This Podcast Will Kill You - Ep 10 Yellow Fever: Is there a Hamilton song about this?

Episode Date: January 9, 2018

Today we're talking about yellow fever, a disease with a history as colorful as its name, and a vector as pretty as a picture (depending on whom you ask, I suppose). From an epidemic that decimated Memphis, Tennessee in the late 1800s, to the development of the vaccine, to where the offending mosquito hangs out today, we'll cover everything you need to know about this disease. Like for example did you know that A. Ham The Man himself was infected?! Yeah, me neither. Let's learn things together. See omnystudio.com/listener for privacy information.

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of hours. It's the AI native ERP from the makers of QuickBooks. Learn more at Intuit.com slash ERP. Yellow fever had a macabre way of toying with its victim before killing. For three days, there was fever and chills, followed by a marked improvement. The temperature fell. He could think if it pleased him to fantasize that the worst was past. Maybe he could tell himself it had been influenza, or perhaps a touch of malaria, or some unnamed tropical thing, of which there were many. But on the fourth day, yellow fever returned with a vengeance. Beads of sweat popped out on the victim's skin as the fever returned and climbed steadily to 103, 104, 105.

And then the chills came and the victim's teeth chattered and he begged for covers, only to kick them away again when the fever returned. Slowly, the patient's skin turned yellow, and patches of the inside of his mouth began to ooze blood. Nausea came and passed and returned. There was a pan by the bed to catch the black vomit, a mixture of blood and digestive juices. Two-thirds of the patients eventually recovered and became immune.

For those who didn't live, the jaundiced skin became yellower and yellower. The end was near when test detected that protein had begun to leak out of the blood through the kidney membranes and into the urine. Shortly after that, the kidney shut down and the flow of urine. and ceased. When the kidneys died, so did hope. The racking hiccups began. If the patient was lucky, he went into a coma at about that time. If he was not so fortunate, consciousness faded into delirium, and he screamed and cried out in his living nightmare until just before death, which usually occurred between the sixth and the ninth day. I have chills all over.

Me too. Oh my gosh. I hope they're not yellow fever chills. Oh, let's hope not. That's terrifying. I know. It's really, oh, it's horrific. Wow. Yeah. Well, if you've just joined us, you know you're listening to this podcast will kill you. Yes, you sure are. Welcome to episode 10. No. I know we're in the double digits now. Oh, that's exciting. It really is. Big milestone. What a way to start it off. I'm Aaron Welsh. And I'm Aaron Alman Updike. Thanks for joining us. Today we're talking. about yellow fever. You got it. And what do we have to drink today? What's our quarantining? What are we calling it, actually? Mellow yellow fever. Mellow yellow fever. It's essentially mellow yellow and vodka. You know, they can't all be winners, guys. I mean, we definitely don't think this is delicious, but the name was too good to pass up. It was. It just had to be done. It really did.

Mellow yellow fever. All right. Well, that was fun. That was fun. That was a quick intro. We just bang, bang, boomed it. I know. I think that we're, like, excited to get to the material.

Yeah, I think so, too. All right. Well, let's just get to it. Straight to the biology. Jump straight into it. Erin, tell me what you got. Okay. So, yellow fever is another RNA virus.

We've had a few of those. Like what else? Influenza was an RNA. A virus. Okay. Cool. There was another one, but I don't remember which one it was. One of our other viruses.

At some point, the facts begin to blur. They all mush together. Super bug. Super bug mush. This actually was, you'll probably talk about this, so I hope I'm not stepping on toes, but it was the first viral disease that was shown to be transmitted by mosquitoes. I don't really mention that, but hey. Well, then here we go.

I think that's really cool. Good old Walter Reed. Yeah. You'll learn WTG. Way to go. Oh. You will learn a lot more about Walter Reed in that whole situation. I'm excited about that. Yeah. So this is a virus that's transmitted by mosquito. I think our third vector-borne disease so far this season. Plague malaria. Plague malaria. And now this is pretty exciting. So it's transmitted by a skeeter. It's transmitted by a skeeter. That even if you've never heard of, and yellow fever. And now this is pretty exciting. So it's transmitted by a skeeter. It's transmitted by a skeeter. It's transmitted by a skeeter that even if you've never heard of, anything about mosquitoes, there's a good chance that you've heard of this mosquito because it also transmits dengue, chicken gunya, Zika virus, which is all over the news right now. So this is a pretty gnarly mosquito named 80's Egypti. Oh. Yeah. So there's also another, so 80s Egypti is called the yellow fever mosquito. So that's the common name for it. Oh, I didn't know that. Yeah,

that's a common name. There's another mosquito 80s alpictus that's also capable, and very commonly transmits this disease to humans. That's the tiger mosquito. Okay. So if you've ever heard of the tiger mosquito or the yellow fever mosquito, that's the mosquitoes we're talking about today. They're black and they have white stripes on them. They're actually cute as far as mosquitoes go.

What is the geographic distribution of those currently? And where do they come from? So I believe they come from Africa. Both do. I believe so. I should probably double-check that. 80s apple pictus might have come from. Asia because it's often called the Asian tiger mosquito. That one might have come from Asia.

But at this point, they're pretty well distributed throughout the tropics, and both of them are increasing in range. So 80s Egypti and 80s alpictas are both found in the southern United States in Florida and things like that. And they actually have been expanding. One of our lab mates has been doing research on the expanding distribution of these guys even into Illinois. Yeah, shout out to Allison Parker. Woo. Woo. Yeah. So they're kind of ubiquitous. throughout the tropics, which is one of the things I'll talk about later that makes yellow fever a scary disease to talk about is that the mosquitoes that transmit this exist in a lot of places, even where this virus doesn't exist currently. So there is a fear that this virus could then

spread to places that it isn't currently. Gotcha. Yeah. So similar to malaria, you get infected when a female mosquito bites you and injects her saliva into your bloodstream, and that saliva is full of these little viral particles. And 80s egypti, part of the reason that they're so gnarly and they transmit so many diseases to humans is that they're really well adapted to human habitats. They're what we call a container breeding mosquito. So in the quote unquote wild, they probably laid their eggs in tree holes, ephemeral ponds and things like that.

But in urban environments, they're really well adapted. They can use tires, flower pots, bird baths, anything that you have that holds water. gutters. Gutters. Shout out to Allison again. Yeah. So they're the main transmitter of yellow fever in what we call the urban cycle. So there's multiple cycles of yellow fever.

The urban cycle is exactly what it sounds like. It's when 80s Egypti transmits yellow fever between humans, so from human to mosquito to human, within an urban environment, like, say, Sao Paulo, Brazil, for example. Okay. Now, there's also what they call a silvatic. cycle and Silvatic just means wild. So this is also known as jungle yellow fever, which is essentially when you have different species of mosquitoes actually, a totally different genus in South America and another species of 80s in Africa, when you have virus circulating in monkeys and then you have

mosquitoes transmitting this yellow fever virus between monkeys and other non-human primates from monkey to monkey to monkey. and then they eventually might spill over into the human population. Okay. So like a spillover event instead of like in a city just like an urban human cycle. Right. Yeah. So this generally has sort of smaller outbreaks.

You can imagine that if a person got infected from a spillover event and went to an urban area that had 80s Egypti, it could result in a larger outbreak. Right. But yeah. So the sort of enzootic cycle, which just means the endemic cycle in animals, is really, really important in sustaining this yellow fever virus. And it's why the hope of ever sort of eradicating it is basically non-existent. Really? Yeah.

Because of this enzyatic cycle, it's almost impossible to imagine a situation in which we could eradicate yellow fever as a public health problem. Interesting. Yeah. Also, bummer. Yeah, bummer. I mean, from that earlier description, yeah. Yeah.

It would be really nice to never have to get it. anyone experience that. Yeah. There's also a third cycle that they call a savanna cycle or an intermediate cycle, which mostly happens in Africa, which is why they call it the savanna cycle, which essentially is when you have transmission between mosquitoes, non-human primates, and humans. And this happens with yet another species of mosquito. So it's basically just that rather than going from monkey to mosquito to monkey to mosquito

and occasionally spilling over into human, This is a more integrated cycle that kind of goes from non-human primate to mosquito to human to non-human primate. So if you imagine situations where you're maybe living in closer proximity to other non-human primates, that's when you might see a cycle like this. Okay. Yeah. Interesting. Yeah. And also importantly, before I start to talk really about the symptoms of this disease, the virus in this case can be vertically transmitted between mosquitoes.

And what that means, this is some deep. mosquito biology here. Yeah, but it's so important in the transmission. Yeah. A vertically transmitted infection means that female mosquitoes transmit the virus to her eggs. So then when those eggs hatch, larval mosquitoes are already infected with the yellow fever virus. And this is really important because that means that when they emerge as adults and are about to take their first blood meal, they can infect that first organism that they bite. Whereas with malaria and the a lot of other mosquito-borne diseases, the mosquito has to get infected by taking a blood meal first. And so what do we call that form of transmission?

That would be just horizontal transmission. Okay. Yeah. So, yeah, so this is super important in terms of viral transmission because you don't have to have that initial blood meal to infect the mosquito. They're potentially infectious right out of the gate, which is really important. You want to get to some? That is very scary, actually.

It's really scary, yeah. You have this like basically this pool of mosquitoes that can always be infected for generations and generations. They're just emerging infected basically. Yikes. Yeah. Yeah. Yeah. So, but I do want to get to some symptoms.

Let's do it. So yellow fever is one of a number of what we call viral hemorrhagic fevers. Ooh. Yep. It's as bad as it sounds. What are some of those other ones just as a quick? Dengue can be a hemorrhagic fever. You also have things that are not transmitted by mosquitoes like.

Marburg or NEPA, Ebola. Next episode. Right? Next one next. Second to next. Next next. That's not right. Yeah.

There's no word for that. The day after tomorrow episode. No. The episode after the next. Yes. The ultimate episode of this season. Oh my God. Yeah.

Wow. So yes. Those are some other viral hemorrhagic fevers. So here's how. things happen. When a person gets infected by the bite of a mosquito, they generally have about a three to six day incubation period. So not symptomatic. The virus is just in your body starting to replicate. Then, for most people, symptoms aren't that bad. You get fever, headache, back pain, chills, muscle pain, nausea, vomiting. Okay, it's pretty bad. That's terrible. So you're generally feeling really

crappy. And generally this lasts for about three to four days and then you recover. However, in about 15% of cases, which is actually kind of a lot. Yeah, absolutely. They say it's a small number, but that's not that small. No. Small number would be 0.001. Yeah. So about 15% of cases enter a second phase. They call it the toxic phase. It's the hemorrhagic phase. It's the gnarly that you're probably not going to recover from this phase. There's a 20 to 60% chance or higher that you won't recover. Wow. That you'll die.

By the way, that's what I mean by don't recover. Because those are your two options here. You end up with a fever that recurs. So you sort of get better from that first round like we heard in the firsthand account. You get better. And then all of a sudden your fever spikes again. Then you end up with jaundice, which is where we get the name yellow fever. your skin really turns yellow.

And this is because of how much damage the virus does to your liver. So if your liver stops functioning well, then it can't break down and recycle your red blood cells. So you end up with bilirubin in your blood, which literally turns your skin yellow. Wow. Yeah. So you can imagine that liver damage, like that's not a good thing. No. You need your liver.

You only got one of those. You only got the one. Then you can end up with bleeding from your eyes. eyes, your mouth, your GI tract, which then causes that bloody vomit that we heard about because of how much you're bleeding into your GI tract. So the Spanish name for yellow fever is actually Vomito Negro, which means black vomit. I didn't know that. I didn't either.

It's disgusting. Yeah. Yeah, your whole insides are bleeding, right? Your whole insides are just bleeding. There was something, like, in the early descriptions of the disease, doctor is showing a, you know, as per usual, lack of knowledge about women's health and other things that they said that it causes older women, like postmenopausal women, to spontaneously menstruate. Oh, Jesus.

When really it was just your uterus is bleeding because your whole body, everything is bleeding on the inside. So that's another horrifying symptom. Oh, God. That would also be terrifying. Can you imagine? I mean, the whole thing. Yeah. If you're even not delirious.

Right. Right. Yeah. Yep. So then we get even worse. You end up with kidney failure, which again, you really need your kidneys. Those are really important. Yeah. Your whole body is shutting down. Your whole body is shutting down. And that is how you end up with death is just organ failure. You also, the hiccups are a really common symptom, which I find so interesting. And hiccups are the worst. Oh my gosh. I think they're Brett's number one least favorite thing in the entire world. Yep. So. That is the toxic phase of yellow fever. The fatality rate, again, is 20 to 50% or higher. So that makes the overall fatality rate somewhere between 3 and 7.5% of everyone who gets infected with yellow fever. And that's based on modern estimates with, like, adequate care and for the most part. For the most part. Yeah.

And you die, it's fairly quickly. Most people, if they get to the stage of this severe illness, it's within 10 to 14 days, they're dead. Wow. And case fatality rates are generally lower in Africa than they are in South America, which are the two main areas where yellow fever is currently endemic, is Africa and South America. And some of this might have to do with strain differences in the virus itself

between Africa and South America, but there's also a lot to do with host factors like prior exposure and your individual immune response. And especially the lethality of that hepatic disease seems, to be very correlated to the viral load in your blood. So how much virus you actually have in your blood will determine whether or not you die from it once you get to that severe stage. Yeah, so that viral load in your blood is a factor of both the initial infection. So how many viral particles that mosquito spit into you and also your individual immune response. How good your body is it actually

squashing that infection? That's crazy. Yeah, so that's pretty much yellow fever. There's no treatment. Besides just like supportive therapy, you can try and, you know, prevent liver, complete liver failure and kidney failure with supportive therapy and things like that. So hospitalization is important if you have yellow fever to be able to monitor you and things like that. But there isn't any actual antivirals that are good at treating this. There is a vaccine, which is great. And I'll talk a lot more about it when I talk about what's going on with yellow fever today because the vaccine is really important. And if you survive, you're immune for life.

Hey, that's great. So that's great if you survive. If you survive. If you survive. Wow. Yeah. Well, I think that's all I have for the biology. Oh, is it my turn?

It's your turn. It's my turn. Teach me everything about the history. I can't wait. I can't wait either. Opening scene. The camera pans across to post-Civil War Memphis, Tennessee, USA. Late spring, 1878.

The city is bustling. full of shops, restaurants, frilly dresses. Lively music plays over the scene. Yes, the streets may smell like horse poop, but this is 1878. What city doesn't? Memphis is the place to be. As the heavy clouds gather over our picture of Memphis, you notice the streams and streets are already full to bursting with water.

The gentle hum of a mosquito sounds over the picture, soon joined by dozens, hundreds more. Cut to September of the same year. The contrast is shocking. A shot of deserted streets, empty storefronts, houses abandoned seemingly in the middle of a meal. Cannons fire in the distance. As the camera passes over the lonely streets to a graveyard on the edge of town, you are horrified to see bodies stacked, swollen and rotting in the summer heat. So many bodies, so little time. In the next scene, you come face to face with the manifestation of this horror, a person thrashing wildly in a bed stained with black vomit. while a doctor tries in vain to restrain his patient. You can almost feel the burning heat coming off of the skin of the poor victim,

and as the camera goes in for a close-up, you get a glimpse of the eyes darting back and forth frantically, their normal white color turned a bright, deadly yellow. Oh my God. I want that movie. Right? I want to see that movie. Yeah, I really want to, too.

Oh, that was amazing. I am there. Here we go. So, yeah, that is how I imagined the 1878 yellow fever epidemic in Memphis. Wow. Which this epidemic would end up being the deadliest yellow fever epidemic in U.S. history. Wow. Yeah.

I think a lot of people probably don't realize that yellow fever ever existed in the U.S., much less how serious it was. Oh, yeah. And you're going to, well, now you're going to learn. Yes. So before the epidemic, Memphis was the second biggest city in the south. Wow. hugely important in like trade, commerce, and culture, since it was next to the Mississippi River at the southwest corner of the state. However, its link to travel and trade came with a serious

downside. As we know by now, money and goods aren't the only things exchanged at port cities. Pathogens and parasites are just as happy to check out the next stop along the trade route, usually to the detriment of the town or city. Memphis had seen a few yellow fever epidemics in the 1800s, but none as devastating as the one in 1878. That year happened to be an El Nino year, which means that the ocean temperatures are warmer than usual, which then can really strongly affect global weather patterns. In El Nino year, certain areas get warmer and rainier, some get colder and drier. It just depends on where you are. Memphis, in El Nino years, gets hit with a ton of rain. Do you know who loves rain? Mosquito.

Yep, because that means there will be no shortage of breeding spots. Yeah. When in the summer, reports started pouring in of a possible yellow fever epidemic in New Orleans, Memphis remained unconcerned. Quote, we need not fear in Memphis, one contemporary newspaper said. We were never in as good a condition from a sanitary point of view. Famous last words. Right. Well, and of course, no one yet knew that yellow fever was transmitted by a mosquito, not bad air.

Oh. They're like, don't worry, we cleaned up our air, guys. It's going to be fine. Oh, everyone's dead. Everyone's, yep. Yeah. And so a quarantine was voted against. Wow.

Cool. One public health official who was really in favor of a quarantine resigned because he was like, this is going to be on my conscience forever that you guys are refusing a quarantine. WTG, guys. Yeah, no kidding. The first Memphis case was announced in August. Almost immediately, a mass exodus out of the city ensued. Whoa.

Anyone who could afford to pick up and go did. Wow. And though it probably saved many of the escapees, it was too late for others who died along the way. In the city, deaths ramped up to where about 200 people were dying every day. Oh my God. Houses containing dead bodies were identified by the overwhelming presence of flies. Oh! Some bodies weren't discovered until they were more than, quote, a lot of bones in a puddle of green water.

That's what was left of their bodies. Yes. Oh, my God. Just putrefaction. Just green water. If you have sensitive ears. Then why are you listening to this podcast? Right.

But here's where, here's some pretty horrifying descriptions. Okay, so fast forward like 30 seconds. Yeah. Go. Children were found sick in the same bed as their deceased parents. Oh, baby. And the worst thing that I read is that one mother was found dead beside a starving infant still trying to breastfeed.

Oh. Yeah. Oh, that's... It's really sad. Oh, my God. Dead bodies accumulated as willing and able, or even just living, grave diggers dwindled. One mass grave in Memphis still contains the bodies of 1,500.

yellow fever victims from this epidemic, unidentified. Oh, my God. During the peak of the crisis, the mayor wrote to the U.S. president, who was Rutherford Hayes, begging, pleading for assistance. The president's reply? No, thanks. Quote, I suspect the Memphis sorrow is greatly exaggerated by the panic-stricken people. We do all we can for their relief.

Oh, wow. The mayor tried one more time to secure aid before he took. became a victim of yellow fever. Sounds like DJT, bro. I was like, I think I wrote on my notes parallels to today in Puerto Rico. Yep, yeah. Yeah. It's not funny.

No, it's not funny. It's terrifying. I mean, we're laughing because we're just like in shock at how horrifying, yeah. Oh, my God. The virus finally burned itself out by mid-October. By that point, it had infected almost every person remaining in the city. That's amazing. Let's crunch some numbers.

Love numbers. Crunching. Before the epidemic hit, 45,000 people lived in Memphis. That's a good number. Yeah. Back then. About 19,000 stuck around for the duration of the epidemic. Oh, dear.

17,000 of those. 17,000 of 19,000 got yellow fever. Oh, my God. How many died? 5,150. Wow. So almost a third of those remaining. Wow.

It was this epidemic that prompted the U.S. to form the Yellow Fever Commission. Yeah. But before I get to that story, let's start at the very beginning. Yay! Okay, our story starts again, as it has before, in the forests of Central and Western Africa thousands of years ago. There, a virus was circulating, hiding out in the bodies of those horrible creatures known as mosquitoes. They're just trying to get by. I don't like mosquitoes.

Yeah. until one day it made the jump to primates hanging out in the trees. Once in its new host, it caused utter devastation, wiping out huge numbers of its mammal population until it couldn't be sustained. Then it disappeared for a while. The primate population grew and the virus was all but forgotten. But it would return and when it did, again, the primate population was destroyed and again the virus disappeared.

And this cycle would continue for thousands of years until one day the virus made its way into a new host, a human host. And what it did in human populations wouldn't be very different from the death and destruction in what it did in non-human primate populations. For generations, it ran through this epidemic cycle until it, in some ways, lost its punch. The humans that were continuously exposed to the virus grew in immunity until, in most cases, yellow fever was more of a childhood infection than the horrifying disease that would later be the cause of such fear and panic. Yeah. How do we know that yellow fever has its origins in Africa?

Well, first, African primates are pretty much resistant to the virus. Yeah. While New World primates, like in the Americas, are very susceptible. Yeah. In addition, Europeans and Native Americans were also super susceptible to the illness, resulting in death rates five to seven times higher than those in individuals born in Africa in historical outbreaks. Yeah. Any guesses as to how it got from Africa to the Americas?

Ooh, ooh, let me guess. Slave trade. You got it. Yeah. Or as one of the books I read called it, trans-oceanic shipping. Oh, my God. Yeah. Well, in, I think it was the WHO website or something.

It just said, like, it made its way to the Americas or something. Yeah. It didn't make its way. Okay. Yeah. Slave trade. Both virus and its mosquito host were brought. over during, yeah, during the slave trade, the mosquito would breed in small pockets of water

aboard ships and the virus circulated in the blood of the slaves that were brought over. Right. And the slave trade had really ramped up during the 17th and 18th centuries. And this is a common thread that we've seen. And I've talked about before. So basically European invasion, a lot of Native Americans died, which the Europeans viewed as their workforce dying. So then they had to go to Africa or they chose to go to Africa to.

to get slaves. So, but then them going to Africa means that they brought over things like malaria and yellow fever, which then killed even more Native Americans. I mean, it was just, yeah, lots of disease. Okay, back to yellow fever. I can't emphasize enough how much this disease gripped susceptible regions with fear and panic. It would be similar to the alarm over Ebola, except that yellow fever did actually cause epidemics in the Americas where Ebola hasn't yet.

Right. Before, yeah, thank goodness. Before the insane Memphis epidemic, one epidemic in particular stands out in a series of the 18th century epidemics. 1793 was once again an El Nino year. And Philadelphia was having a heck of a rainy summer. A heck of a rainy summer there, huh? Exactly.

And you know what that means. Muskeetures. Mm-hmm. At this time, the U.S. was in its infancy as a country, and Philadelphia was the new nation's temporary capital. Not anymore. Mm-hmm. It was also full of people and one of the more popular port cities. Soon after, ships containing refugees and slaves from the Caribbean docked in the harbor, reports of yellow fever began appearing.

Misguided public health officials decided that it meant that the disease wasn't import. it and that the rotting coffee and garbage down by the harbor were to blame. Oh, my God, people. I know, right. Myasma strikes again. Soon the numbers of infected were in the thousands, and the government effectively shut down. George Washington, John Adams, Thomas Jefferson, Alexander Hamilton, basically all of the founding fathers of the U.S. were witness to the fever, and Alexander Hamilton actually came down

with it. Really? And survived. A-ham. I don't know about the Hamilton musical. very much, even though it's like the most popular thing in the world right now. It's because we can't afford tickets because we're grad students. But if any of you listeners are big fans, I really want to know whether they talk about him getting yellow fever. Me too. Tell us. Let us know, please. I mean,

I could ask my mom. Yeah, you could. My parents went and saw it because they're cooler than me. So all in all, over 10% of the Philadelphia population of 40,000 died during the epidemic. So I have heard that yellow fever specifically was a large part of the reason that the capital ended up moving. Isn't that, is that the case? So, I mean, I did a little bit of research into this. And I don't know whether that's necessarily the case. Okay. So Washington, D.C. and the White House and that whole area was being built from like 1790 to

to 1800. Okay. And so I think that Philadelphia was chosen to be a temporary capital. But I do think it started out as being more or less the. U.S. capital. But I don't know if that was, if Yellowfebber was the reason it moved or if it was, you know, building was pushed forward more. Right. Yeah. Or something. Maybe a historian could tell us. Yeah. That would be great. Yeah. Switching gears a little. Yeah. Do you know what the Louisiana purchases? Yes, I've heard of it. Okay. That's thrilling. So basically, it's the deal that took place in

1803 where the U.S. bought a ton of land from the French. This land didn't just include Louisiana. Now, the land from the Louisiana purchase makes up 15 states. It was a huge change that totally impacted the future of the U.S. and expansion into the West. Big time. Without the Louisiana purchase, the history of the U.S. would be very, very different. Yeah. Now, did you also know that the reason for its existence can be traced in part to yellow fever?

Was it because, like, all the French people were dying of yellow fever and they're like, we want to get the hell out of here? Well, not so much. But it's a little bit similar. Okay, tell me it. So, yeah. I'm not good at guessing. So in the years leading up to the 1803 Louisiana purchase, France controlled a fair

bit of land both in what is now the U.S. and in many Caribbean countries. And in 1802, France and the U.S. almost went to war over some trading in taxation crap, which is actually interesting, but I don't want to go into because we have no time. This is a disease podcast. Yeah. Not a tax podcast or whatever. Uh, snooves. War was so close at hand that Thomas Jefferson, who was the U.S. president at the time, sent like 50,000 troops to New Orleans.

Wow. But they never had to fight. And they didn't have to fight because of yellow fever. Napoleon, who was at the time not Emperor Napoleon, was assembling troops in Western Haiti, which was a French colony, both to quell the recent slave uprisings in Haiti and to prepare to go to war. war with the U.S. He started with 20,000 troops. And when they started to die by the thousands due to yellow fever, he ordered 20,000 more. And he ordered more troops after his replacement troops died. Oh my God. In total, an estimated 3,000 troops were left alive at the end of this ordeal, with over 50,000 of their comrades killed by the illness. What? Holy heck. Yeah. It's insane.

obviously this left them powerless and humiliated. Yeah. And the few French that remained left Haiti, which became independent. And soon after, Napoleon signed away Louisiana, stating that he could in no way afford a campaign against the U.S. All because of yellow fever. Wow. Isn't that crazy? Yeah.

So cool. During the Civil War, soldiers died of yellow fever by the thousands, and this is where we see a particularly despicable act of attempted bio-warfare. I had to throw this in because this is just one of my favorite little tidbits. Tell me. I've never heard about bio-warfare with yellow fever. Dr. Luke

Pryor Blackburn of my home state, Kentucky. Kentucky. Earned his nickname Dr. Black Vomit. Oh. After sending soiled clothing of yellow fever victims to northern cities in an attempt to help the South

win the war. Oh my God. That's so misguided. Oh, wait. He also had plans to burn New York City to the ground and poison the water supply. But he wasn't done there. He tried his hand at assassination by packing up clothing and bedding again from yellow fever wards and shipping them to President Abraham Lincoln. Obviously, you didn't do anything. Check out these dirty clothes. They're covered a black vomit. See how that treats you. Oh, my God. Obviously, yeah, obviously it didn't do anything.

Well, but they had had no idea. They didn't know how, I mean, it worked so well with smallpox to kill off Native Americans. Yeah, he's like, that's a great idea. Let's do it again. Well, it also didn't do anything to hurt his career. Everyone was like, you're full of good ideas, man. Just keep trying. Just keep trying.

He later became governor of Kentucky. Oh, my God. Okay. So now let's pick up where I left off earlier. After what happened in Memphis and in response to the high death toll caused by the virus during the Spanish-American War, the Yellow Fever Commission was formed. Their goal to try, desperately, to find out what the cause of yellow fever was and to try and stop it. This four-person super team, based in Cuba, was made up of two army physicians, Walter Reed, whose name... You've heard.

You've heard. And James Carroll. And two civilian physicians, Jesse Lazier and Cuban-born Aristides. Agremonte. Jesse, is that a man or a woman? It's a man. Damn. I don't think women were allowed to practice medicine at the time.

Yeah. Besides bear children. Each of these men would come onto the project with their own unique personalities, sometimes clashing, sometimes complimentary, and their own preconceived notions about yellow fever. Jesse Luzier, who was an easygoing man devoted to his family, had a hunch that it could be the mosquito, a theory originated by a Cuban researcher named Carlos Finlay.

as per usual finlay's early work supporting this theory was ignored by the research community but he kept going thank goodness and so when jessie lazier approached him about it he was delighted and helped by sharing his data in samples he was just like great yeah i'm totally down to help and collaborate super cool that's awesome all lizir had to do was design an experiment this was the late 1800s so he went with human experimentation that's what you do naturally yeah He fed mosquitoes on a yellow fever patient, collected them, and then had them feed on unexposed people. Oh, God. Fortunately for them, and unfortunately for the commission, no one became infected. Lazier was a touch disheartened by this, but kept at it. In order to have a research colony of mosquitoes, you have to keep them fed. And while today, there exists really cool contraptions for mosquito feeding.

Back in the day, you were their meal. A lot of people still do that. Yeah, it's true. It's like easier and faster and just like, well, here you go. Here's my arm. Sounds horrible. We don't study mosquitoes. No, I don't have to keep my ticks alive.

I just kill them. Me neither. About 12 days after this first failed experiment, Carol, who is another member of the commission, stopped by the lab to see how things were going. Lizar asked him, hey, you wouldn't mind offering up your arm. one of these mosquitoes hasn't been fed in a while. Carol was like, yeah, sure. He probably viewed it as low risk.

It had been a long time since the mosquito had fed on a yellow fever patient, and Carol didn't believe too strongly in the mosquito-borne idea anyway. Guess what? He became the first experimentally infected person for the commission. Wow. After days of high fevers, delusion, and racking pain, he survived. Wow. Yeah.

But the infection would influence. prepare his health for the rest of his life. Wow. Lizier was horrified that he had done this to his friend and collaborator. But thrilled. But like, also what was he expecting? Yeah. Was he also like, oh, I'm so sorry that you got sick, but also, yes, I was right.

Yeah, I think he was a bit encouraged at this point. And he kept at the experimentation until the U.S. was finally like, hey man, you've got to stop experimenting on people. We're not doing this anymore. He's like, I told you so, guys. I told you so. He was like, are you kidding me? Fine. Fine. Fine.

Wink, wink, nudge. Yeah. And in his lab notebook, where he kept track of every person who had been fed on by an infected mosquito, one final entry noted that, quote, guinea pig number one was fed on. Every other person who he had kept track of in his journal had their name and information. But then he had guinea pig. Interesting. But it wasn't an actual guinea pig, was it?

No. It was a human. We don't know who this guinea pig was. Interesting. But many believe. it was Lazier himself. Huh. It wouldn't be the first time he had intentionally exposed himself to the virus,

but it would be the last. After days of battling the infection, oh. He succumbed. Oh. He never got a chance to see his wife, son, or newborn daughter again, whom he had sent home during a yellow fever outbreak month before. Oh, that's sad.

It's really sad. What a way to go. I know. And though his death did convince many that mosquitoes were the vessel for the virus, It wasn't airtight science. After all, we don't know that he was guinea pig number one for sure. Right. And no one could say that conclusively because if he had intentionally exposed himself

after the U.S. had handed down this order to not do it anymore, his wife and kids would be left with no, like... Because he violated orders? Not because he violated orders, because it would have appeared as suicide. Oh. And if you... So like the health insurance or the life insurance policy, Oh, interesting.

It would have been nulled or nullified. Whoa. Yeah. That's, I guess, why he didn't write his name down. Yeah. That would be evidence to point to that it was him. Mm-hmm. Interesting.

Yeah. What a crazy person, though. Why would he do that? He felt so close to proving that mosquitoes were the vector for yellow fever. Wow. He was just, you know, too passionate about science. I guess. Not me.

So yeah, even though he died after being bitten by, well, after we assume being bitten by the infected mosquito, it wasn't conclusive. And so more experiments would be needed with more human volunteers, which did actually continue to happen strangely. Weird. I will say that in these later experiments, the mortality rate in those infected was zero or very close to it. Eventually, the mosquito was accepted as the transmitter of yellow fever. Cool. And this knowledge was used in control strategies like the ones I talked about with malaria and the Panama Canal and so on. Yeah.

Even though there was the knowledge necessary to get rid of the mosquito, the world needed a more permanent solution. Yeah. The yellow fever vaccine was developed by Max Thaler in the 1930s and was deployed globally in a massive vaccination campaign. Thaler, by the way, would be the only yellow fever Nobel Prize winner. After these vaccination campaigns ended, the disease picked up speed. causing more and more infections, particularly in African countries, during the 50s through the 90s. During the 1960 to 1962 epidemic in Ethiopia, about 100,000 people were infected, and 30,000 died. Wow, that's a 30% mortality rate.

Yeah, and that was in a population of 1 million. Wow. So 10% got infected. And others infected, 30% died. Oh, my gosh. And that's where I hand it off to you. Oh, my goodness. Tell me about yellow fever today.

Okay. So yellow fever today, it's either considered endemic or important, meaning there's outbreaks and things like that, in 34 countries in Africa and 13 countries in Central and South America. Okay. Mostly just South America. As far as I can tell in Central America, it's just half of Panama. That's it for Central America.

Which half of Panama? The eastern half. The dairy inside? Yeah, exactly. And it's really just in the Dorian. Okay. In 2017 so far, there have been outbreaks or reports of outbreaks in Nigeria, Brazil, French Guyana, and Suriname.

And in 2016, there were reports from Angola, the Democratic Republic of Congo. There were actually several cases in China, but they were all imported from Angola. Oh, okay. Yeah. So case reports really very wildly from year to year. and I think that part of the reason is that surveillance is just really not good for this disease. Why do you think that is? I don't know.

And I've had a really hard time trying to figure out why it's so difficult to get hard numbers on how many people are getting infected with yellow fever every year. Because it's endemic in a lot of the same places as malaria. Yeah. And WHO is like, we have this yellow fever task force, blah, blah, blah, where they're putting out, like, they're trying to get everyone vaccinated. And I would think if you're trying to get everyone vaccinated, you know how many people are getting infected. But the most recent numbers that I found were from 2013, where they were estimating that between 84 and 170,000 people came down with the severe form of yellow fever in Africa alone. Oh, can you say this numbers again? Yeah. 84 to 170,000. Wow.

The severe, like black vomit. Exactly. And of those, there were between 29,000 and 60,000 deaths. That's a really high mortality rate. High mortality. Yeah. And it's a lot of people. Yeah.

And it's a huge range, which means we really don't know. And it's estimated that the actual number of cases are anywhere from 10 to 200. 250 times higher. I'm sorry. 250 times? 250 times. Okay. And I think that my guess is that a large part of this is that we really only hear about the severe cases.

And remember that that's usually only about 15% of cases that end up with that severe form. Because a mild form of this disease, you're either not going to go to the doctor at all or you, well, really, you're just probably not going to go to the doctor at all. So you're never going to get report. poured it on, essentially. You're just going to assume it was influenza or malaria or dengue or whatever, right? Yeah. It's just so interesting to me that this one, like malaria, I don't know, like why we have such terrible, terrible estimates for it. And I didn't think, I mean, I thought that especially because it's vaccine preventable, there would, I would just be able to Google, beep, boop, pop. Right. Vaccine, how many people get yellow fever. But no, I can't.

find that information it was really, if someone knows that where to find it that I'm just not finding, please let us know. A better resource that would be, yeah. It's not, there are not great hard numbers out there. Yeah. But there are definitely outbreaks that happen every year. And so there's, you know, information on specific outbreaks. Like there's one going on in Brazil. It's mostly seems to be over at this point. It was really from like July to October where there was about 70 cases that they suspected might be yellow fever. Only two of them have so far tested as positive for yellow fever. Interesting.

And so a lot of, especially in South America, a lot of the surveillance is actually done on monkey populations. So they keep track or they try to keep track of any what they call epizzootics or outbreaks in animal populations. Okay. So for example, there's been at least 120 cases this year so far. Brazil that have been confirmed of yellow fever in non-human primates. Oh, okay.

So that's when you can end up with then spillover from those non-human primate populations into humans. Yeah. And one thing that's really important to talk about yellow fever today is the information that this 80s Egypti and 80s alpictus, these mosquitoes are everywhere. Right. I mean, basically everywhere. and their ranges are expanding.

And this is why we've seen outbreaks of things like Zika and Chikungunya recently in places that they never existed before is because if you introduce an infected person, a human who's infected with this virus into a new environment, all it takes is one single mosquito to basically start a brand new epidemic. Because remember, mosquitoes are transmitting this virus vertically to their offspring. So it really just takes one. Yeah, that's really scary. It's really scary. So currently, yellow fever isn't a problem in Asia.

It never has been. For some reason, people really aren't quite sure why it hasn't been a bigger problem there because you do have dengue and things like that. So it's kind of a mystery as to why we haven't seen yellow fever outbreaks there, the way we've seen them in South America and Africa. Interesting. Yeah. You definitely have 80s mosquitoes.

there. You have dengue infection, so you have mosquitoes that are capable of transmitting this virus. So you're kind of already ready to go on that front. So the introduction of an infected person could be really devastating because the population of humans is totally naive, presumably. And to a certain extent, you have seen things like this happen, where you've had migration of transmission into, for example, Amazonian regions of Peru from more coastal regions. Okay. And things like that. So, Yeah, it's kind of, on that front, it's really scary. The potential for this to become a much more widespread disease definitely exists.

So a lot of countries actually require that you show proof of immunization for yellow fever if you show that you've been traveling to any areas that are considered endemic for yellow fever. This is like the yellow card, the transport card. Yeah, that yellow, yellow fever card. Yeah, we've been vaccinated. Yes. Thank goodness. Yeah.

Because I don't want to get yellow fever. So one of the other big problems besides globalization that's affecting yellow fever distribution is deforestation. So as humans are further encroaching onto forested areas, they're exposing themselves more to the sylvatic cycle of the disease by coming into closer contact with animals and the silvatic mosquitoes that usually feed on these animals. And this is true in both Africa, but also especially in South America where that endzootic cycle is definitely occurring.

Okay. That's, man. Yeah. Stop cutting down trees, people. Right? Your life depends on it. Yeah. And the good news is that there is this vaccine.

And the vaccine is pretty awesome. Yeah. It's an tenuated vaccine, so it's a live virus. And there's at least about 10% of children for whom it doesn't seem to work, so they need to get boosters. I'm not entirely sure why it is, but for some kids, it just doesn't quite work that well. It doesn't provide long-lasting immunity. But recent studies have shown that especially for adults, this vaccine provides extremely long-lasting immunity to the point where they're no longer even recommending booster shots for adults. Wow.

Yeah. The immunity is really great from this vaccine. That's awesome. Yeah. The problem is how to get this vaccine delivered to everyone in endemic areas. So that's a problem for so many things. Yeah, but I mean, I guess the thing is, like malaria, we can definitely see how difficult it is to control and monitor and get the drugs out. And there is no malaria vaccine.

Right. But for something like yellow fever, when you can vaccinate a population, I guess, you know, since you can't eradicate it from the environment, there are still going to be a susceptible pocket. Exactly. There's still going to be, I think, low levels. of transmission. Right. Because of that endootic cycle. It just seems so high.

Those numbers seem so high, though. Yeah. I mean, they are because not everyone is vaccinated. Yeah. There's also issues with your immune status at the time that you get the vaccine is really important. So if you have like a compromised immune system, whether from HIV infection or malnutrition, which is a problem in a lot of areas where this is endemic, then the evidence is still

out on how effective the vaccine actually is. Okay. But there have been quite a lot of mass vaccination campaigns, especially in Africa. I think WHO estimates that they vaccinated over 105 million people in the last few years in Africa, which is pretty great. It's also important to note that while very rare, there is the possibility of what's called vaccine-associated viscerotropic. And that's a big word. Disease. It basically means that you can get a disease very.

similar to regular yellow fever from the vaccine. That's not yellow fever. It is, it is yellow fever, but so the vaccine is derived from a specific strain of yellow fever and has been attenuated to be even less virulent. But for some reason, in a small, a very small number of cases, like 0.4 per 100,000 people. Oh, it's very small. It's very small. You get this disease that is essentially looks just like normal yellow fever.

Okay. And it can be really devastating. it has a fatality rate of about 63%. So it's really bad. Whoa. Yeah. But again, there was only about 65 cases of that between 2001 and 2011. Oh, okay.

So it's pretty low. I just, you know, it exists. Yeah. So overall, how scared do you need to be? I'd say keep your eye on it. Because of globalization, global travel, urbanization and deforestation. Climate change. So climate change.

There's a real possibility that we could see expansion of or changes in the range of yellow fever. And it's hard to say for sure that current vaccine stockpiles will be enough to prevent epidemics. Because when an outbreak happens, you need to have vaccination, like ring vaccination around all the people or around the whole area where you have an outbreak of at least 80 to 90% of people. And that's really high coverage that you would need for everyone to. to be vaccinated in order to prevent spread. But, I mean, this vaccine does exist and it's really great. Yeah, that is good. So there's a vaccine.

There's a vaccine. So if we could just get that vaccine to every person who's living in endemic areas, then we really wouldn't have to worry too much about yellow fever. Yeah. And nor would they. Nor would they, exactly. So, yeah. So that's yellow fever.

I think that's yellow fever. That was a really interesting one. It was. It has a... Yellow fever is kind of one that's just kind of like goes under the radar a bit. Yeah. I think because there is a vaccine for it, people kind of forget about it. Like, oh, we don't need to worry about yellow fever.

There's a vaccine. But like, not everyone has gotten a vaccine. Yeah, clearly it's still causing a lot of problems. Right. Well, should we cite ourselves? Let's cite our citation sources. I've got a few books. here. The American Plague by Molly Caldwell-Crosby is really great. And this focus is mainly on the

Memphis epidemic in 1878 and the formation of the Yellow Fever Commission, which, yeah, and she just does a really good job telling these stories. It's a historical narrative. Yeah. And so it reads really well. I really enjoyed it. That was one of the first disease books I read for fun. Me too. Yeah. The other one is called Viruses Plagues and History by Michael B. Oldstone. And yeah, it's a really good overview. And I didn't read this this time, but as a kid, I read a young adult book called Fever, 1793 by Lori Halse Anderson. And it's about the 1793 Philadelphia epidemic of yellow fever. I remember loving it as a kid.

I put it on the book list as a, hey, you guys should read this. You should read this. We forgot to cite also where that first-hand account came from. Right. I was thinking about that. I realized. Whoops. So that came from a book called Guinea Pig Doctors, the Drama of Medical Research

Through Self-Experimentation by John Franklin and John Sutherland. Cool. Cool. And then I also have to cite a couple of articles that were really interesting to read about the biology, especially of yellow fever. One is called Yellow Fever. No. By Moneth and Vasconellos in 2014.

And the other called efficacy and duration of immunity after yellow fever vaccination, systematic review on the need for a booster every 10 years by Gotuzzo at all 2013. And we have a book list that we will be posting. It's on our Facebook page. It's on our website. This podcast will kill you. podbean.com. So if you ever want to find these articles and books, you can go there and find them there. We'll also post the books and articles for every episode that we do when the episode

comes out. We've got a good reads list. Yeah, there are a lot of different resources, but we, yeah, we want you guys to read because reading's fun. Thanks to Bloodmobile for providing the music for this episode and all of our episodes. Thanks for listening, everybody. Rate review and subscribe. Now wash your hands. Filthy animals. Success starts with your drive, and American Public University is here to fuel it.

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