This Podcast Will Kill You - Ep 130 Cocoliztli: We do love a salty dish

Episode Date: November 28, 2023

In the 16th century, a series of deadly epidemics swept through much of the region of Mesoamerica known as the Aztec Empire, killing untold millions. By the start of the first of these epidemics, the area had become woefully accustomed to devasting epidemic disease, as the Spanish conquistadors had introduced smallpox, measles, typhus, and influenza, among other infections. But this disease, with its tendency to induce massive hemorrhage, fever, jaundice, and rapid death, seemed different from those now familiar infections, and so was given a new name: cocoliztli. People watched in horror as cocoliztli overtook town after town, village after village, sometimes killing as much as 80% of the population and leaving nothing but desolation in its wake. Hundreds of years after the epidemics ended, debate about the pathogen responsible for cocoliztli remains. In this episode, we’re going deep down the rabbit hole of this medical mystery, linking the spread and nature of these epidemics with the characteristics of the many pathogens that have been proposed over the years. We draw from contemporary accounts, ecological analyses, and even a recent ancient DNA study to make our evaluations, but do we ever get to the bottom of cocoliztli? Tune in to find out. See omnystudio.com/listener for privacy information.

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by her. What are you talking about? Listen to the Girlfriend Spotlight on the I Heart Radio app, Apple Podcasts, or wherever you get your podcasts. Welcome to Dirty Rush, the truth about sorority life, the good, the bad, and the sisterhood. With your host, me, Gia Judice, Daisy Kent, and Jennifer Fessler. The reality of Greek life has been a mystery for those outside the sorority circles until now. Is it really a supportive sisterhood that's simply misunderstood, or is there something more scandalous happening on campuses across the country? Let's get dirty. Listen to Dirty Rush on the Iheart Radio app, Apple Podcasts, or wherever you get your podcasts. On the first day of August, 1576, Coco Litzli began extremely strongly in

Tecama Chalko. It could not be resisted. For this reason, many people died. Young people, married people, old people, men and women, and children. In two or three days, they died of hemorrhage. Blood emerged from their noses, from the ears, from the eyes, from the anus. And women bled between their legs. And for us men, blood emerged from our members. Others died from diarrhea, which took them suddenly. They died quickly from this. That's awful. Oh yeah. It's, this. This is a This episode is loaded with quotes, Erin. Okay. That particular quote was from an anonymous Nahuah author of the Analesi de Tecumachalco from the epidemic of Cocoa Liesli in 1576.

Okay. Hi, I'm Aaron Welsh. And I'm Aaron Alman Updike. And this is, this podcast will kill you. And today we are doing a medical mystery. We are. It's our first one in many episodes. It's been years. Yeah, I think, definitely. Over 50 episodes. The last one was sweating sickness. Sweating sickness. Yeah. No, no. Dancing Plake? I don't know. Could be either. It's one of those. But yeah, this has been on our list for a while, which I feel like we say about every topic. But I'm really excited. that we're covering it because there is so much to get into. And wow, like once I started pulling the string on this, I just couldn't stop.

Like a sweater, just came all the way unraveled. Yep. I can't wait. I am thrilled because, so listeners, you may recall, or you may not, because, again, it's been a number of years, we're going to do this episode in a different way and the way that Erin and I have researched for this episode is very different than our usual. I know nothing about this story about Cocoa Lietzli at all. But I have been given a list of contenders of possible pathogens that may have caused this.

And then we're going to try and solve it, you know, in just like the next hour and a half. medical mystery that's been going on for hundreds of years. I mean, I hope that people aren't looking for full resolution like I always do when I watch Unsolved Mysteries and at the end I'm upset. But what do you mean? Like it's in the name of the show. But so brace yourselves. You'll know a lot more and maybe be able to come to some conclusions yourself.

But yeah, this will be an Unsolved Mystery. at the beginning, middle, and end. I can't wait. I'm really excited about it. And to get us started, I believe that it's quarantining time. It certainly is. What are we drinking this week? It's anyone's guess.

That's the name of the drink. Thanks to John for that title. Appreciate it. So creative. And in It's Anyone's Guess, it's delicious, and it's got a lot of ingredients, which is, you know, I think, sometimes can be fun. It's got some dark rum. It's got pineapple juice, orange juice, lemon juice, and passion fruit juice. Ooh, so tropical. And lots of juices. Yeah. It's delicious. We'll post the full recipe for that quarantini as well as the non-alcoholic and equally delicious

placebo-rida on our website, this podcast, we kill you.com, and our social media. We certainly will. On our website, you can find all sorts of things, such as transcripts, links to bookshop.org and goodreads lists. You can find music by Bloodmobile, merch. We've got some cool new merch coming out for you. You know, there's more stuff. Sources for our episodes, that's enough, right? It's a lot. There's a lot there. Check it out. This podcast, we kill you.com. Can we get started, please? Please. I can't wait. I'm primed to take notes while we talk. I'm so excited.

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In the year 1584, 75 years after Hernando Cortez first arrived in what is now Mexico, Antonio de Seudad Real and Frey Alonzo Ponce, both Spanish, traveled through much of Mexico and wrote what they saw of this once densely populated and vibrant land. quote, in times past that town had a large population, according to the older people, and now it just seems like ruins of houses. And for the many fruit trees there are in the surroundings, among which the Indians usually have their towns, especially being in the hotlands like it is. But with the Cocoa Lise, there was such a very large pestilence and mortality in that land that everything was destroyed, and now there are scarcely 200 inhabitants.

And while they named drop Cocoa Litsley specifically there, it was far from the only factor in the tremendous population losses and cultural devastation experienced by indigenous populations in Mexico following first contact with European colonizers in the 16th century. And if you'll just allow me to get on a soapbox for a little bit, even though the focus of today's episode is on just one of those factors, Cocoa Lietzli, which we'll spend a lot more time about, I don't want to lose sight of that fact that this cultural and population devastation was multifactorial, that we can't take this disease, Coco Lietzli, or these epidemics, out of their historical context without considering everything else that was going on at the time. The retrospective diagnosis is a tricky enough business as it is, and ignoring all of the social and political factors that played a role in the spread of disease, it's only going to further limit our ability to say anything about whether Kokoly was rodent-associated or waterborne. For way too long, many historians have overemphasized the effects that pathogens alone

had on the population declines of indigenous peoples living in the Americas following European contact. The concept of quote-unquote virgin soil epidemics, as in the idea that these pathogens that Europeans were more acquainted with and brought with them to the new world, that these pathogens were more devastating to immunologically naive populations, this concept has been overly used in the construction of these like Eurocentric Jared Diamond-esque histories where the strong conquered the weak and took what was rightfully theirs. Because nature, i.e. pathogens determined that they were the victors, right? Oh, no. Oh, no, no. Focusing on the role that germs alone played in mass mortality events in the Americas ignores the decisions that European

colonizers made to subjugate and oppress the indigenous populations. Inslavement, forced labor, overburdensome taxation, a complete upheaval of everyday life and repression of traditional cultural practices. Germs weren't acting alone here. In more ways than one. Yes, there were devastating smallpox epidemics. That cannot be ignored. That cannot be debated. And yes, there were also horrific measles outbreaks and influenza epidemics and so one and so forth. But it's not like in those like 80s action movies where the bad guys take turns fighting the one good guy. It's like multiple pathogens were all circulating at the same time. All the bad guys were fighting all at once. And this isn't to downplay the enormous mortality rates that we see during these epidemics,

upwards of 60 to 80% of the entire population in some cases. But it's just to try to present a more nuanced view of where those numbers, those mortality rates might be coming from. Death from disease, absolutely, may be increased by malnutrition or co-infection with another pathogen or weakened health from forced labor or fewer people to care for the sick, like societal collapse. The layers of protection from getting sick or dying from illness, in many cases, had been entirely stripped away.

And I think sometimes that can get lost in looking at these epidemics from like a purely biological, microbiological, epidemiological, epidemiological focus, I guess. And I think this is especially important to remember when we're trying to go through and guess which pathogen might be responsible for Cocoa Lietzli and be like, wow, there's no known pathogen that causes such high mortality rates. Like, well, of course, because it's not just one lone pathogen. But anyway, keeping all that in mind, now let's turn to Koko Lietzli. What were the Koko Lietzli epidemics? In short, they were a series of epidemics of undetermined cause that swept through much of Mexico and the rest of Mesoamerica during the 16th, 17th, 18th, and

possibly even the 19th centuries. Huh. At least 13 distinct epidemics, according to one paper I read. But today, I'm only going to be focusing on the two most devastating Cocolicelli epidemics, one that began in 1545 and the other in 1576, since the two most devastating Cocolesli epidemics, one that began in 1545, since they have the most documentation and had the most apparently impact on the population. But to better understand how these epidemics happened when they did and the impact they had, let's do a little bit of stage setting.

In 1519, the Spanish conquistador Hernando Cortez and his crew landed in Mexico, where they claimed the land for the Spanish crown and proceeded to travel inland until, they reached Tenochtitlan, the massive capital of the Aztec Empire, or specifically the Meshika people. Aztec is kind of a political term I learned that means really just the three tribes that controlled a lot of Mexico at the time. And one of these tribes, the most powerful, was the Mishika. Anyway, shortly after arriving in Tenochtitlan and being showered with, please go away,

gifts of silver and gold and textiles. The Spanish then took the Mexica emperor of the city as prisoner, Montezuma, for a year until he was killed. And skipping over a whole lot of history here, that really sort of kicked off the beginning of Spanish colonial rule in Mexico. Like, that is not even beginning to get into, that's not even surface level. There's so much more history there, but basically things changed very quickly in that Aztec empire, from political organization to wealth distribution, cultural practices to daily life. Agriculture shifted under Spanish rule as domestic animals were introduced, and the dominant crops switched from maize, squash, amaranth, beans, and peppers to wheat so that the Spanish could make European

style bread. Lakes were drained to prevent flooding or to provide more arable land for farming. Taxation or tributes grew enormously in demand, pretty much beyond anyone's means. And as a result, nutrition really suffered, especially since there were a series of droughts throughout the 16th century that we'll talk maybe a little bit more about later on. Many indigenous people were enslaved or forced to do labor or displaced from their homes and land. Even clothing changed, apparently, with an emphasis on European-style clothing along with fewer baths, since it was the Spanish belief at the time that bathing daily was bad for your health. Now, all of these changes did not take place everywhere or at the same time throughout Mesoamerica.

but life certainly changed for everyone. And I came across a paper about Coco Lietzli by Marr and Kiracof from 2000, where the authors wrote that, quote, certainly the policies of the Spanish colonial regime were harsh in many ways, but no more so than those of the Aztec imperial regime had been, end quote. I mean, wrong. And I think to claim that is to kind of undermine the draft. effects that the Spanish regime had on life for indigenous peoples. So anyway, when Cortez and his

crew landed in 1519, Mexico was home to a population of around 22 million people, and the major city, Tenos-Tat-Lan, had approximately 250,000 to 300,000 occupants, which was five times the size of London at the same time. Oh, wow. With an incredible intricately connected society. But within the century, millions upon millions of people would be dead from a combination of disease and the major upheaval of Spanish rule. And the first disease to make itself felt was smallpox, which began to spread in 1520, only a year after Cortez arrived. Eight million people died during the smallpox epidemic. Oh. out of a population of 22 million.

Yeah. That's, wow. Unfathomable, yep. And again, this was not just from smallpox alone, but also from the general collapse of their society. Measles, epidemic typhus, influenza, and other diseases all followed, described by witnesses as distinct diseases,

even though they may co-occur. And although the 1520 smallpox epidemic has probably received more attention historically because of how it affected the transition of power from Aztec to Spanish rule, the Cocolicelli epidemics that followed were no less terrifying or devastating. So finally getting to Coco Lietzli.

In 1545, Coco Lietzli struck for seemingly the first time. Over a dozen early Spanish and indigenous contemporary accounts describe a deadly disease that swept through Mexico and the rest of Mesoamerica. Bernardino de Saha-Goon, Franciscan scholar who witnessed this epidemic, wrote, quote, in the year 1545, there was a huge and universal pestilence where, in all of New Spain, most of the people who lived there died. At the time of this pestilence, I was in Mexico City, in the part of Tla T'Lélocco,

and I buried more than 10,000 bodies, and at the end of the pestilence, I became ill and almost died, end quote. Importantly, Saha Hogan also lived to see the second epidemic of Koko Litsley in 1576, which he described as being very similar to the one in 1545, and he ultimately died in a third Koko Lietzli epidemic in 1590. Okay, okay. Yeah. The symptoms of the illness were described as, quote, acute onset.

onset of fever, vertigo, and severe headache, followed by bleeding from the nose, ears, and mouth. It was accompanied by jaundice and severe abdominal pain and thoracic pain, as well as acute neurological manifestations. End quote. I'm listening so intently. I can hear you typing. I love it. I know, I'm sorry. I don't pick up in the mic, but I'm taking notes. Fever, vertigo, headache, bleeding, okay, jaundice, okay. And we can go over all of this at the end.

Oh, we will. Also. Yeah. In general, the duration of the disease was described as short, about three to four days. Okay. And was said to have mainly affected the indigenous population. However, sources vary on that point, which is maybe something that we'll get into later when going through the possible

pathogens. Children and young adults were said to be the most affected, although again, sort of sources are not entirely consistent on this point. But this is supported by evidence from burial grounds in Southern Mexico, where the Mishhtek peoples lived. And these burial grounds show that, A, young people were disproportionately buried, and B, bodies were stacked vertically, suggesting that the deaths happened too quickly for individual graves to be dug, which was the norm. So definitely, like, this is considered an epidemic graveyard. Okay, okay. And the bleeding seems like a key feature of this disease,

since it shows up in many of the contemporary illustrations of the epidemic. So one features a man in a full-body rash as blood or vomit flows from his face, and others also feature bleeding from the face. And written descriptions also mention the blood, quote, a pestilence in which blood poured from the nose, end quote, and someone who was writing about the 1545 Cocoa Lidsley epidemic like 60 years after it happened, wrote that, quote, blood flowed from the mouth, eyes, nose, and anus, end quote, of all people, poor and noble alike, and that the bodies were eaten by dogs and coyotes.

Okay. I think just like emphasizing the speed with which this killed and how many people are killed. Another Franciscan friar and eyewitness to both the 1545 and 1576 cocoa leesley epidemics use the term puhaimiento de sangre, meaning abundant bleeding or full-blooded. and said it was characterized by blood fevers. Notably, though, this same author used the Spanish word for typhus, Tabardio, for the 1576 epidemic. And remember, he saw both of them. But in general, this 1545 Cocolitsle epidemic was described by most eyewitnesses as distinct from other European-introduced diseases, including smallpox,

measles, epidemic typhus, pertussis, and malaria. So, in total, an estimated 5 to 15 million people died, said to be about 80% of the indigenous population. Is that in these two outbreaks combined, or just in the 1545 outbreak? Just 1545. Holy! Uh-huh. Yeah, there's a lot more detail on the 1576 one, so we'll get into that one in a second. Oh my. Yeah. 80% is what most estimates say. 80% of the indigenous population at the time. Yeah. Okay. I want to ask a million questions, but I feel like you're going to answer them. It's possible, but it's also possible that I won't at all.

But yeah, this 1545 epidemic lasted, it's kind of unclear. It probably very very very very. varied from region to region, but it seems like I've read one and a half years to four years as the total length of time, more often four years. And that's, okay, so like from 1545 till 1549, basically. Yeah. So over that time period, 80% of the population died presumably from this or related to it. Right. We know there's comorbid, et cetera.

comorbid and also just sort of like societal collapse like because this was such an intricately connected society when you don't have let's say people who are sick can't then harvest food and then people who get sick who can't turn that food into ingredients and then people who can't turn ingredients into meals and then people who can't you know it's just like becomes this thing where if you're sick, then who's caring for you? So I think that's where we have to kind of remember where those mortality numbers are coming from. Right. Because it's not necessarily all directly attributable to disease. Right. Exactly. And or to this one specific disease. Right. And you can't assume care, even like palliative or supportive care or something. Yeah. And then this, but despite that,

that is the number that's attributed to this outbreak, which took place over four years. It is what is the population losses during this epidemic, yes. And can I ask a question? Yeah. Was it like sporadic, like evenly distributed across those four years? Do we know? Was it like mostly at the beginning or mostly at the end? Was it like every spring, for example, or something like that?

Or is it just like it was these four years and that's the most resolution that we have? So for the 1545 one, more or less, that's the most resolution that we have. I think it probably started out very strong and it seems to have sort of swept through towns very quickly and very dramatically. But we do have more information in general for the 15-7. So let's get into that. Okay, please. But also I will say that the 1545 one did start in August. It started in August. Okay. Yeah. In August in Mexico. Okay. Okay. So there would be other appearances of Cocoa Litsley in the years following that 1545 epidemic, but it really came back with a vengeance in 1576. Quote, in the year 1576, a great mortality and pestilence that lasted for more than a year overcame the Indians. It was so big that it ruined and destroyed almost the entire land.

The place we know as New Spain was left almost empty. It was a thing of great bewilderment to see the people die. Many were dead and others almost dead, and nobody had the health or strength to help the diseased or bury the dead. In the cities in large towns, big ditches were dug, and from morning to sunset, the priest did nothing else but bury the dead bodies and throw them into the ditches without any of the solemnity usually reserved for the dead,

because the time did not allow otherwise. At night, they covered the ditches with dirt. It lasted for one and a half years, and with great excess in the number of deaths, end quote. Wow, okay. Mm-hmm. That is a quote from Frey Juan de Torkumara, who was a Franciscan historian, and he was describing the epidemic in Mexico City. The epidemic, this epidemic, began in June in central Mexico and quickly made its way across the land,

reaching as far north as parts of what is now the southern U.S. and as far south as the Peruvian Andes. but the vast majority of cases were concentrated in like a 400-mile radius in Mexico, where it spread from the dry plains of the north to the densely populated subtropical valleys of central Mexico, leaving almost no place unscathed, except for perhaps the coastal areas, according to some. The spread seemed to slow by October 1578, so it's like two years after. but then increased again in August 1579, ending finally in the middle of 1581. The effect was truly devastating. In Mexico, more than 2 million people died during this epidemic.

Half of the population, 51.36% to be precise. And we can be so precise because censuses were conducted a few years before the epidemic. and a few years after. Wow. Yeah. This epidemic in general, like I mentioned, is much better documented, so get ready for lots of quotes. Okay. The mortality rate was not consistent across all areas.

So one region southwest of Mexico City, Tepeyaka, lost 86.6% of its population of 60,000, while Chulula, east of Mexico City, lost only four. 40% of its 15,000 inhabitants. Only 40%. Right. An unbelievable number. Yeah, yeah. One eyewitness described its erratic spread, quote, it appears as if it is a living thing and that it goes in search of towns so that none remain, end quote. Huh. The bishop of Michua Khan wrote, quote, almost half of the natives of this province have been taken. When the pestilence enters a town, for 10 months or a year, it jumps from barrio to barrio and from house to house. And it was without order, even though divine disposition would have

had it well ordered. Because it struck one neighborhood and then jumped to another far away, sparing the one closer by. And in the same home, it took some and spared others, only to return four or six months later to claim the healthy. This was observed by all, end quote. He added that, quote, these poor Indios are half what they were in number, and the half that return are wasted, weary, and miserable, because everyone has either succumbed to the pestilence or escaped it.

And even today, the sorrowful ones who survived are still preoccupied with their loved ones who continue to suffer, end quote. So the Spanish, who seemed to be less affected by the disease, although asterisk, did keenly feel its impacts in other ways, namely economical. The accountant of the Royal Treasury of New Spain wrote, quote, the illness and death of the natives have been so great that they have been completely diminished, so much so that in many pueblos in this great land, fewer than half the population remains, and in others less than a third. And so our profits are less than they were. The absence of natives in these lands is so great that it seems unfathomable that they could have been brought to this point.

The profits are far less and are expenses ever greater because of the tremendous hardship. And the whole land is in misery, affliction, and need. End quote. That quote, like you're a tremendous hardship because your profits are down, that's gross. I know. This is a tremendous hardship if I need care for people. My goodness. Aaron, this is truly astounding.

Right? Yeah. I mean, I know I just keep saying it over and over again, but it's just like it's unfathomable. And it's there's so much here. And I think it's also. fascinating how, number one, how well this is documented, but two, how much more is still being uncovered, because for a long time, the main accounts that were used were from, were written by Spanish colonizers. And only more recently do we have people, the Nawa people, who also

wrote down histories, like those are being translated and then taken into account in these retellings, and so it's interesting. Very interesting. Yeah. Yeah. But coquolietzli, this epidemic, especially threatened Spanish rule and colonial order because of sheer population loss, not just economically, but also culturally, fewer people, to convert to the new religion, and to rule over.

And so, okay, at this point, we've established that this is, a pretty deadly disease. Now let's go through how this one was described. Yeah. Again, the Nahuat's word Kokolizli or Hue Kocolizli was used to mean pestilence, or great pestilence, and the Spanish also used malpestilencia, pestilencia universal, bad or universal pestilence. It was discussed as distinct from the other known epidemic diseases and was generally seen as something new, something unfamiliar. Some reports describe young people being disproportionately affected, while others say it attacked all ages. No animal deaths, domestic or wild, were mentioned. When it comes to symptoms, there's actually a medical description by Dr. Fernando Hernandez,

who is the physician-in-chief of New Spain. It's very long. So brace yourself, but I think you're going to find it very interesting and yes. I'm going to try and memorize it. Yeah. Quote, the fevers were contagious, burning, and continuous, all of them pestilential, in most part lethal. The tongue was dry and black, enormous thirst. Urine of the colors sea green, vegetal green, and black, sometimes passing from the greenish color to the pale. Pulse was frequent, fast, small, and weak, sometimes even null. The eyes and the whole body were yellow. This stage was followed by delirium and seizures.

Then hard and painful nodules appeared behind one or both ears, along with heartache, chest pain, abdominal pain, tremor, great anxiety, and dysentery. The blood that flowed when cutting a vein had a green color or was very pale, dry and without serocity. In some cases, gangrene and spascellus, aka necrosis, invaded their lips, pudendal regions and other regions of the body with putrefact members. Blood flowed from the ears, and in many cases, blood truly gushed from the nose. Of those with recurring disease, almost none was saved. Many were saved if the flux of blood through the nose was stopped in time. The rest died. Those attacked by dysentery were usually saved if they complied with the medication.

The abscesses behind the ears were not lethal. If somehow their size was reduced either by spontaneous maturation or given exit by perforation with coteries, the liquid part of the blood flowed or the pus was eliminated, and with it the cause of disease was also eliminated, as was the case of those with abundant and pale urine. At autopsy, the liver was greatly enlarged. The heart was black, first draining a yellowish liquid and then black blood. The spleen and lungs were black and semi-putrefacted. The bile was observed in its container.

The abdomen dry. The rest of the body, anywhere it was cut, was extremely pale. This epidemic attacked mainly young people and seldom the elder ones. If old people were affected, they were able to overcome the disease and save their lives. The epidemic started in June 15th. 76 and is not over in December when I am writing these lines. Very few with abdominal distension were saved. At the beginning, the blood was expelled by some without severe disease, then by very few. Vital energy was consumed quickly. End quote. A lot to unpack there. Was there a time frame in that description that I missed? There was not, but again, in general, three to four days, three to five. Wow, okay, okay, okay. Yeah.

Other symptoms that I saw mentioned or key observations by other eyewitnesses include the fact that it was pus that would drain out of those swollen lymph nodes if cut. And that bloodshot eyes were common and insatiable thirst was also mentioned. Lung hemorrhage was seen at autopsy. But again, bleeding does seem to be a. main feature, and the phrase, blood emerged from our noses and variations on that, appeared many times throughout accounts of this epidemic. Epidemics of Koko-Litzli continued possibly until as recently as the early 19th century, although the name used in these later epidemics was Matla Zawat, net-like rash,

and it's unclear if the new name meant new-duty. or was used in recognition of a new symptom or was just something else. Like, it's people don't know. But in any case, Coco Lietzli, especially the 16th century epidemics, has stumped researchers for decades. The symptoms described, along with the high mortality rate, don't seem to match any known pathogen today. But don't worry, there are still plenty of hypotheses to go around. Historically, epidemic typhus has been a popular guess, and more recently hemorrhagic fever,

possibly associated with rodents. This rodent association is because both the 1545 and 1576 epidemics occurred during brief, intense rainfall, preceded by long periods of megadrought, which is very similar to the Four Corners 1993, hauntavirus outbreak where deer mice proliferated after that same drought rainfall cycle. Others that have been proposed include plague, specifically mnemonic, anthrax, leptosporosis, malaria, diphtheria, protesis, lousborne relapsing fever, and malaria. All of these, I just mentioned, were proposed based on epidemiological characteristics or descriptions of symptoms, not physical evidence, not yet.

for those anyway. But there is one candidate pathogen for Cocoa Litsley that has gotten a lot of attention recently, and that is salmonella interica subspecies enterica, serivar paratyphi-c, longest name for an organism ever, maybe. But a few years ago, researchers detected salmonella interica paratyphi-c DNA in 10 individuals that were buried during the 1545 Cocoa Liesli epidemic in Wauaca in southern Mexico. Now, the researchers who published this paper are not claiming that this pathogen was solely responsible for the Koko Lietzli epidemics, but instead suggests that it may have acted in concert with other circulating pathogens at the time. But before we start debating, which pathogen is the best candidate, if any,

let's maybe learn a bit more about the ones proposed, keeping in mind, number one, what these diseases looked like, number two, how they're transmitted, number three, case fatality rates, number four, environmental factors, number five, old world versus new world origins, and number six, that this could have been the work of many factors acting simultaneously. And now, Erin, I turn it over to you. Oh, yeah. So let's take a quick break and then let's get into some of these candidate pathogens. I have so many thoughts already. So let's take a beat and then get real deep into it, shall we? Let's do it 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. That's. is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely

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You know what kids always say to me? Are you a boy or girl? Oh my God. That's so funny. I love it. So I'm always like, hi. I try to butcher it up for kids, you know, so they're not confused. Yeah, but you're butching it up is basically like Doris Day.

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When we did Dancing Plague, I remember feeling like, oh, at least some of these definitely don't fit and some of them kind of fit a little bit, maybe. Yeah. Yeah. This, I'm like, um, so let's get into all of these different proposed. I have feelings about it, and I'm going to have some more questions for you to be able to try and, like, parse out some of this. Yeah, great. Let's, let's dig in. So the list that you told me, Aaron, or at least the ones that I definitely researched, included hantavirus, epidemic typhus, pneumonic place. leg, leptosporosis, bartinolosis, measles, smallpox, malaria. An unknown hemorrhagic fever virus.

My personal favorite. It's just like choose your own adventure, like just attribute traits that have not been observed in one virus, but that's fine. Yeah. And of course, salmonella enterica paratyphi, C. Mm-hmm. Some of these, I think we can very quickly and very easily discard. As the main contributor, yeah. As the main contributor, because they not only just don't match symptoms-wise, but like you

importantly mentioned, these were things that circulated and were described very differently. Right. Right. So that includes something like smallpox, where one of the predominant symptoms of smallpox and something, Erin, that you really didn't mention at all in that list. of symptoms is a rash. Yeah, okay, rash. Interesting. So there was that one illustration of the 1545 epidemic that did depict someone with a full-body rash. But in general, it was not consistently mentioned. And in 1576, there was that Franciscan scholar who used the word tabardio, which I think

means like cloak rash or something like that. Like it refers to the rash from typhist, from epidemic typhus, but that long quote from the physician didn't describe it. Right. And in general, it was not like a – it didn't seem to be a main feature of the disease. Right. Yeah. So I feel like based on that, like smallpox is just all the way out. Like, it just doesn't fit.

It doesn't fit. Same thing with measles, quite honestly. And on top of that, measles, which – okay, side note, one of my favorite things about researching for this episode is that we have covered all of – these things. Do we do Bartonella? We did Bartonella, Aaron. We did the literal, because there's a few more things that I have on my list that you gave me, and literally the only ones that we haven't covered are unknown hemorrhagic fever. Okay. And parvovirus B-19, which like, it's not that either. Right, right. But we'll get there. Everything else we've talked about.

So this is really fun, and most of my sources are see our previous episodes. Nice. But okay, smallpox is out. Measles, we did measles a very, very long time ago now. Measles, while it spread through populations and absolutely caused a lot of morbidity and mortality, the mortality rate is nowhere near what we're seeing with Cocoa Leetsley. The mortality rate of measles was. far, far lower. And on top of that, the symptoms really are just nothing like these symptoms

that are being described. I do remember from our measles episode, they're being in entirely naive populations, measles having a much higher mortality rate. But A, again, like, I still think that the symptoms don't, like, where's the hemorrhage? Is there a hemorrhagic form of measles? Not that I know of. Yeah. Yeah. And, And so much of measles is a very characteristic measles rash. Right, right. I think the things that make it seem like measles are just the rapidity, which it seems to have swept through a population, except that like the duration of disease with measles

also tends to be longer. Yeah. Well, and I think it's interesting that you say the pattern of spread, because I think that keeping that in mind for transmission route. So that's what I wanted to get, I wanted to ask you a little bit more questions. Okay, okay. But let's knock a few more off this list first because I think there's some other easy ones. Okay.

So it's not smallpox, it's not measles. It's not malaria, I feel. No, cyclical fevers versus continuous high fever. Yeah, I mean, not to mention a lot of other things. A lot of other things. The mortality is not happening within a number of days. it's not like, that's just not how measles works. It doesn't seem mosquito-born.

Like, that just doesn't match the pattern of spread. Yeah. Hepatitis B was one that you mentioned to me via text message, Erin. I saw that mentioned in like last minute in a paper that I came across. Yeah, it was like yesterday evening. And I was like, great, more work. I love it. So Hepatitis B, again, we did this episode, y'all.

Hepatitis B causes chronic illness, and it absolutely accounts for even to this day hundreds of thousands of deaths every year, but it's a chronic infection. It's not something that is acutely killing people, at least not at this scale. So it's not hepatitis B. It's not parvovirus B19, it seems to me. This is one that we haven't covered, so I'll just briefly mention it. And even just doing this little dive on it for this episode, maybe you want to do. do parvovirus? It's on our list. I definitely want to do parvoviruses, yeah. Yeah. So parvovirus B-19 is one specific parvovirus. These are DNA viruses. They're transmitted person to person by respiratory

droplets. They can be quite infectious and tend to infect kids more than adults, mostly because you develop immunity to it. But the disease that we tend to see in majority is a pretty mild illness, though it can cause an aplastic anemia. And I think maybe that is where there is this potential looks like there's a connection because a lot of the symptoms that you described, not necessarily with regards to hemorrhage, but in that 1576 description of everything being pale and the blood being pale and et cetera, to me that means we're not having enough red blood cells for one reason or another. Aplastic anemia means that your body stops making red blood cells. And that's because in the case of parvovirus B-19, it's replicating and destroying

your red blood cell precursors, replicating in and destroying your red blood cell precursors. Interesting. And so it can cause this transient, usually, anemia where you basically can't make any more red blood cells, which can be really dangerous. But again, it doesn't happen in everyone. It's not killing people outright. It's not causing this massive amount of hemorrhage, et cetera, et cetera. Right. And it does, like, it does make me think based on that description and the amount of hemorrhage that was happening, that the paleness may have been due to that more than a plastic anemia.

But I like that's interesting. Yeah. And it sounds to me like there's multiple things going on in the description. So I want to get into like my thoughts on it and then talk about the more likely. candidates. Okay. What were some of the others that you told me that seem easy to say, I don't think it's that. Bartonella, do we already talk about that one? We haven't talked about Bartonella yet. Let me scroll through my nine-page table. Oh, liposporosis and pertussis and diphtheria. Oh my gosh, Erin, you did not tell me diphtheria and protossus. Okay, well, we can rule those out.

Like, there were no respiratory symptoms described. There were no respiratory symptoms described. So because of that, I actually think that pneumonic plague is not likely to be a cause of this. And it's interesting because some of what was described in that 1576 outbreak sounded a little bit like bubonic plague. Oh, with the lymph nodes? With the lymph nodes and these ulcerated nodes behind the ears. Like you have, you know, a pretty decent chain of lymph nodes back there. And pneumonic plague, which is a form of plague caused by your ears. Ceres, Season 1 for more details,

bubonic plague would cause these very inflamed lymph nodes, these boobos, though generally throughout the body and not necessarily only in one place. And it was pneumonic plague that was the most deadly. And with pneumonic plague, generally, the symptoms very much were pneumonia-like. You had symptoms predominantly in the lungs, and people tended to die from respiratory failure and not from hemorrhage. Like it sounds like happened here. Yeah. I will say that pneumonic plague is something that killed people very rapidly when it happened, often in as little as 24 hours.

And the untreated fatality rate for pneumonic plague is nearly 100%. Yeah. So is it possible that there was. plague going on that was causing bubonic, mnemonic, even septicemic plague. I mean, it certainly seems possible that that was circulating. I mean, and this is what I find interesting, though, because it was, like, plague was a known entity. That was going to be my question, is how much, and I would have to go back and listen and re-remember, how much plague was kind of already well-described and well known during the kind of Spanish conquistador takeover?

Well, okay. It's a good question, and this is me grasping at wisps of memories from season one. The black death happened in the middle of the 14th century, and it didn't just go away. Like, it remained in pockets. It would rear up every now and then. You know, there were epidemics of plague that happened on a regular basis. basis. And so I think given its sort of like formative impact on medicine, I would think that it would have been described or recognized as plague. Like it was, it was well known. It was familiar.

And the other thing, too, and maybe this is a little unfair, but like most papers seem to also kind of discard it or like you mention it as this was one of the ones considered or has been vested. Right. So, like, maybe we should be giving it a more fair shake, but I think that we have. Yeah. I don't think it fits. I don't think it fits. Yeah, I don't think it fits. Bartnolosis is an interesting one. Mm-hmm. So Bartnellosis, we did this, Aaron, in a very non-traditional episode way, because we covered all of the different kinds of Bartonella. Yes. I remember that, because we were like, what have we done? Yes.

Yeah. Yeah. I still feel that way. But what's interesting is that because there are so many different bacteria, so many different species of Bartonella, that cause a pretty wide variety of disease, including, so Bartonella bacilliformis is what causes Carion's disease. Carion's disease today is limited to the Andean valleys of South America, but there are many other species of Bartonella that cause things like trench foot,

baccillary angiomatosis, of course Bartonella Hensley, which causes cat scratch disease. And the symptoms don't quite fit, especially this hemorrhage. I really just keep coming back to the hemorrhage part of it. Yeah, it's hard to ignore. It's really hard to ignore. But the high fevers, the headaches, the jaundice that was mentioned in both of those descriptions, and the pallor, which could, in addition to being from just blood loss, be from a hemolytic anemia, which can definitely be seen with bartonellosis, especially with bartonellosis from Bartonella bacilliformis, which causes the most severe bartonella that we see today. So could it be that there was a different species of Bartonella, perhaps, or the same species but causing infection in a slightly different way during that time?

I don't know. Maybe. The things that make me feel like it's less likely to be Bartonella is really that this was a more protracted illness. So while the mortality rate can be very high, according to some studies at least, Carillon's disease has an estimated mortality rate of anywhere from 40 to 80 percent, although some studies suggest that the infection rate in a lot of these outbreaks was actually much higher, which means that the mortality rate comparatively was lower. Hmm. Okay. But it also is just a more protracted illness. This was something taking place over the course of one to four weeks, and people were dying at the end of this very protracted illness, which is not what was described in Cocoa Leedsley.

One interesting thing about Bartonella is that it's a bacterium. And I don't know, like I'm just not up to speed on how. how DNA analysis is done on like ancient specimens. So I don't know if they would have been able to look for Bartonella or if it would have come up. But definitely I know that they mentioned in the paper that the techniques that they used could detect bacteria, many bacterial species as well as DNA viruses, but not RNA viruses. And so I do wonder if it was there, they would have been able to find it in that. But, you know, that doesn't mean at all that it's not Bartonella just because they didn't find it. Like, again, these are very few samples in one specific

region that doesn't mean that that is what happened all over Mexico. But anyway, just a thought. Yeah, that's interesting. But yeah, I think based on the duration, like, I don't know. It just seems less, it just seems less likely. I think that one is one that's maybe not like, not quite as easy of a just dismiss it. Yeah. Because it's interesting. Yeah. Another one that I think based on symptoms is worth talking in a little bit more detail about,

but I still think is very less likely more based on kind of epidemiological data is leptosporosis. Okay. So leptosporosis is caused by the spirochet, leptospiria, many different species. This is a waterborne illness. In general, it comes to us from the urine of other animals. And symptom-wise, it seems like some things really do seem to fit. Fever is one of the first symptoms. There's generally a lot of GI symptoms like nausea and vomiting and diarrhea.

Rashes tend to occur only pretty late in the course of disease, so they're definitely not like an everyone-feetting. and they're not like a predominant feature, I guess. But what does tend to be, especially in severe disease, is signs of organ dysfunction like jaundice because of damage to the liver, like kidney dysfunction, which tends to be what ends up killing people. Okay. Like hemalytic anemia.

Okay. Right? So a lot of things are kind of ticking boxes. we do also see in leptosporosis when it's severe disease, signs of bleeding, signs of hemorrhage. And this is usually because of a decrease in platelets. But in general, it's mild bleeding. It's patiquiae, like little pinpoint purple spots. You can, however, see more severe bleeding, like massive gastrointestinal or pulmonary hemorrhage.

And pulmonary hemorrhage tends to be what kills people. in the case of leptosporosis. But this is not something that happens for everyone who gets leptosporosis. Yeah. The time course of leptosporosis is generally pretty long, and it's usually not until a kind of bifasic second round of disease that people get very, very sick. Okay. Where they actually end up dying from the disease.

Whereas this was like clearly seemed to be happening over the course of. of a couple of days. Yeah. Yeah. And the other thing that I think makes leptosporosis so much less likely is that you specifically mentioned that no animals seem to have died. Right. Leptosporosis is something that infects lots and lots of different animals and humans are dead-end hosts.

Mm-hmm. And so, I mean, on the one hand, could it be that this, like, I just wouldn't expect for it to be something that could spread across an entire region so easily. and so rapidly without having some kind of animal involvement. Uh-huh. Yeah, I feel like it would have to have been transmitted human to human. And since leptosporosis, humans are a dead-end host, you would have to have a, like, continuous reintroduction of the pathogen into the water supply.

Yeah. That's harder to imagine happening. Yep, I agree. I agree. All right. So now are we left with... We're left with, oh, epidemic typhus. Yeah.

That's our last one besides the other three. So epidemic typhus, you mentioned a number of times. Mm-hmm. And I think part of the reason that makes me think it's not epidemic typhus is just that epidemic typhus was known, it seems. Yeah. But in addition to that, symptom-wise, epidemic typhus, which is caused by Rickettsia prauezekiah, so a ketseal intracellular bacterium spread by lice. So not quite person to person, but person to person in that you're transmitting lice person to person. I mean, and like we in historical

epidemic typhus outbreaks, we see massive spread and massive mortality and mortality associated with malnutrition. Yes. We talked about. Yeah. I remember talking about that in a lot of detail. Yeah, pre-antibiotic mortality rates were as high as 60% in epidemic typhus, which fits with this. A sudden onset of fever and headache and abdominal pain are the kind of key symptoms along with central nervous system dysfunction, which could include seizures like you mentioned, and could include delirium and a lot of other things. But that's kind of where the overlap seems to end. there's really not a lot of description of hemorrhage at all when it comes to epidemic typhus. There's not the hemolytic anemia. There's not the jaundice.

There does often tend to be a rash. And rash is something that is often described as associated with epidemic typhus. And we talked in that typhus episode about the difficulties with those historic descriptions of rash because rash appears very differently. on different colored skin, and so it's thought that maybe rash was actually less common, or maybe more common, et cetera. But in any case, rash is definitely something that is described as associated with typhus, and the disease here tends to last for two to three weeks. So again, we're talking about something that tends to have a much longer course of illness.

Yeah. So I think less likely to be epidemic typhus. Okay, so we're almost done with this long list. And we've come to the few that I think are either the best contenders or that we, like you said, maybe have a little bit of evidence to suggest maybe. Okay. So let's go through these last couple and then we'll regroup, shall we? Mm-hmm. So one of the last is hauntavirus. Hontovirus, there are many different hontoviruses. Hontoviruses are RNA viruses. So like you mentioned, we would never know, at least not as of this point. Yeah. And they're generally spread by aerosolized rodent excrement.

So like rodent pee has to get in your face in order to get a haunted virus. Symptom-wise, because there are many different types of hauntiviruses that have been found in different parts of the globe, some of the symptoms do seem to fit fairly well. And certainly, synombre virus has a mortality rate of like 40. to 50% or even higher than that in some outbreaks that we've seen. The symptoms tend to be fevers, headaches, dizziness, bodyache. So it can present kind of more like the flu than what it sounds like the descriptions of this particular outbreak of Cocolice were. But it can also have nausea, vomiting, abdominal pain, diarrhea.

and when hanta viruses cause severe disease, there's a couple different forms or a couple different manifestations that they can take. One, which is what tends to be caused by synombre virus, is a cardiopulmonary disease, which causes death within 24 to 28 hours, like within a day, usually. And the symptoms are caused by vascular permeability, by your blood vessels just leaking everywhere and fluid and blood just leaking out of these leaky blood vessels. So while we don't necessarily tend to see like pure hemorrhage, we certainly see leaky blood vessels in hontavirus infections,

in synombray infections specifically. In other honta viruses like Hatton virus and pumilla virus, we do see more hemorrhage potentially, And we tend to see a cardiorenal syndrome more than a cardiopulmonary syndrome. Because I know Cocoa Litsley, we didn't really see pulmonary. We didn't really see lung involvement described. But we did see potentially kidney involvement described. And so we do see that in a cardiorenal form of a hanta virus.

But what we tend to see is just that your kidneys stop working and you stop making pee and then you die because of kidney failure. So I don't know. It doesn't, it doesn't fit that well. Okay, but it's something. It's something. Also, though, this is something that is spread by rodents. Right. So far, for the most part, with like one possible exception or two, we do not see human-to-human transmission of hanta viruses. Correct. Which doesn't mean that it can't happen or didn't happen in the past. Yeah.

But based on the ones that circulate that we recognize today, no. No. So that brings us to salmonella paratyphy. Or rather, salmonella enterica subspecies enterica, Saravar paratyphy, C. There are multiple paratyphes. There really are. And it's shockingly difficult to get information on symptoms of salmonella enterica, subspecies antirica seraphir peritaphys C, because all of the papers describe, say,

you can't tell the difference between salmonella typhi and salmonella paratyphi when it comes to the symptoms of disease, at least insofar as we know today. Okay. So we did typhoid relatively recently, and the classic description of symptoms of typhoid start with a fever. but there's a few things about typhoid that really stick out to me as not fitting with your description of Cocoa Liseley. Some of them include the fact that this fever, you mentioned in those descriptions that the fever was constant. But the fever of typhoid is usually described as not just constant, but getting progressively worse day after day.

and rising over the course of a couple of weeks. Right. So already we don't quite fit. Also, classic typhoid, and we talked about this in our typhoid episode, has a relative bradycardia. Right. Which means that your heart rate does not increase with that fever. And the description from the 1576 outbreak very nicely specifically said that you see really high heart rates. Mm-hmm.

And in typhoid, it's less likely for that to happen. Additionally, rash is a really common description of typhoid infection. And this rash, it tends to be salmon-colored little spots starting on the trunk and then kind of spreading outwards from there. And then it's usually not until the third week of this illness that you start to see GI symptoms like abdominal. abdominal pain or diarrhea. And that is when we can see some bleeding from the intestinal tract. We can see bloody diarrhea. And potentially this infection spreading to the bloodstream where you can get hypatospinomegaly, which is, again, where your liver and your spleen starts to swell. And that seems to have been described in that 1576 outbreak, where you have your liver and your spleen becoming

abnormally large and all of your organs just getting super messed up. But other than that, we don't really see a lot of bleeding. We don't really see a lot of neurologic manifestations. So we don't really tend to see the delirium. We don't really tend to see the seizures. That kind of thing is much less likely in typhoid. But certainly, mortality rate ranged from 10 to 30 percent, for the most part, if untreated with typhoid. but it is spread fecal oral, so easily spread person to person,

and there's, of course, the carrier state, i.e. typhoid Mary, meaning that it would be really easy for this to be something that could spread across a country because people could be carrying it and asymptomatic for a really long time. But in general, I feel like it's interesting, and we'll talk, I know a little bit more about this, that this happens to be the pathogen that has been found in people who likely died during this outbreak because it seems to me like the least good fit in terms of symptoms. So, okay, I definitely think, and the authors also acknowledge the possibility that this is just a circulating pathogen that was there that people had. I did a bit of digging.

I can't wait. A little bit of Google Scholaring. And one thing that I think is interesting and that this sort of reminded me of is that a paper from even like the 1980s or up to the 2000s that describes typhoid fever is going to, I think, look at a case of typhoid fever in a very different setting than historically. And this also applies to typhus, to haunt viruses, et cetera. Another thing that I also wonder about is like virulence plasmids. How, and I don't remember this from our typhoid episode, like whether there are different subspecies or seravars that contain different virulence plasmids and some are much more deadly or can cause

different sweets of symptoms or whatever. But yeah. Okay, let's talk to me about hemorrhagic fever viruses and then we'll sort of do like a compare and contrast. Okay, okay, okay. So the last kind of group of possible infections would be a viral hemorrhagic fever of like unknown type, I guess, just one of these other ones. And what's interesting about this is that, like, haontavirus is considered a viral hemorrhagic fever. Like, it's under this class of viral

hemorrhagic fevers. There's a great paper that I'll link to that kind of groups all of these into a few different categories. So we have philoviruses, which include, of course, Marburg and Ebola viruses. We've talked about both of those. We have flava viruses, which we've talked about many of these. This includes the dengue viruses and yellow fever virus, as well as a few other tick-borne and mosquito-borne viruses. The Bunya viruses, which include Rift Valley fever that we have not yet covered, Crimean Congo hemorrhagic fever virus, and of course the hanta viruses, which includes Sinombe virus, Hatan virus, etc., etc. As well as a virus called, it's a really great name, severe fever with thrombocytopinia syndrome virus that is a tick-borne virus found in China.

That's not all one word, is it? No, no, no. It's literally just like the name of the syndrome, virus. Okay, okay. Yeah. Okay. And then there are arena viruses, and we have not covered any arena viruses on this podcast. Are you serious, though?

Mm-hmm. I know. But these include Machupo virus, which is. the causative agent of Bolivian hemorrhagic fever. Right. Guanyarito virus, which causes Venezuelan hemorrhagic fever. Sabia virus, Lasavirus, Luho virus, choppe virus, a lot of different viruses that have been found across the globe in different specific regions that have caused hemorrhagic fevers of various types. Most of these, especially when it comes to a.

arena viruses, we really don't have a good handle on. Huh. Okay. We don't have a good handle on their reservoirs. We don't have a good handle on infection, like how things are spread. So just like in my pocket, I'm banking on an arena virus. Okay. For Cocoa Lucely?

Yes. Okay. Okay. Yeah. But that's just me. And I still have a lot of questions for you, Erin. So how about we pause here? We take a break.

And then we get into some more of the details about the epidemiology of these outbreaks so that we can try and parse this apart, shall we? Yes, let's do it. Can I just start by asking you a question? I was going to start by asking you a question. Oh, okay, okay. Okay. Who asks first? You can ask.

Okay. I feel like I should have asked this earlier. But like when you were going through the symptoms and this outbreak, so I know that the outbreaks themselves lasted for a number of years, like a year and a half, a couple years, four years. And people when they got infected were dying incredibly rapidly. People were dying in a number of days. But how quickly did this spread, say through a family or through a town? What was the like estimated incubation period here? Great question. I don't know.

Ugh. Maybe there are more accounts out there, but none of the papers that I read mentioned an incubation period or like a possible estimated incubation period. Wow, that was a whole entire column of my table, and I really thought it was going to help parsing support, Erin. I know, I know. So it's difficult, too, because I think, you know, the movement of it seemed really erratic. It didn't seem to move in like an outward spreading radius. It would be like all of a sudden it was there. But also let's consider the time and communication and limitations in terms of like, did that town get hit before this town? If there was two days difference or even a week difference, would that have been something detected or like even able to be observed, I guess?

Yeah. I know. I wish I had that answer. Okay, but let me ask you a question real quick. Okay. What causes nosebleed? What's happening in a nosebleed? There's potentially a lot of different things that can cause a nosebleed,

but there's two different places in your nose that you tend to bleed from. Because your nose, your nasal mucosa, essentially the skin is very thin, and there's a lot of vascular there. So most nosebleeds come from the anterior vessels, the vessels that are closer to where your nose opening is. Okay. Yeah. And you have this like plexus of vessels that if that mucosa gets dried out or if there's any trauma to it can just very easily start to bleed from that like plexus of vessels. This can also happen if you have, say, thrombose. cytopinia. That is, you don't have any platelets to be able to clot any bleeding that happens there. So there's a lot of different things that can potentially cause that anterior

bleeding. There's also posterior nose bleeds that happen farther back in your nose, and those tend to be more commonly from that type of bleeding disorder or, like, disease in the blood vessels, say from like atherosclerosis or something like that. Okay. And those posterior nosebleeds can be massive and like really difficult to stop. Interesting. And so a lot of these nosebleeds and I feel like I'm a little bit hung up on the nosebleed thing and maybe I shouldn't be. But like they do seem to be massive hemorrhaging out the nose. So could that be a combination of like some type of clotting issue combined with like what disease could do that or would do that?

how with the pathogenesis? I feel like we have talked about a number of diseases that can cause nosebleeds. Generally, when we see nosebleeds, it's not isolated nosebleeds if it's caused from, say, a hemorrhagic virus of some kind or something that's causing thrombocytopenia. But that would be one of the major things that I would think about. Thrombocytapenia is when we don't have enough platelets. And we've talked in a number of our episodes now about how essential our platelets are to be able to stop bleeding when it starts. So because your nose just happens to be a place, much like your gingiva, like in our vitamin C episode, way back when, we talked about how you get bleeding from the gums because you just don't have like any collagen left. And so it's not even about in that case not being able to stop bleeding.

It's just that that's a place that's really easy to bleed from. Okay. Your nose is very similar. Same thing with your eyes. And you described maybe seeing bloodshot eyes. So the mucosa of your eyes is just another place where things are very thin. And there's a lot of really small blood vessels. So if you have a tendency towards bleeding because you say don't have any platelets to stop bleeding,

then little tiny blood vessels breaking can lead to large amounts of blood. bleeding. Okay. Interesting. That makes sense. It's the same thing in your GI tract. Yeah. So it's not necessarily an indicator of any particular disease. It's just like, this is maybe already when things have gone well wrong. Yeah, I would say it's an indicator that your coagulation state is totally screwed up. Okay. Yeah. Okay. We saw it in, you can see it in DIC, which we talked about, so DIC is disseminated intravascular coagulation. We talked about it in our sepsis episode. We talked about it in our snake bite episode. We've talked about it in a few other episodes, but basically just anything that's

going to like completely screw up your body's ability to clot properly, you could potentially see nosebleeds. Now that being said, there are a lot of. of diseases that are considered like hemorrhagic diseases of some kind, we don't usually see described like actual, and we've talked about this in a few episodes, like, it doesn't usually mean that you're just bleeding out of places. Like hemorrhagic doesn't often mean the way that you think of hemorrhage with trauma, where like blood is just gushing out of orifices. Right.

This is not Richard Preston's The Hot Zone. Exactly. But it sounds like it is in the case of Coco Lutely. I mean, yeah. And it's interesting, too, because this does appear in both Spanish accounts as well as indigenous Nawa accounts of the disease. Yeah. All right. So before we get into more questions, let's just do a quick recap. So I have a list of the symptoms. Yeah. This is in not any specific order, but these were the ones. that were mentioned primarily in that account by that physician. So excessive thirst, continuous and high fever, headache, confusion, delirium, rapid pulse, nasal hemorrhage, bleeding from mouth, eyes, ears, genitals, tongue, black and dry, swollen lymph nodes in neck, jaundice, chest pain, bloody stool, stomach pain, sometimes rash, autopsy showed enlarged liver, black heart, dry stomach,

black lungs, urine green or black, then pale, and no notable respiratory symptoms. The disease seemed to have a three to five day duration, incredibly high case fatality rate with the overall mortality rate of like 50 to 80 percent. Again, not necessarily attributable to one pathogen alone. And there was actually that one Franciscan scholar Sahagun wrote that quote, many died of hunger and because no one was able to care for them. In many cases, every member of a household fell ill without a single person left to give them even a cup of water to the sick. End quote.

So it has also been described as disproportionately attacking young adults and adolescents. And it also has been said to have disproportionately affected the indigenous population. not all accounts describe this. And I do kind of want to get into this in a little more detail because I think it can help maybe resolve the question of old world versus new world pathogen. Okay. If this disproportionate impact on indigenous populations was a true phenomenon, where was that coming from? Right. Was it socioeconomic factors? So one person described that people who were, quote, rich, well-dressed and with a comfortable living were not affected by the disease, end quote. So was it just socioeconomic factors? And so it was a new world disease that everyone was in theory immunologically susceptible to, but it was just that the indigenous population who had been suffering the greatest losses due to forced labor and minds, enslavement.

ridiculous taxation, etc. Spanish witnesses did recognize this disproportionate impact and the living conditions and how it affected the rate of disease. Quote, the reason why so many Indians die of pestilence is a God secret. I do not find any better answer than that in the past, the Indians were not as badly mistreated and oppressed as they are today with heavy workloads. They are skinny and delicate. The disease finds them overworked and without resistance.

so they are finished, end quote. Okay, so if we do New World, then for the most part, socioeconomic factors and living conditions would explain the difference in susceptibility or attack rate or mortality rate. If it's an old world pathogen, it's probably a combination of those things. socioeconomic factors are still there. They're not going away. But it also might be something about if it's an old world pathogen,

it's quote-unquote more familiar to the immune systems of the Spanish colonizers. And there is a little bit of evidence in this respect because if socioeconomic status meant that you were not only protected from getting super sick if you did get infected, but that it also prevented you from getting infected, then we would still see high death rates among those who were exposed to disease, if that makes sense. Yeah. And so you have a bunch of these Spanish members of these religious orders who did a lot of the caring for the ill and a lot of the burying of the bodies, these priests and so on. And they are not described as having high death rates. Nor are the Spanish physicians that performed so many autopsies without the slightest bit of PPE.

So one author also suggested that maybe the reason for the disparity in these mortality or attack rates is that the root of transmission was somehow unique to the indigenous populations. Right. We don't know what the root of transmission was. But given that the Spanish colonizers and indigenous populations lived pretty similar day-to-day lives at that point, or at least not terribly drastically different in terms of completely separate. lives, it doesn't necessarily seem like it was that? I don't know. Yeah. Because if the disease was transmitted through direct contact, lice, fleas, blood, or other bodily fluids, respiratory droplets, mosquitoes or water, there's really no way that the Spanish would have just been completely spared if they had been as susceptible. So, okay, that was my sort of new world, old world thing.

Okay. Root of transmission, we don't know. We can. We can. can compare the spread of Cocoa Lietzli to the other epidemics that were happening in the 16th century, and it seems very similar to those that were spread person to person, like smallpox, chickenpox, and measles. We can go over some of the other possible routes of transmission, too, like waterborne or Laosborne or like a rodent reservoir. We kind of already touched on that. Geography, again, we only have a few accounts to rely on, but it seems like everywhere

was impacted with the possible exception of some of the coastal areas. There are many different reasons why that could be. Maybe a less virulent variant of the disease made it there. People were more immune or the vector or reservoir wasn't as prevalent or just something else interrupted transmission. Could be a whole lot of things going on. Yeah. But was that trend like persistent across the years, I guess? I don't know.

I don't know. Yeah. And then there's the environmental factors which this mega drought and then period of intense rainfall. And so some researchers have suggested that as like evidence for rodent associated, as like this proliferation of rodents, but could it also be contaminated water supply? Because we know that, you know, drought, excessive rainfall. fall and just in general, like disruption and chaos in everyday life is water supply is one of the first things to get all screwed up. And so I think it's an interesting question about like

the symptoms. Does whatever disease that actually cause this have to include every one of those symptoms? Which symptoms do we concentrate on first? Which accounts are reliable? Like what if the physician never actually performed an autopsy and he's just hearing word of mouth. Then you have a physician who's looking at someone and saying, these are the things you're experiencing, versus someone who's like, this is what I'm experiencing. It's an interesting, I don't know, interesting questions. But yeah, let's sort of get into a few of these things. So I feel like the New World versus Old World discussion plays a role in the hemorrhury. fever virus potential.

Yeah, because I think when I would think about a hemorrhagic fever virus as the causative agent, it doesn't seem likely that it would have been a hemorrhagic fever imported from the old world to the new world for a few reasons. One, because then I would expect, I don't know, something similar to have been reported somewhere else first, right? But I think that that argument stands for like any pathogen that was brought over, right? If it was something that was brought over, how could it be something brand new that hadn't been seen by the Spanish conquistadors beforehand? Yeah.

Right? And that is the part that I think makes it so hard to think could it have been anything that was brought over. Right. unless it was something that was brought, I don't know. Brought over and then mutated into a more virulent strain. Or something perhaps not brought from Europe, but brought from Africa during slave trade that maybe we was happening, but we don't have as great of records on it, perhaps. But that also still doesn't explain why Spanish colonizers seem to have been less affected.

Yeah. Per se. Unless it's just, again, down to socioeconomics and exposure and things like that. Yeah. But so many of these hemorrhagic fever viruses that we do know are transmitted direct contact through bodily fluids, right? Many. And that happens a lot, not always. the time, but a lot during caring for the sick and also taking care of the bodies of people who

have succumbed to disease. And we don't see records of like the Spanish priests dying at higher rates. Right. Well, and what's interesting is that that's a problem, I think, with lumping all of the hemorrhagic fever viruses together. Yes. The phyla viruses like Marburg and Ebola, yes, are spread direct person to person through contaminated bodily fluids. The flava viruses are often spread by mosquito vectors. So could this be something that was a hemorrhagic flava virus of some kind that we don't know of? Because I don't think that it was dengue or yellow fever. But it's just, it doesn't seem mosquito born. I mean, I feel like I don't have a good enough handle on the spread of this thing. Yeah. I mean, rapid. Rapid and sudden. Right. Rapid and sudden, which I would say probably

goes against the mosquito-borne because in general, you're going to need time for it to be in the mosquito and then causing more infection, et cetera. Well, and then like where did it come from? And why would it, why I would expect to be more infection at the coasts? Because if you have like a new mosquito coming in or even, And honestly, even a new infection coming in, it's going to come into the ports. So any kind of imported infection, how did it not come through the ports and cause more disease in the coasts than in inland? Yeah. Yeah, I don't know. But there's a lot of other hemorrhagic fever viruses as well.

The arena viruses and the boonia viruses like hauntavirus, many of those, well, the arena viruses can be transmitted a lot of different ways, including person to person. but some of them, maybe not so much. A lot of them are from rodent vectors. So could it be that it was a rodent vector disease that somehow mutated to be able to be transmitted person to person? Sure. Sure. I mean.

I mean, maybe it seems possible. Yeah. But I think that what that comes back to is how to prioritize when we're thinking about this hundreds of years ago outbreak or outbreaks, is which of these symptoms do we trust? Which of these symptoms were definitely caused by the pathogen that we think killed people in this case versus which of them were a secondary bacterial infection on top of something else? Yep. Although that seems less likely given the time course of this illness. I just can't get over how

rapid this was. Yeah. And to be honest, I don't know. And I think it also probably would have been worth me looking into what predominant understanding of disease there was. So like, was it the humoral theory of disease? Are certain symptoms emphasized over others given those sorts of biases, right? Like if someone has a fever, is that a primary symptom? Or is that like, okay, it's just a low-grade fever? Is the bleeding? I mean, that just seems so stark and so dramatic. But then there's stuff like rapid pulse, abdominal pain. A lot of these symptoms are very general. Or can be severe manifestations of many different types of infections. But there's all. But there's Also, I think, enough descriptions that tell us that whatever this was, it was a pathogen that was very rapidly affecting a wide variety of our organs.

Mm-hmm. And that was certainly causing a significant degree of what sounds like hemolitic anemia. Because in all of the descriptions, there was jaundice. In all of the descriptions, there was some amount of bleeding, be it bloody diarrhea or bloodied. bleeding from the mucous membranes. And was it truly trauma-level hemorrhagic? We don't know. But it's very likely that if you're having this degree of hemalytic anemia, that you're also having issues with your other blood cells, including your platelets, which means that you're going to be at risk of bleeding, even if it's just that like your nose is constantly dripping and not truly a

faucet coming out of it, right? Yeah. And I mean, the illustrations show gun. gushing, flowing. But yeah. But is that gushing like in combination with vomiting or, you know? Or is that like this is the degree with which we suffered? Exactly. Yes. Good point. And so I think that all of those symptoms, including, you know, the changes in the color of the urine, to me that says this is affecting the kidneys in addition to affecting the liver and the spleen. The pulse being high and the fevers, that just means you're sick, right? that could be from anything. But all of these and the rapidity of the infection just sound so viral to me. Okay. Before we go further, can I just do a little bit of a dive into the other end of things, the bacterial side of things? Okay, please. Okay, because I wanted to do a little bit of research about typhus and typhoid. Okay. So epidemic typhus was one of the earliest diseases to be proposed as the cause of Cocoa Lietzli.

Hans Sinser wrote about it in that book, Ratslice and History. Okay. During the Kokolietzli epidemics, typhus was a recognized disease, but most people did not use the name for typhus to describe what was happening. But there is a precedent for typhus being described with more superlative or extreme names, like those that emphasize. the severity of infection. And there exists at least one description from the late 15th, early 16th centuries of typhus causing a severe nosebleed. The Italian physician fracostorius wrote, quote, I have often seen cases where three pounds of blood burst from the nostrils, yet the patient died soon after, end quote. And so I got a little bit curious about typhus and

nosebleeds. And so I just put the words nosebleed and typhus, into Google Scholar. And what I actually got were primarily results for typhoid. And that's something I remember from doing those episodes. Typhus and typhoid weren't really distinguished as separate diseases until like the early to mid-1800s or so. Because they do have similar courses of disease and would also tend to proliferate during similar times of like chaos or unrest or war, even though they're transmitted differently, epidemic typhus via lice, typhoid, fecal, oral. Also, I kept coming across the phrase abdominal typhus.

That actually means typhoid, which is very confusing for me. I was like, but what is it? So, but I don't entirely know whether or not Tabardio, the Spanish word for typhus, was also historically used for typhoid or whether it was distinguished from, typhoid. I don't know. But in any case, so going back to my Google Scholaring, what I found

were a bunch of historical reports of nosebleed in people with this abdominal typhus, aka typhoid. A report of a typhoid outbreak associated with oysters that was published in 1939 describes nosebleed as a cardinal symptom of typhoid and says that in that particular outbreak, it was the most common symptom observed. And in young kids, delirium also seems to be a common symptom that we found in a different paper. But in this oyster paper, hemorrhage happened to be the most common complication. Huh.

Another paper from 1934 describes a case study of typhoid fever with hemorrhagic onset. Quote, on August 19th, 1933, at about 3 a.m., the patient suffered a sudden, profuse nosebleed. A physician was consulted who packed her nose. The bleeding, however, continued, and the patient was admitted to the hospital, end quote. And typhoid, as we talked about, can be transmitted by asymptomatic carriers.

I know that they're different diseases, but paratyphi-c DNA has been found in an 800-year-old skeleton of a woman in Trondheim, Norway. So that suggests an old world origin of at least paratyphiasee. So I think that, you know, like I said, there's a lot that historically may have been reported and may have been attributed falsely to some of these diseases like typhoid. And searching for typhus and nosebleeds or typhoid and nosebleeds is certainly cherry-picking Google Scholar.

But I did just find that interesting because I was curious. whether there had ever been something like that reported before. And then also I came across, when I was looking for nosebleeds, I came across the fact that black tongue is often another characteristic of typhus slash typhoid. People, I've seen it in both. What are the other? I mean, and maybe you could do this for literally any of the diseases, right? hauntavirus nosebleed.

Oh, I'm sure you would find it. Exactly. Oh, I kind of, can I try it? Sure. Yeah, it exists, Erin. Yeah. So maybe all we learned from that whole dive was that nosebleed is not as specific a symptom as we thought. And that these diseases can take on many different forms.

Definitely. I think that's definitely true. And, again, it's going to what symptoms you're, you have and what symptoms predominate are also going to vary depending on what the underlying immune state of a person or a population is. Yeah. But I still can't get over the rapidity aspect of it. Well, I mean, that could be influenced by immune state as well.

Definitely. But it just seems like everything at least that we know about typhoid and typhus today are longer courses of disease. Yeah, for sure. So is it something that changed? Was it a virulence plasmid? Was it a different Saravar? Or was it just acting, you know, sort of swooping in opportunistically when the person's immune system was suppressed from another pathogen? Right. Or just was there in the background not doing anything? Right. I mean, because what I think is interesting is in the paper where they found, the paratyphi in the dental pulp.

I did read that paper. That's the only paper about actual coccolids that I read. But one of the things that they said is that finding it in the dental pulp does suggest that the person or the people died with high levels of this bacterium in their bloodstream specifically. Uh-huh. Okay. Because my first reaction was, well, we know that salmonella, enterica, subspecies, enterica, blah, blah, blah, blah, blah.

Paratyphi and typhi both can very easily establish asymptomatic infections and live within us, predominantly in our gallbladder, for weeks, if not months, if not years. And so finding it in a person isn't that interesting, right, on its own, because this is something that circulates and can be present in. in people. But knowing that it's not likely to end up in someone's dental pulp upon death, unless it was in their bloodstream, is very interesting. In an epidemic graveyard. In an epidemic graveyard. However, it's still, I mean, I just, it, it's so interesting to me how much the symptoms and the time course don't seem to fit. Not to mention, and I think this is where I really wish that we had a little bit more data, like granular data, on like how rapidly this was spreading through homes and through families, right? Because when you get down as well to the incubation period of something like a typhoid, we're looking at a much longer incubation period than we are for many of the viral hemorrhagic fevers. And again, viral hemorrhagic fever, this is really, really broad. But thinking of more of the Bunia virus. or the arena viruses, which seem more likely candidates than the flavavaviruses and the filoviruses in this case.

Right. I think that the time course fits a little bit better, not to mention the mortality rate. I mean, again, we would likely be looking at something that is causing a disproportionately high mortality rate because of the population that it's affecting or because it was a particularly virulent strain or serovar or sub-serivar. But it still just seems to me to fit better in terms of the time course, in terms of how rapid the disease was, in terms of how it seems to have spread. But we don't know. We don't have that granular of data. You know, Aaron, I think I could be convinced of anything. Like, I feel like I don't.

I know so much more. And I'm just like, yep, I still. have no idea. Yeah. I feel like I just want for it to be a viral hemorrhagic fever, and I don't know why I can feel it being a bias for me right now. And I feel slightly similarly about typhoid, I think only because of my Google Scholaring and nosebleed. And the fact that, like, it was mentioned in many papers as being a cardinal sign of early disease. I don't understand that for typhoid. I don't either, especially because like I definitely don't remember reading it at all. No. And so it's like, again, there is so many grains of salt. This is like my salt shaker that it's shake it everywhere.

Right. And I do love a salty dish. So it's all always full. But we have to consider the sources. Yep. For these accounts, who's writing these symptoms? What emphasis are they placing on them? How accurate are these symptoms? How accurate is the translation? How accurate is everything? How much evolutionary gap there is between what pathogens existed then and what they look like today? How much is our care of these pathogens today influenced by the hospital systems by being able to give someone IV antibiotics, whatever, for these conditions that we're treating? We're going to do the best we can at putting ourselves in that time period, but we are super limited by both that time period as well as our own biases. So the like nodules behind the ears that were full of pus. Back to Google Scholar, we go. I mean, that doesn't sound like a virus at all. I'm about to talk myself out of a viral hemorrhagic fever because that symptom doesn't make sense. I wonder how many people that physician examined to say that that was the symptom that was seen in all of them.

That's a good question and no idea. So many of our episodes where we actually deep dive on an individual pathogen, we still have so much like sometimes the symptoms are this or sometimes it's that. Sometimes the incubation period is two days. Sometimes it's three weeks. And that's usually comes from a lack of clear data, right? And so in this case, I think it really just highlights how difficult it is to try and make these retrospective diagnoses when there's some. such limited data and such difficulty in interpreting that data, what it makes me feel like is it's amazing that we've been able to identify the causative agent of any outbreaks ever.

It's true. You know? It's true. Yeah. But it also, I think, does, like, because we have for a lot of things, it makes these kinds of ones that much more interesting because it's like, what is it about these outbreaks that have made them so difficult to pinpoint to a particular pathogen. Mm-hmm.

Well, you know, we don't know, turns out. But I had so much fun. I just want to read. Can you tell me where I can read more? I absolutely can. There is a whole lot here. So there are several papers by Akuna Soto at all that really go into a lot of these and do some great analyses of. of drought and putting forth different hypotheses. And then there is the Nature Ecology and Evolution

paper from 2018 titled Salmonella and Terrica genomes from victims of a major 16th century epidemic in Mexico. Really fascinating. But I want to give a special shout out to the supplemental information. It was the best supplemental information I've ever read. Do not sleep on it. I absolutely really appreciated the amount of work that that people put into that. And then finally, if you want to get a little bit more background on the history of the Aztec Empire and Mesoamerica, there's a great book called Fifth Sun by Camilla Townsend that I really enjoyed. I actually didn't have that many papers for this episode because I mostly just read over my notes from all of our old episodes. How fun. But I do have a few additional sources on salmonella paratyphi. I now want to read

the supplemental material for that one paper, because they did not read it. And I also have a couple of really great papers on the pathogenesis and the like molecular pathogenesis of all of the different viral hemorrhagic fevers. So if you want to read more about all of those. And then a bonus one on parvovirus, just as a teaser for a future episode. But you can find the list of our sources from this episode and all of our episodes on our website. This podcast will kill you.com under the episodes tab. Thank you to Bloodmobile for providing the music for this episode and all of our episodes. Thank you so much to Tom Brigh Fogel for the incredible audio mixing.

And thank you to you, listeners. We hope that you enjoyed this and learned something new. I know that I did, so I'm hoping that everyone else did and isn't just like, WTF did we even talk about in this episode? Right, write in your thoughts, please. Please. Do you want more of these? Because I bet there's more.

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