You know, I don't. I didn't see that anywhere. There's a few things that I just simply did not find.

you'll get to them. That was one of them. But once we humans are infected, the incubation period, so the time from that infection to when we show symptoms is usually 10 to 14 days, which is actually kind of a long time. And then after that, symptoms generally start with like one to three days of just feeling cruddy, like non-specific malaise, just feeling bad, before the more kind of typical. symptoms, which start with a fever. A fever. Of course. This podcast will kill you. Season opener. A.k.a. It started with a fever. And this fever usually persist throughout the course

of illness until a person either dies or recovers. So it's not like a fluctuating fever. It's just you have a fever and it's going to stay like that. And is it a high fever or is it a mild fever, like it really depends? It really depends. Yeah, it kind of varies. And so does that suggest that the Rickettsia replicate better at fever temperatures, or is it a defense, or do we know? Very good question. That I don't know. That I don't know the answer to. What a good question. Thank you. But in addition to fever, there's also usually a pretty sudden onset of a very severe headache, and it's also common to have like abdominal pain. But otherwise, other than those things, symptoms are very non-specific.

Everything from myalgas, which are muscle aches, which are joint pain, maybe you'll have some chills because you have this fever, maybe anorexia or lack of hunger not eating anything because you're just feeling really bad. If it's left untreated, about 80% of people will go on to have central nervous system involvement, which can be very severe. It can be delirium or seizures or coma, which can lead to death. And very commonly, rashes are apparent. But the thing about these rashes is it's not like a single rash. You know, like with Lyme disease, it's like, oh, the classic bullseye. It's nothing like that. In some people, they'll have these like red splotchy patches interspersed with areas that if you press on them, they'll blanch, which means they'll like, you know, go to white.

Yeah. But then it also can either progress to or just start out as these like smaller red spots that don't blanch when you press on them. Or you can have patiquiae, which are like pinpoint red to purple little spots all over, like teeny tiny little dots. all the way up to like larger purplish splotches. Huh. Okay. And is that like a stage of the disease type of thing? Not just, okay.

Not from what I can tell. And what's interesting is that if you look at older studies, older studies of typhus will say like 100% of people or like a very high percentage of people all have some kind of rash at some point. But some reports, more recent reports, say only 20 to 40% of people have a risk. rash. Unsurprisingly, it's likely because, especially more recent studies that have come out of Africa, rashes in darker skin, and we've talked about this a lot on this podcast, are either not present or not apparent or not appropriately identified. And so a lot of these studies,

especially out of Africa, have been ones that have reported a lot lower incidence of these rashes associated with epidemic typhus. And like even the things like whether some something blanches turns back to white. Like that's the definitions that we use, and that's not going to happen in the same way on darker skin as it does on lighter skin. Mm-hmm. So that's the rash, which isn't specific to begin with. But that's generally the course of epidemic typhus.

Now, overall, pre-antibiotics, like before we had any kind of treatment, mortality rates were estimated to be as high as, like, 60%. which is very, very high. That's ridiculously high. Now, with antibiotics, they are estimated to be as low as 4%, which is still very high. It's still very high. And the reason that epidemic typhus leads to death or the way that it tends to lead to death can be in a few different ways.

One, it can be because of shock, and we'll talk about that a little more in just a second. The other thing is from these neurologic manifestations, which can lead to coma and lead to death. And overall, the biggest risk factors that lead to, like, who is more likely to die versus survive an epidemic typhus infection are two biggest things. Older age and malnutrition. So poor nutritional status is very strongly associated with severe infection and death compared to good nutritional status. Now, before I get into the pathophysiology, because I know you have a lot of questions, I can see them on your face. I do want to say another interesting thing about epidemic typhus, and that is that it actually leads to a chronic infection that can then be reactivated many years, like up to 40 years based on one source I read, 40 years after initial infection. And this is not from re-exposure, but just from reactivation of a latent infection.

It sounds a lot like chickenpox and how chickenpox remained in small populations. Now, I was trying to get a handle on like what percentage of people does this happen to? I do not know. I'll just say that. From what I can gather, though, it seems like if this disease is untrue, treated, nearly everyone that survives the initial infection could potentially maintain a latent infection. But if you are treated with antibiotics or through vaccination or something, there is a very

low chance of that Rickettsia surviving. Exactly. Yeah. So if you're treated, then it should clear the infection. But if you're untreated and survive, it seems like that's the population that goes on to develop this latent infection. And then the risk factors for reactivation are kind of the same things that we see for reactivation of a lot of different diseases. So like times of stress or immune compromise, like another illness or cancer or some other form of immunosuppression or even just advancing age.

So this whole chronic reactivation disease, this is called Brillzinsert disease. It gets a whole new name, of course. I'll explain why. Oh, great. I mean, it makes sense, honestly. Yeah, yeah. But it generally looks very similar in terms of symptoms to initial infection, but tends to be a lot more mild, which makes sense because your body has seen it before. Right, right.

But we clearly have questions, obviously. So let's get to my favorite part of the biology, which is like, how the heck does this happen in our bodies? Why are these the things that we see, aka the pathophysiology? Yeah, I want to hear this. Me too. Well, I want to tell it to you. So rickettsias. I know, Erin, you know a lot about these already, but listeners may also remember from our Rocky Mountain Spotted Fever episode, rickettsias are these obligate intracellular bacteria, which means they have to enter our host cells in order to be able to replicate within our cells.

Very much like a virus in that way. Very much like a virus. So when we get infected from Laos, did we decide it's called Laos Dirt? Laos dust? I like it. Okay. When we get infected from Laos dust, either from rubbing it into our skin or our eyes, the bacteria enter our bloodstream as well as our lymphatic system. And they travel to infect our endothelial cells. All of the Rickettsias do this. And every listener of this podcast probably knows what endothelial cells are by now because I feel like we talk about them all the time. But if this is, is your first episode. It is. If this is your first one, endothelial cells are the cells that line our blood vessels. So they're like the inside lining of your arteries and veins and capillaries. Rickettsia prauezekiaecii tends to infect the endothelial cells specifically in our small capillaries. Why? You may ask? Why is on my face. I don't actually know. But I have suspicions.

Okay. These are not very mobile bacteria. They can't really move on their own. They just kind of go with the flow. And capillaries are where flow is the slowest and the area between endothelial cells is really, really small. Like our red blood cells have to really squeeze to get through our capillaries. So I suspect that that is where they are most able to use their little adhesin proteins to just grab on. to those endothelial cells and then get in.

Okay. What's interesting, though, is that a lot of other Rickettsia species tend to infect larger and, like, more medium-sized vessels, and I don't know why that is. But in any case, Rickettsia Paroesechiai likes our tiny capillaries. It's found a nice little niche there. They enter ourselves, and inside ourselves, they multiply and multiply and multiply and multiply. But they're not really mobile. So they're not doing anything inside of our cells.

They're not even moving around within our cell. They're just replicating so much that eventually they fill up our cells and literally burst them open, releasing tons of new rickettsias to go on and infect the neighboring endothelio cell. Just like in the Laos, Aaron. I mean, that makes complete sense. Mm-hmm. Mm-hmm. So clearly this causes destruction of the linings of our capillaries and potentially other vessels.

It's not exclusively capillaries. Okay. This is going to cause leaking. So vascular permeability. And this, dear friends, is one of the hallmarks, not just of this rickettsia, but rickettsia's in general. So it's widespread systemic inflammation and leakage of our vessels. This is called vasculitis. So this can happen on a small scale and lead to micro hemorrhages, little tiny leaks from our tiny little capillaries.

Or it can happen on a larger scale and lead to macro hemorrhages. And so is this why we see the rashes that we see? I think that's a large part of the rashes. Yes. Absolutely. And why they can be so variable as well. Okay. Mm-hmm.

And this leaky blood and this tissue damage also stimulates a lot. lot of inflammation. So then you have white blood cells and other inflammatory markers coming to the region. And all of this inflammation can actually stimulate thromboses. So our body trying to clot off our blood so that we don't hemorrhage. See our hemophilia episode for more on that process. For about the clotting cascade. But in this case, what that leads to is then these little areas of thrombus or clot in these tiny, tiny little vessels surrounded by inflammation that then leads to cutting off of blood supply in certain areas, especially in our brain. Since this is a bacteria that by traveling through our blood vessels is able to make its way

past our blood brain barrier and infect the endothelial lining of the small vessels of our brain. Oh, oh. Right? So it cuts off blood flow to parts of our brain. Oh, that is very, that's really bad and that explains a lot. Okay. And so, this actually leads to a very specific finding called typhus nodules that are basically little blood clots in the wall or near the wall of these small blood vessels in our nervous system that are then surrounded by a whole bunch of inflammation. And that's kind of a characteristic finding of a typhus infection in the brain. Okay. And so like, You said that it, because it travels in the bloodstream, it really can go anywhere in the body.

And so is it just kind of like random? Does the inflammation ever cut off the spread of it to the brain or to other parts of the body? You know what I mean? Yeah, it's a good question. I think in general, with these kind of blood-borne infections that travel in the bloodstream, they often go first to areas of really high blood flow. So places like the brain, the liver, the spleen, and you do see a lot of involvement of those areas. But I think eventually and theoretically, this can go kind of anywhere.

So it also probably depends, too, on where the initial site of infection is and how far it has to travel and like what specific route it ends up on. Yep. Okay. Cool. Interesting. Yeah. So that's why, though, mortality is often caused by both shock. in this case because of the volume lost from these leaky vessels or from the nervous system damage that can lead to then coma and death. Wow. And 60%? 60% if untreated. Yeah. It's terrifying. Wow. I mean, that's horrific. Yeah. The good news is we do have treatment. So it's a very treatable disease. And it's actually quite easy to treat with either a one-time dose or a very short course of antibiotics. And from what I can tell, it still works really well. Not a ton of concern for resistance from what I could tell. But the other thing that's incredibly important, even if you're treating with antibiotics, is that you have to get rid of the lice. Right. So antibiotics are not enough.

You also have to be able to wash clothing in hot enough water to be able to kill the lice or leave the clothing and the bedding that are infested unused for at least a week so that they all die. So that's a huge part of both the treatment and prevention of epidemic typhus. That makes sense. Yeah. I mean. Oh, also, just like as a side note, this is a human-specific disease, except that there's some weird cases involving flying squirrels. Yeah, I'm going to talk about that a little bit. Cool. I figured. Yeah. But I thought I should just mention that like, yeah, flying squirrels are like a reservoir. I know. Of all of the animals, I was like, huh? I know. It's so random.

It's very interesting. Yeah. But that, Erin, is the biology of epidemic typhus. Well, do you want to hear about the history? I can't wait. Can you tell me everything? I will right after this break. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands

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Take five. The stay in your car, 10-minute oil change. To set the tone for the history section, I want to start with a quote about typhus from a book called Rats Lice in History by Hans Zinser, as in Brill Zinser. Oh. Quote, soldiers have rarely won wars.

They more often wipe up after the barrage of epidemic. Antifis, with its brothers and sisters, plague, cholera, typhoid, dysentery, has decided more campaigns than Caesar, Hannibal, Napoleon, and all the inspector generals of history. The epidemics get the blame for defeat. The generals get the credit for victory. It ought to be the other way around. I love that quote, and I also love that we have now covered every one of those diseases. I know.

I know. I was looking at that. I was like, wow. And I was like, we could probably throw a few more in there, too, to be honest. Yeah. Malaria. Malaria, yellow fever. I mean, trench fever, for that matter. Didn't really decide many wars, but we could definitely make a case for other words. I think we did. I think you did. I think you did. This is this idea is a common theme for our podcast, right? Like wars and unrest directly. and indirectly lead to the emergence and spread of infectious diseases, both among soldiers as well as civilians. You know, we've talked about dysentery loving a disaster. We've read some descriptions of the latrine conditions that led to typhoid outbreaks during the American Civil War. We've described how global

movements during World War I helped spread the 1918 influenza pandemic in our very first episode. And we've even talked about the human body louse in that, same war spreading trench fever, also accompanied by some very descriptive quotes of body lice and the problems with them. Very descriptive. But it's taken us this long. I still can't get over it to talk about typhus, which as you now know, with 60% mortality among untreated people, it ranks among, you know, plague, cholera, to all of those other ones in its ability to absolutely devastate a village or a city or an entire country, the historical impact of it is huge. When we think about the death toll from a war or from a famine or even from just an epidemic alone,

I think that many of us probably imagine people dying, for example, in combat on D-Day, right, or in bombings from the blitz, or maybe directly from starvation in the Holodomor, or directly from bubonic plague during the Black. death, because that's often how we learn about historical events. But even if that compartmentalization or assigning deaths to this cause and that cause, even if that's a useful way to learn, that's not really the way it happens. Alongside death in war is death in pestilence, death in famine. I mean, this is why the four horsemen of the apocalypse, which are most often represented as pestilence, famine, war, and death. It's why they ride together. Like, they don't take turns, like, showing up

and then like, okay, peace out. It's your turn now. Like, it's a partnership. True. The firsthand account that I read described a typhous outbreak in ships of Irish immigrants fleeing during the Great Famine of around 1845 to 1852. In that famine, there were an estimated one million excess deaths, and the majority were not deaths directly from starvation, but from infectious diseases, including typhus. And that same thing has happened time and time again in wars where casualties from infectious disease outweigh those from battle. And I realize, like I fully realize that right now I'm presenting a microhistory of typhus, which is like maybe a bit hypocritical about teaching things in isolation.

So I really wanted to start off this section by saying that I hope you take away from this episode an appreciation for the enormous and horrible impact that typhus has had. And also to ask you to remember that while I'm talking about typhus in Napoleon soldiers or typhus in concentration camps, typhus was not acting alone. It worked side by side, aided and abetted with other. infectious diseases as well as, you know, human-created miseries like war and concentration camps and famine. So now that that's out of the way, I can finally get to the meat of it. By first asking, not where typhus came from, but where did lice come from?

Yes. Where? We've already talked about how fascinating we think lice are, so it was really fun to get to read more about them for this episode. And I think I might have touched on some of this from our Bartonella episode, but I'm going to go over the basics as well as offer a self-correction, potential self-correction. Okay. So Rickettsia-Prawezekiae is transmitted by the body louse, as you said, which is generally considered a different species or at least subspecies than the head louse.

And it's been hypothesized that the body louse diverged from the headlouse when a human started wearing clothing around 72,000 years or so, give or take. which is, I think, what I said also in the Bartonella episode. But after doing more lice reading for this episode, I learned that the story might be a bit more complicated. It always is, isn't it? It always is. First of all, body lice and head lice can interbreed and produce fertile offspring under experimental conditions. Okay.

Which is, yeah, that's one way that scientists often decide whether things represent different species or not, but it's not like the only criterion. Secondly, there are no consistent morphological differences between the two. And species or subspecies identification usually depends on like where on the body the body the lice was found. So if it was found on the head, it's a head louse. If it's found on the body or in the clothing, it's a body louse. Under experimental conditions, researchers seem to have been able to raise body lice

from head lice. Like they take a population of head lice and they raise them under body lice conditions and you have a what looks like a body louse. Hmm. Interesting. Yeah. But there are some behavioral and physiological differences between the two, namely in that the body louse has evolved to live in clothing and lays its eggs in clothing, which head lice do not do.

And there are also size differences and sometimes color. differences between the two, although, again, those are not consistent. And until recently, it was thought that body lice and head lice were indistinguishable genetically, but more recent research has led to a molecular tool that can differentiate between them. And this finding has led to the thought that body lice and head lice aren't two different species or even subspecies, but that they represent two different egot types. and that's the result of a difference in the way that their genes are expressed, like at some point during development or growth or I don't really know about the life stages of a lice.

Fascinating. Yeah. Yeah, because I was reading that they have different feeding patterns, which they think leads to differences in vector competence, why like body lice transmit a lot of things. And it's thought that head lice generally don't, even though they can, like you said, in the lab. And also, like, the ecotype thing, there's differences in their immune responses to infection with things, which then would make body lice more capable of getting infected with bacteria than head lice. Yeah. It's really interesting. And I, like, I probably should do some more digging on this. But I wonder if it's just like a suite of genes that are turned on in one versus the other that has.

like basically over time, once humans started wearing clothing, it wasn't necessarily like a one-time divergence between the two, but like a continual divergence where a headlice populations, especially like an over-infestation are feeding into body lice populations. It's like, oh, I don't know what environmental cue it could be, maybe like an intense population pressure or something in a head lice infestation, that maybe one of them turns on those switches for the other genes. It is like, hey, I'm a body lous now. I prefer a little bit cooler. I'm going to lay my eggs out here. I'm going to feed this way. Like, it's nice to know you guys. Fascinating, Erin. Yeah. So, like, it might be semantics, whether we call them subspecies or different species or

egot types or whatever. But I just find that whole part incredibly interesting. I do too. Yeah. Yeah. Okay. So all of that nitty-gritty info aside, humans have been parasitized by lice for millions of years. And that's very typical of lice. Like they tend to be very species specific. They're often used to track like the evolution of different mammalian species. Each species tends to have their own, you know, louse species. And because of this high degree of specialization, human lice have basically followed the distribution of the species. their host, meaning that they are globally distributed and they've been that way for a long time. And even though a lot of things are working against the preservation of lice and fossils, we do have some archaeological evidence to back this up, to back this global distribution up. The oldest headlaus was found on a hair from 8,000 BCE in northeastern Brazil, and the oldest found in the old world came from roughly 7,000 BCE in Israel.

combs for head lice have been found from around 6,500 years ago in ancient Egypt, and lice have been found on mummies in Egypt, China, the Aleutian Islands, Greenland, and parts of South America. And I know this is like a lot about lice. So I want to read that amazing other quote that I alluded to earlier before I move on to Rakeshia Prabzakia. Okay. So this is also from Hans Zinser, his book. that rats, slice, in history is like a gold mine. It's a very bizarre book. I'd say that much.

It literally was, it was like 12 chapters not about typhus or rats or lice. Oh, okay. Just about history? Yeah. And like in the chapter title, he would apologize for like, I promise, this is the last divergence. It's great. It was written in 1935, I think. 32, 35. Okay, quote, The louse shares with us the misfortune of being prey to the typhus virus. If lice can dread, the nightmare of their lives is the fear of someday inhabiting an infected rat or human being. For the host may survive, but the ill-starred louse that sticks his hastellum through an infected skin and imbibes the lonesome virus with his nourishment is doomed beyond succor. In eight days he sickens, in ten days he is in extremis.

On the 11th or 12th day, his tiny body turns red with blood extravasated from his bowel, and he gives up his little ghost. Man is too prone to look upon all nature through egocentric eyes. To the louse, we are the dreaded emissaries of death. He leads a relatively harmless life, the result of centuries of adaptations. Then, out of the blue, an epidemic occurs. His host sickens, and the only world he has ever known becomes pestilential and deadly. And if, as a result of circumstances, not under his control, his stricken body is transferred to another host whom he, in turn, infects, he does so without guile, from the uncontrollable need for nourishment, with death already in his own entrails.

If only for his fellowship with us in suffering, he should command a degree of sympathetic consideration. I love it. That's so good. I have so many quotes in this. It's just, it was, I loved that so much. And gives up his tiny ghost. His tiny ghost, can't you picture it? I can't.

Oh, his little ghost, sorry. This gives up, it's so cute. It's so adorable. Yeah, that book definitely did convince me to like lice more as well. Like appreciate their incredible biology and, yeah, and feel a little bit sympathetic. I mean, it's killing them, too. Yeah. Well, anyway, let's turn to typhus.

Let's. So where did typhus come from? Great question. We don't know. What are you, me or something? So from what I can tell, it's still debated whether Rickettsia praozekiae came from the old world or the new world. For a lot of human history, the disease was grouped in with other fevers or not distinguished from typhoid. And like we said, that's a very common thing.

The origin of the words are essentially the same. Typhoid actually comes from typhus, which comes from the Greek word typhos, meaning smoky or hazy. And that's meant to describe the neurological effects that the disease can have. And I also wanted to just, because one more little thing about lice here, there are a lot of words that we use in like common English sayings that are referenced to lice. So like knitwit, lousy or like a lousy night's sleep, meaning that like you were bothered by all the lice on you. Nitpicking, going over something with a fine-toothed comb. And chatter, which I think we mentioned in the Bartonella episode. Like to pick chats, I think, or like to chat would be to like sit there and remove lice.

And so they would call it like chatter. to hang out with a group of people. And I just don't remember it. Honestly, yeah. There are a lot of episodes that I'm like, we did that. I don't remember doing that. No recollection. Yeah.

But reading back through ancient or historical writings and trying to figure out what might or might not be typhus is super tricky, as you might expect. Some people point towards some of Hippocrates' writings describing typhus or maybe the Athenian plague in the 5th century BCE, as described by Thucydides, or maybe from a battle in Spain in 1083 CE, which would put the origin as old world. But those are pretty hand-wavy. And a disease that sounds much more specific to typhus doesn't show up in Europe until the very end of the 15th century,

like as early as 1448, I think, maybe 1492. in Granada, when 17,000 soldiers died of a disease that sounds a lot like typhus. And then again, the same similar disease shows up in the 1550s in Spain. Quote, a new disease unknown until the time of the Civil Wars in Granada, appeared in Spain in the year 1557 and depopulated the greater part of our peninsula. It did not begin to decline until the year 1570. And, and, and, you know, And around the same time, or a few years before, there are descriptions of what was clearly typhus in Mexico. And the disease continued to pop up in epidemic form every time there was a drought or famine up until the 1900s. And I feel like either of those examples could be used to say, see, it's clearly old world origin, or see its clearly new world origin.

So what can the Rickettsia tell us about itself? as we probably discussed in our Rocky Mountain spotted fever episode. Riketia are these super small and bizarre bacteria. They're really closely related to mitochondria, the powerhouse of the cell. And they're very tricky to culture in a lab. And for a long time, researchers were unable to find a non-human reservoir for Riketia Praozekii. But then people began finding antibodies to the rickettsia in Scylla. some domestic animals such as like donkeys in parts of Africa, but it wasn't always consistently

found. So like that didn't seem, that seemed like an incidental infection, like that didn't really seem like that was the source. But as you mentioned, Aaron, one place where it does seem to be more consistently found, and I'm talking about like antibody prevalence rates of 40% or so, is in, yeah, this, the southern flying squirrel, which is found in like the eastern half of the U.S. and down into parts of Mexico. I mean, it's just so random. It is. And I want to know more about it. But yeah, like that, that right there says to me, okay, that's a big check in the new world origin column. But I'm still not convinced because of the timing of those outbreaks. So like, did somehow it just spread in the population? Are they affected by it? Like,

A lot of exposures in the eastern U.S. seem to be associated with these southern flying squirrels. So, like, what? It's just strange. It's very strange. I don't get it. I mean, but in a way, it also makes sense because, like, I think we talked about with the Rickettsia, Rickettsiae I, also finding a non-human reservoir is challenging to do, but small rodents do seem to be, like, very good candidates for the non-human reservoir. So I don't know. But of all the small rodent, I know.

I know. There's no like association with humans. There's no, you know, or at least not a strong one. Yeah. Like maybe there's something in the biology that somehow it just happens to work that way. Yeah. Yeah. Or maybe we're just not looking enough.

Like, you know, that's also a possibility. Definitely impossibility. So yeah, I mean, maybe we don't have a satisfactory answer right now for where exactly Riketia Praozakiai came. from. But it seems that once it showed up, it spread around the world pretty easily, especially under conditions like war and famine and unrest, which, I mean, seemed fairly consistent throughout the 1600s, 1700s, 1800s, a lot of the 1900s. And wherever it originated, it would always find the vector to be able to transmit it, right? Because body lice were already globally

distributed. Right. Analysis of dental pulp, our fave. from remains in a mass grave in France from a siege in 1710 to 1712 shows evidence of Rickettsia praozakii infection and it was also found again in dental pulp in the remains of some of Napoleon soldiers in a mass grave in Lithuania from the 1812 campaign.

It's amazing what ends up in dental pulp. They also found Bartonella, which I may have even mentioned those papers in the episode, I'm not sure. Again, I have no recollection of previous topics. But the second finding, the one of Napoleon's soldiers, it lends support to the idea that typhus, along with other diseases, may have been a major contributing factor to Napoleon's decision to retreat during the Russian campaign. And I don't see how he would have had any other choice, because listen to these numbers. Oh, dear.

Of Napoleon's 500,000 soldiers, half a million soldiers that marched to Moscow in 1812, 3,000 returned. Yeah, out of 500,000, 3,000 returned. That is incredibly depressing. Uh-huh. And an estimated 20% of the mortalities were due to typhus. 20% due to typhus alone, is the estimate? alone. I mean, typhus aided and abetted, you know, by all these other things as well. But like, yeah. Oh, my. So that, yeah, it's a lot. And not long after this, Napoleon's, you know, ill-fated

campaign to Moscow, typhus began to be distinguished as a separate disease from typhoid, although confusion seemed to linger, like it had been differentiated once before, but like people were still not sure, like, is this typhus? Is this typhoid? It's fever. Generally, it was just fever. Feaver, yeah. But it also gained some more descriptive names, such as ship fever was a common one, jail fever, camp fever, and so on, to describe the typical circumstances under which epidemics occurred. Because it's important to remember that although body lives were prevalent across the globe, it's not like typhus was constantly occurring. It wasn't like a truceus. It wasn't like a childhood illness. It wasn't like, oh, you're just going to get it, and it's endemic here, right?

It needed a spark, which was usually provided by someone who, you know, had active typhus or who had Brill's insert disease. And then it needed fuel, which was impoverished, crowded settings and malnutrition to then lead to this devastating and deadly epidemic. Right. Even before the so-called coffin ships left Ireland for North America, like in our first-hand account during the Irish famine, typhus was running rampant across the country. I'm going to read another quote. Quote, never had conditions been so fatally favorable to the rapid spread of lice as in the famine winter of 1846 through 1847. The people were filthy.

They had sold every stitch that would fetch the fraction of a penny, and they were wearing the same rags day after day, and night and day. Their bedding had been sold, and they slept covered with rags and old coats. To heat water or wash themselves or their clothes was out of the question. They were eating their food half or wholly raw because they had no money to buy fuel. Indeed, after months of starvation, even the strength to fetch water had disappeared. Once infection had been brought into a district, it spread with lightning rapidity among the crowds brought together for relief. A brush in passing was enough to transfer the fever transmitting louse or its dust-like excrement to a new victim,

and one fever-stricken person could pass on infection to a hundred others in the course of a day. A hundred? I mean, it's easy to imagine, right? Yeah. And so that quote is from Cecil Woodham Smith, who is the author of the book The Great Hunger. And in this book, they estimate that about ten times as many people died of disease than of starvation. during the Irish famine. Wow.

Yeah. But those deaths, of course, probably would not have occurred, or at least in those numbers, without the lack of food, or rather the lack of access to food. Because this is a complicated history, but food was still being produced and exported from Ireland during the famine. Anyway. That's a whole other episode.

That's a whole other episode, yeah. And as you heard in our firsthand, those who fled or were sent away by their landlords, for North America, they often met a similar fate. I highly recommend reading more about this, about Gross Isle, Canada, and the typhus epidemic that occurred there in 1847. There's also a great short story called Ship Fever by Andrea Barrett in a book of short stories about science. It's like I really enjoyed it. I read it a couple years ago. And there's one like the titular story or whatever takes place on Gross Isle and it's so good. And we'll link to it.

on our website. Okay, but anyway, if you pick virtually any conflict or ecological disaster during the 1700s and 1800s, you can be sure that typhus was there. It was present during the American Civil War, although according to one paper I read, it wasn't as prevalent as you might expect. It was in Mexico associated with drought or crop failure. It was during the 30 years war. I mean, like you could list tons of different instances. And it's not difficult to see why typhus flourished so well in war and in famine and especially in northern climates or cooler seasons. Like let's say you're one of Napoleon soldiers or let's say you're an impoverished immigrant fleeing the famine in Ireland. If the way you kill lice, like you said treatment alone is not enough.

You have to kill the lice. And so if the way you kill lice is washing your clothes frequently, how do you do that when you're on a ship? You don't. How do you prevent yourself from becoming reinvested? You don't. I mean, do you even have, are you even lucky enough to have one change of clothes? And if you're a soldier constantly on the move, like, let's say you have a few changes of clothes, like, how are your clothes going to dry? Do you have soap?

Aren't they just going to freeze in the Russian winter and then never actually dry? Well, and even just drying them alone, it isn't enough. Right. You have to wash them in hot enough water or dry them. in hot enough conditions or leave them, like I said, completely unworn for at least five days, which that's... It's impractical. Yeah.

And I think that also kind of like serves as a good reminder of how ubiquitous body lice were. It was just normal to have body lice. Right. And if you look at a disease like typhus, which has all but ceased to cause epidemics today, which, Erin, I know you'll talk more about the numbers. Uh-huh. But I think it's easy to subconsciously think, well, you know, people just didn't know how it was transmitted. Germ theory hadn't been developed yet.

We have so much more knowledge and medical technology to prevent diseases like typhus today. So we'll never have to worry about it. And to a certain extent, that's true, right? Like knowing more about how it's transmitted certainly helps to prevent its spread. And being able to treat it or vaccinate against it has always. also help to reduce the mortality associated with typhus. But how does that knowledge help or that technology help when you lack access to medical care, or even the ability to regularly wash your clothes or have multiple changes of clothes? Typhus outbreaks, like many other infectious diseases,

are not just a matter of bad luck or being in the wrong place at the wrong time or not knowing how to protect yourself from the disease. They arise and spread in circumstances often way beyond, your control. And that's what I just kept getting from this reading about typhus, just the sense of total helplessness and horror in these typhus outbreaks. The fever appears, and there's simply nothing you can do but wait for it to get to you. Even if you know that it's an infectious disease, and that it's transmitted by body lice. Sometimes it's just that knowledge doesn't help you. Right. So when did we learn those things? Well, in 1909, Charles Nicole published his observation that the disease was transmitted through body lice, for which he was awarded the Nobel Prize in 1928. Although it wasn't until 1938, I think, that people realized it wasn't the bite of the louse, but rather the feces of the louse that transmits the pathogen. And the causative agent of typhus, rickettsiaeiae, was discovered really by several.

people, but it was named in 1916 by Enrique de Rocha Lima, a Brazilian doctor whose colleague Stanislaus von Prawasek died of typhus while investigating it, just like Howard Ricketts, who also died of typhus, if you remember back to our Rocky Mountain Spotted Fever. Yeah. I do remember that, yeah. And Ricketts died while investigating typhus in Mexico in 1910. And so Darosha Lima named the bacterium to honor these two researchers who lost their lives while studying the thing that killed them, which is sad.

Yeah. And around the same time that DeRosha Lima named the bacterium, two researchers named Wheel and Felix developed the first serological test for the disease, and more info seemed to be rolling in. Brill disease, as it was first known, had been described by Nathan Brill in the 1910s as he worked as a doctor treating Eastern European residents in New York's Lower East Side. it was a mild disease that he described, which is why he didn't consider it to be typhus initially.

Right. And it seemed especially prevalent among older people mourning the loss of a spouse. So he actually called it bereavement disease. Oh, fascinating. Yeah, which I can imagine that being a hugely stressful and traumatic experience. Exactly what I was going to say. Reactivate, yeah. Yeah.

But later it was shown by Han Zinser to actually be this reactivated form, and so hence Brill Zinser. Fascinating. But again, even with all of this new knowledge being gained about the disease and the bacterium, it continued to cause devastating epidemics. During World War I, in many countries in Eastern Europe, such as Poland, it turned endemic to epidemic among both civilians as well as soldiers. In Serbia in 1914 after the Austrian invasion, typhus broke out and caused a massive epidemic with an estimated 500,000 cases, of which 120,000 were fatal.

Oh, my goodness. During this epidemic, more than half of the physicians in Serbia died or were incapacitated by typhus. Whoa. Mm-hmm. Overall, during World War I, it was estimated to have infected between 20. 20 and 30 million people. And once the war was over, it's not like Typhus just went away. Russia especially was in a great deal of turmoil and unrest with the Russian Revolution

beginning in 1917 even before World War I ended. So there was like just chaos. And yeah. And Typhus took advantage of that. Between the years 1917 and 1921, it's estimated that around 25 million, you know, people in Russia became infected with typhus and two and a half to three million died. Like those numbers are, they surprised me because it was just, I didn't realize, like I just didn't realize. And it was this huge epidemic in Russia, along with the enormous number of

typhus infections during World War I that inspired many people to start working on a typhus vaccine. and several countries had entire research organizations devoted to this, which shows just how terrified of the disease that people were, and, you know, rightly so. So one of the most prominent of these typhus researchers in the years after World War I was a man named Dr. Rudolf Weigel. Dr. Weigel was born in what is now the Czech Republic and lived most of his life in Lavoff, which was then part of Poland, now it's part of Ukraine. At his lab in Levovof, he made great strides with developing a vaccine for typhus that didn't entirely prevent the disease, but it did make it much less deadly if you contracted it. But he faced a problem that was common to anyone researching typhus or other rickettsial diseases. Riketia were notoriously difficult to maintain in culture and lab settings, and it was also hard to get enough material to make the vaccine, like the manufacturer.

side of it was hard. Mice and guinea pigs didn't really seem to become infected with rickettsia prozegiae, so they weren't a great solution. So faced with this challenge, Wigel came up with another solution. Use the louse as the maintenance animal. Grind up infected lice and then inject that into the butts, like through the butts of uninfected lice to infect them, to then you get more infected lice, you get to make more vaccine. Which, like, that seemed to work, actually. Through the butts. Like, that's so specific.

I know. Well, it was something about, like, the kite-ness or whatever, like, the material was, was, like, hard enough that you could, like, actually injected in there without destroying this fragile little louse. Yeah. Okay. That makes sense. I believe it.

Yeah. That's pretty cool. Yeah. But how do you get enough lice to make enough vaccine? Well. Uh-oh. Yeah. For that, you need a louse colony.

And for that, you know. hire louse feeders. No. Yes. No, this was an actual job created by Wigel, and it's very cool. I'm going to get more into it now and later. But essentially, you strapped little boxes containing lice to your legs or arms and allowed the lice inside those boxes to feed for a set amount of time. Okay. And if you happen to be one of those lucky louse feeders, you would be feeding up to 30,000 the lice at a time, apparently, which would produce enough vaccine material for 300 people in one week. Wow.

Okay. That's pretty good. I feel like it's a pretty noble job. And it was also decent paying. And I would say relatively safe. Okay. Because if you had never had typhus before, you were only allowed to feed the uninfected lice.

Okay. And if you had had typhus, then you could earn a bit more money by feeding the lice that were infected. But it did lead to some unfortunate side effects like blood loss and, you know, allergic reactions on occasion. But still, by the 1930s, Wigel's lab had become the world's typhus lab. People came from all over to study his Laos colony and to learn how to make the Wigle vaccine. Basically, he would put as many as 50 lice into what was called the Wigle clamp, where their little lice butts would put. were perfectly positioned for being injected with a slurry of their infected dead friends.

Oh, my gosh. And then those infected lice fed on more human blood, and then they were dissected. Their intestines removed, and then homogenized, then centrifuge, then diluted with saline and phenol, which would kill the bacteria. And then, boom, there's your vaccine. Wow. It's basically just, like, you know, mushed up lous intestines. Yeah, lous intestines inactivated.

Yeah, inactivated. As the years went on, the need for louse feeders grew, as the need for the vaccine grew, especially as it became clear that war was on the horizon. And even before World War II began, Jewish academics in Poland faced many challenges, often being completely prohibited from working in academia. In 1937, for instance, a law was passed that Jewish people had to remain standing in university classes in Levalph. And Weigel, for his part, rejected these policies, for example, by saying, well, I'm not going to sit down until they can sit down, which is something that many of his colleagues were either too afraid or too prejudice to do. But war was inevitable, and German forces invaded Poland on September 1st, 1939. followed by Soviet troops, and Poland was partitioned between the two. During first the Soviet occupation and then the Nazi occupation of Levovolf, Weigel was forced to keep working at his institute, producing typhus vaccine.

When so many other Polish intellectuals were being deported or imprisoned or just outright killed by both Soviet and Nazi troops, why were Weigel and his lab still there? not just allowed to work, but like forced to work. Well, it's because typhus was a terrifying threat, and so Weigel's work was viewed as invaluable. And under German occupation, Weigel's institute grew rapidly, where it served as often the only means of survival for many Polish people who faced death, starvation, or deportation. Weigel went out of his way to hire hundreds of people as Laos feeders, often Polish-neux. intellectuals or Jewish people, people who were under incredible threat from Nazi occupation. And it's not certain exactly how many Polish people ended up working at the Institute as Laos Faders,

but it's been estimated between 1,200 and 3,000. Wow. Which is a lot. I also, I feel like this is one of those rare instances in this podcast where he's using humans in his research. in a more ethical way? Yeah, no, I mean, absolutely. Like, it's a job. Well, and I didn't include this, but, like, I also read that he was really hesitant or

resistant to doing human trials of the vaccine. So, like, he had developed this vaccine in theory, but he was like, I don't want to test it on anyone. Yeah. It's dangerous to do. And so his research assistants, like, took it upon themselves. One guy injected his wife with a vaccine and then had an infect, louse feet on her. I was like, excuse me. That's, that's a bit extreme. But, um, but yeah,

so other people did the, you know, the, I don't know if we can call them clinical trials, but yeah, he, he did seem genuinely concerned. Yeah. And it is one of the rare instances. However, don't speak too soon because there will be. I, I've been waiting for it. Yeah, yeah, the other, the other shoe will drop. Yeah. Yeah. So all of these people, like, this was, their lifeline, right? Working as the louse feeders. And while feeding the lice, people often sat around and chatted exchanging ideas about philosophy or mathematics or I read one description of a conversation about why salt is used to make ice cream, but it's also used to melt roads, like melt ice on roads. So how does that work? And there are some great pictures of the louse

feeding and some of these common areas where people are just sitting around with lous. louse cages on their bodies. I'll try to post those. But the conversation during the louse feeding, it wasn't always about like, you know, philosophy or even trivial things. About half of the feeders were actively working in the resistance. And the louse feeding was a great cover, right? It allowed them to get out of the house and also to have free time for underground activities. And the institute wasn't just a place for resistance talk, but also resistance action. workers would sabotage the typhus vaccines intended for German soldiers, making them much less potent, while tens of thousands of full-strength doses were smuggled out of the lab and into the Jewish ghettos,

where lice infestation was incredibly high. Oh, my goodness. Yeah. And just to illustrate, again, because I think it's difficult to imagine how extreme, infestation could be. So this is a quote from Henrik Spillman. I know that I mess up that pronunciation. I'm sorry. Describing lice in the Warsaw ghetto in his memoir, The Pianist.

The lice, quote, crawled over the pavements up stairways and dropped from the ceilings of the public offices. Lice found their way into the folds of your newspaper, your small change. There were even lice on a crust of the bread you had just bought. and each of these verminous creatures could carry typhus. The black market vaccines from Weigel's lab did help save thousands of Jewish people from a death due to typhus. But few of these people survived the concentration camps that they were ultimately sent off to. So I don't think that I've adequately described yet just how terrified the Nazis were of typhus and how they use this fear as an excuse to enact horrific policies.

Because typhus wasn't seen as this universal threat from like, oh, this, you know, bacterium or this louse. Anyone could be impacted. It was, of course, blamed on Jewish people. Nazis used typhus as part of the justification for the construction of Jewish ghettos. And public health orders for bathing and de-lausing often had this undertone of anti-Semitism, like beards were ordered to be shaved, for instance. And just to note that there are no new evil ideas under the sun, this is not the first time that an ethnic group was blamed for the spread of typhus, and that typhus was used as an excuse for genocide and murder. For instance,

during World War I, there had been brutal medicalized torture carried out on prisoners of war or political prisoners, and also just like straight up genocide, like when nearly 50,000 Armenian refugees were placed into concentration camps and most were murdered, with typhus often used as an excuse. And upon entry into the Nazi concentration camps during World War II, people had to undergo disinfection and quarantine because the Nazi soldiers were incredibly scared of the disease spreading to them, hence the stripping and shaving and chemical baths. A single louse was sometimes used as an excuse to torture hundreds of people. But these, quote, sanitation efforts did next to nothing to stop the spread of the disease among those imprisoned in the concentration camps and prisoner of war camps. To illustrate,

by November 1941, the German army had captured one and a half million living Soviet prisoners of war and placed them in labor camps across Europe, where 15,000 died of typhus each day. Yeah, with additional deaths due to starvation and cold and likely other infectious diseases. And this massive increase in typhus prevalence put Germany in a typhus panic by 1942, and they looked beyond vaccines for help to prevent the spread. Zyclan B was developed as a disinfectant for lice, as like a de-lauscing agent, and it was found to be extremely successful in killing the lice, but it was also found to be extremely toxic to humans. Of course, this toxic side effect was included in the report of the chemical, like for like the

final analysis of like, this is, you know, where we stand at its development. And Heinrich Himmler happened to read this report. And he was like, wait a second, I know where we can use this. And so it gave him the. idea to use it in gas chambers and concentration camps, like the fact that it was deadly to humans. And so Zyklon B, gas, which was originally developed as a de-lousing agent, to prevent the spread of typhus, was used to mass murder millions of people at Auschwitz and at many other concentration camps. I know. I'm sorry. This is like super difficult and sad and frustrating history.

history to hear, but I think it's important to learn and remember. Yeah. You know, when you learn, or at least when I learned about the Holocaust, you hear about diseases in abstract. Like, yes, conditions were poor and infectious disease was rampant, but to hear about it in more concrete terms, I think it's an important context. Yeah, exactly. Well put. I struggled with like trying to articulate this in my notes and I was just like, we need to learn about this. And yeah. But there is, so there's one more sad tidbit that I want to share because I think, again, it's important to like learn this history.

And then I'm going to talk about maybe not at uplifting, but an inspiring part of the story. Despite all of these, like I said, sanitation efforts, despite all of this fear surrounding the spread of typhus in concentration camps, the disease continued to spread there, like, throughout the entire war. And I learned in researching this episode something I didn't know, which was that Anne Frank likely died in a typhus epidemic that killed 17,000 people at Bergen-Belsen in the last months of World War II. I just, I didn't, you know, like you don't, again, like you said, we learned about these diseases in abstract. Oh, typhus killed this many people.

Typhoid killed this many and dysentery killed this many. But like, it's, yeah, placing it in the context. So there are no good estimates that I could find for the total number of people who died of typhus and concentration camps or prisoner of war camps during World War II. But I'm sure that it's a staggering number. All right. So now for a last, maybe slightly less depressing bit of World War II history. There was a Polish physician and biologist named Ludwig Fleck, who worked alongside Weigel in his laboratory during the 1920s. And like Weigel, he worked on typhus vaccines and typhus biology, but unlike Weigel, Fleck was Jewish and so was eventually excluded from academia entirely, like just prohibited from working there. And so he started a private lab, and he remained connected

to the academic community as much as possible. And in many ways, he was like way ahead of his time than his peers in terms of like the use of statistics in his research and also in his philosophical approach to science. He was interested in the sociology of science in the way that people thought about scientific questions, the philosophical matter of what is sickness and what is health, like where does where is that line drawn? And he felt very strongly that advancements in science and medicine were not made by one person, but by a community working together, a concept that would inspire Thomas Kuhn when writing his structure of scientific revolutions a couple decades later. And Fleck was also concerned with the growing division between

science and the humanities, and with the fact that as scientific knowledge grew, it became more inaccessible to non-scientists. So, like, I think we can really appreciate, as a science podcast, we can really appreciate that last part in particular. But as a Jewish researcher in Nazi-occupied Poland, he was not free to express any of these thoughts, really. And this is a very condensed version of Flex Story. And if you want to read more, I will recommend a book called Dr. Weigel's Fantastic Laboratory. But anyway, during the occupation, he was commandeered by SS doctors, who first had him work at a Jewish hospital, where he began working on a typhus vaccine to try to give to the Jewish patients that he treated

and to also smuggle it out to the ghettos as well. But unfortunately, the Nazis grew suspicious that he was trying to help people. And so they sent him and his family to first Auschwitz and then Buchenwald, not as prisoners, per se. I mean, although they were prisoners in everything but name, right? Like couldn't move freely or, yeah, they always had the threat of death hanging over them. but he was sent there to conduct research on typhus, specifically a vaccine. Horrifying medicalized torture plans were drawn up initially by the SS doctors in charge, of course, and there was medicalized torture carried out during World War II, absolutely.

But thankfully, those specific plans were not something that Fleck had to carry out. Rather, he was tasked with making a vaccine for typhus to administer to Nazi soldiers. and he did what he was asked. But this vaccine was a vaccine in name only. It wasn't real. It didn't do anything. Yeah. He and some of his colleagues who were in the know were making a fake vaccine that was just absolutely nothing that they sent out to the German troops,

while at the same time making a real vaccine that they administered to the people who were imprisoned in the camps. Wow. And they kept up the charade when anyone suspected them of not sending a real vaccine. Like, people come back and be like, hey, people are still getting sick. This vaccine isn't working. And so then they had like a little vial of real vaccine on the ready to be like, no, here it is. Go ahead. Test it.

Do it you want with it. And they did this. So I just, I love like, I don't know, I really liked reading about that act of resistance. And they kept this up for like, you know, quite a bit of time. And the truth about this vaccine sabotage came out in the Nuremberg trials for the Nazi doctors. And when they learned about it, they were shocked and outraged. They were like, you haven't shown any humanity. How could you do that to us?

And like literally when they said that, people in the courtroom just laughed. They were like, you haven't shown humanity because you gave fake vaccine to people. who were literally carrying out genocide? Okay. Oh, wow. Okay. So going back to, I feel like, I feel like what has become the theme of the history section, in World War II, people knew what the causative agent of typhus was. They knew how it was transmitted.

They could test for it. They could vaccinate against it, even. But yet it's still infected and killed an untold number of people. People from whom treatment or vaccines were withheld, intentionally, people who were forced to live in conditions that were absolutely perfect for the spread of typhus. Outside of the concentration camps, typhus wasn't nearly as prevalent as it had been during the First World War. Most American troops, for example, were protected by the vaccine developed by Harold Cox at the Rocky Mountain Biological Labs in Hamilton, Montana. And shortly after

the war, Chloromethenicol and other antibiotics were found to be effective against typhus, which did help bring down, like, the mortality rate. But again, typhus lingers. Like, it still lingers. It infected and killed many people in the Gulag in the Soviet Union, for instance. And it often pops up when large groups of people are displaced due to conflict or ecological crisis. So I think I have three take-home points from this. At least three.

I mean, probably more that I'll realize, but whatever. Number one, typhus is much more devastating and has had much more of an impact than I realized before doing this episode. Like, wow, yeah. And number two, it just reinforces, again, the idea that medical technology and knowledge alone doesn't prevent disease. And three, that typhus may seem like a disease of the past, like a disease of just in the history books. But it's still here and it's unlikely to go away forever. It can and has popped up in these times of conflict of food shortages or ecological disasters, and more of those are on the horizon. Yeah.

And I don't really get the sense that we're prepared for that. So, Aaron, what's going on in the world of typhus today? How is that segue? Oh, gosh, Aaron. Let's try and figure it out together. Okay. I like that. I can do that. Right after this break.

Turns out, Erin, it is incredibly difficult to get solid numbers on epidemic typhus. Like, honestly, more so than I think any disease that we've covered so far. Whoa. The World Health Organization doesn't even have a page or a fact sheet on typhus or any of the typhus fevers. I am shocked at how tough it was. I do not have for you global estimates, period. That's period. Okay.

Okay. Like, I can't tell if that's reassuring or disturbing or both at the same time. Well, I think it's both. So let's talk about the numbers I do have. So from 1980 to 1990, so in that 10-year period, there were just over 20,000 cases reported worldwide from at least one source that I found. So at least we have those numbers, right? But like you mentioned, this is a disease that tends to happen in clusters in these outbreaks under certain circumstances. So in 1997, there was an outbreak largely in Burundi that caused an estimated over 100,000 cases.

It's, wow, that's, yeah, it's an incredible number. This is 1997. We have treatment, and yet the case fatality rate in that outbreak is estimated to be 15%, which is devastating. It just goes to show again. It's like, what does that knowledge do if you can't actually apply it? Exactly. Exactly. And to try and get more recent numbers, I found a bunch of papers looking at largely this

group that I mentioned at the very top of the episode, these typhus group rickettsiosis. So there's a number of epidemiological studies or review papers that I found that were trying to get at the epidemiology of these typhus group rickettsioses. So one of them was looking at these typhus rickettsioses in China from 2005 to 2017. And that paper determined that there was a total of 29,000 cases reported in that 12-year period, but it didn't distinguish between epidemic typhus and what they called endemic, or this flea-borne or murine typhus. But it noted that just based on the epidemiologic patterns, most of these cases fit the seasonal distribution and the kind of ecological distribution of endemic typhus, not epidemic typhus.

Okay. So that doesn't give us a lot of information about what we're focusing on for this episode. but suggests that the majority of typhus rickettsiosis in China from 2005 to 2017 was not epidemic typhus. So very low numbers, if any, potentially. On the contrary, a similar data set in the U.S. that was looking at data just from one health care like insurance group from 2003 to 2016, identified just over 1,700 cases of typhus rickettsiosis. Again, this is just one health care group in the U.S., but around the same period of time. And in that case, over 50% of those were actually determined to be epidemic typhus,

and about 40% were endemic or fleaborne typhus, and the rest may be some other rickettsiosis. So that's quite different. Yeah. Mm-hmm. Another study that was looking at febrile illness in kids in Kenya, so this is just in children, and this is just sort of like a cohort study. This is from 2011 to 2012.

They found that 1.5% of kids that came in with a fever tested positive for typhus group rickettsiosis. But again, this doesn't distinguish between epidemic and murine or endemic typhus. Huh. Yeah. And that paper also only had like 360 kids, so it's low numbers to begin with. And the treatment for those two things is the same, right? It is. Yeah. The treatment for all of this, all of the Rickettsiosies is the same, as well as scrub typhus, too. So that's at least convenient. That is quite convenient. Yeah. And another paper from the early 2000s that was looking at Northern Africa. I was trying to get like global as global as I could. I did.

into a great job, but a paper that was looking in northern Africa found no cases of epidemic typhus, and all of the cases that they detected that reacted as positive for Rickettsia Prawezekiae, turned out actually to be Rickettsia typhi. So it was all the endemic or mirroring typhus in that one study. So none of that gives us very much information to work with to try and understand anything close to like an annual number or anything like that. Well, so, okay, people are clearly still infected or becoming infected occasionally. So is that evidence of Brill Zinser disease? Or is it just the fact that like the conditions aren't often met? Or like? It's so many good questions, Aaron. So in the U.S., most of the sporadic cases are associated with flying squirrels. So bizarre but true. In other. places, it's very possible that it's maybe there's a case of Burl Zinser that then becomes a couple sporadic cases of, you know, epidemic typhus actually transmitted by lice, but that because

conditions aren't perfect don't result in like a huge epidemic. But we just don't have the numbers to know, you know. And then it's also hard because in truth, our diagnostics are not great. And so really getting a handle on, is it endemic typhus or is it epidemic typhus, you can look at the clinical picture, like, is it a less severe disease or is it more severe? But that's not perfect. And a lot of times the tests that we have will cross-react with a number of different rickettsiosis. So in a lot of parts of the world, we don't have great diagnostics. We're not getting down to that nitty-gritty. And if the treatment for the two is the same, like, then does it matter? Does the diet? Yeah. I mean, it does in like the epidemiological sense, but like for a doctor treating a patient. It doesn't. Does not. Well, it does though if there are lice, right? True. So let's talk about that for a second. Yeah, I was going to say how many people have lice, body lice, head lice, etc. I don't have a number on how many people have it. But that would be a hard number to get. It would be incredibly more difficult than typists.

Yeah. But like you said, Erin, lice are absolutely globally distributed. Body lice infestations occur worldwide. And predominantly, they tend to affect areas or populations that don't have access to either change their clothes daily or to clean and dry their clothes in a way that actually kills the lice that are living there. So very frequently, outbreaks of lice infestation. will follow large-scale disasters, like you talked about a lot in the history section, Aaron. Natural disasters, war, political upheaval, refugee camps. In urban settings, body lice are also very prevalent among those experiencing homelessness.

And I think I touched on this in our Bartonella episode. But in studies in the U.S. and Europe, anywhere from 5 to 30% of unhoused people are found to be suffering from body lice. And what all of these situations have in common, of course, is things like crowding and poor sanitation, which lead to very efficient person-to-person transmission of body lace and persistence and transmission of these lice on clothing. So I think there's a lot of things that contribute to epidemic typhus especially, although I want to point out that scrub typhus, One paper that I read suggested that it's possibly the single most neglected disease, like, of all time. I mean, oh, very interesting. Well, and I definitely think we should do an episode on it at some point in the future. Yeah.

It's very interesting. It's a very interesting one just in terms of how little people study it. But I think some of the big things that contribute to epidemic typhus being relatively understudied, definitely. I would assume, though I don't have numbers on it, underfunded compared to a lot of other diseases today, despite it being such a massive problem historically, is because I think it's very easy to ignore the most vulnerable populations who are the ones that are most likely to be affected by epidemic typhus in the case of an outbreak. Right. And it is, in fact, these most vulnerable populations, forcibly displaced migrants, of which there are an increasing number. year after year. And we talked in our dysentery episode about how many hundreds of millions of people live without access to sanitation and clean water facilities.

If you don't have access to that, how are you going to keep life off of your clothing? Right, right? Yeah. And it's essentially inevitable at this point that even barring any political instability or wars that may break out, climate change is, going to result in increasing numbers of displaced people as the frequency and severity of natural disasters continues to increase. So, yes. Epidemic typhus might not be a problem right at this moment for much of the world. However, we cannot get comfortable with that thought. No, we really can't. We really truly can't. And I think that we shouldn't be comfortable at this moment anyway, considering the fact that

there are people who, if typhus were to break out, would be very susceptible, very vulnerable. Exactly. Because we know that things like malnutrition and all of these other things that go along with increasing your risk for severe disease or death, like all of those things go hand in hand. It's really like tornadoes perfect storm of the kinds of situations that lead to these epidemic typhus outbreaks. Yeah. I think that we often touch on. the devastation that climate change could have. And it is like in a more abstract sense, right? Every time that we talk about it, we're like, well, it's going to cause food instability. It's going to cause a large movement of people. It's going to cause, you know, et cetera, et cetera.

But part of me wonders whether we're in this little, in this nice little dip in the history of typhus, right? Like right now it declined rapidly and there's not really much going on. But it's really hard to see any way that it would stay at such low levels in the future. Honestly, this season five opener is going to be akin to our season one opener where people listen to it several years later and are like, oh, how did you guys, how did you predict that? Which is, it's so interesting, though, because it's one that, like, I never learned a lot about it in any of my epidemiology classes or in anything, you know, it's epidemic

typhos, oh, it's, you know, and I mean, it is treatable, so there's that, but, you know, are you going to be able to get not only antibiotic treatment, but also, like, delousing treatment available to everyone in the midst of a disaster? No, you're not. It's not realistic. It's not realistic, yeah. And I think it's interesting, too, like, I read this somewhere, and I think Aaron, you and I were talking about this, but most typhus experts around the world today have never seen an actual case of epidemic typhus. Right. Yeah.

Like maybe you've seen endemic typhus. Maybe, maybe scrub typhus. But not likely epidemic typhus. Yeah. This is a very big episode, which we always say. But hopefully we've helped someone make a case for funding. Yeah. I mean, I think that's, that's, it's not the only answer,

but I think it is a big answer to understanding not just basic research. Right. Where did Rickettsia praozykiae come from? Right. Our body lies and headlif's two different things. You know, that basic foundational knowledge, but also applied information and programs to help de-Louse and to help keep people from being, you know, so susceptible to louseborne diseases. Oh, and because I don't think that this was made clear because you talked a lot of

lot about the various vaccines. Oh, right. That have existed in the past. No vaccine exists today. I was going to ask, but I kind of assumed, I feel like that's been the case for a few historic vaccines. A lot. Yeah. Yeah. And it's really because there have, like you said, been a lot of various different vaccines that have shown varying degrees of effectiveness. But none of them have been safe or effective enough to be licensed currently and because of lack of funding and lack of a perceived market, there is no vaccine currently. Lack of a perceived market is. Yeah.

Well, on that note. Yep. In typical TPWKY fashion, we really started off with a depressing episode. But they, they, but it's important. Again, it's just... I think it's a really interesting one in so many different ways. It is. So at least there's that.

Well, okay, on that note, shall we do sources? We should. Yeah, we shall. Okay. I had a few books in a bunch of papers. The first book is The Fantastic Laboratory of Dr. Weigel by Arthur Allen. And that's all about, like I said, Dr. Weigel and Dr. Fleck. and it's a really interesting read, a very thorough look at a very small part of history, which is fascinating. And then also that collection of short stories called Ship Fever by Andrea Barrett,

The Great Hunger, Ireland 1845 to 1849 by Cecil Woodham Smith. And the first-hand account came from The Ocean Plague by Robert White. And then, of course, I have to mention one of the most classic books, in disease history, the history of disease, even though it kind of doesn't really, it's not a great history of disease book, but it's a interesting book. Anyway, it's called Rats Lice in History by Hans Zenser. And I have a ton of papers. I'm going to put them all on the website, so, you know, please take your pick of them. Yeah, I also had a very large number of papers for this episode. I have a fair number on both scrub and murine typhus. So if this episode left you

hungering for more on those, there's a bunch of papers on both the biology and epidemiology of those. I think one of my favorite papers just on the general biology of typhus was just called epidemic typhus, and that was published in the Lancet Infectious Diseases in 2008. But there were a whole bunch more, including all of the epidemiological studies that I mentioned at the end. So you can find, all of our sources from this episode and every one of our 85 other episodes on our website, this podcast will kill you.com. Thank you to Bloodmobile for providing the music for this episode and all of our episodes. Thank you to the Exactly Right Network, of whom we're so proud to be a part.

Have you listened to all of the other Exactly Right podcast yet? You should. You should. And thank you to you, listeners, for tuning. in to our season opener. We hope you liked it. And it's going to be a good season. I think it is. I know it is. I feel it is. And an extra thank you to our patrons. We love you so much. We truly, truly do. Okay. Well, until next time, wash your hands. You filthy animals. Truck month is going on now at your local ram dealer. Hurry in for great deals and exceptional offers on a powerful selection of ram trucks. And right now, per semen. And right now, and get 0% financing for 60 months on 2026 RAM-500 Big Horn and Laramie models. Don't miss this great offer. See your local RAM dealer.

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