This Podcast Will Kill You - Ep 8 ABRACADABRA - Go Away Malaria!

Episode Date: December 19, 2017

It's both a disease of dinosaurs and a plague of people. A gin and tonic might make you forget how much those bites itch, but it won't protect you much from this mosquito-borne monster. That's right people, today we're talking about malaria! We're super excited to tell you about this parasite since it's one of EAU's personal favs (are we allowed to have favorite horrible diseases?). Come along as we travel back millions of years to explore malaria's wee beginnings, trace its path as it shaped human evolution, take a short botanical detour to make that G & T, and end up where we first began--in 2017. Turns out that monster hasn't released humanity from its clutches quite yet. See omnystudio.com/listener for privacy information.

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This is a job for Indeed sponsored jobs. Hey. How's it going? It's going well. I just made it back home and I practically prepared a, uh, the genitonic, a genitonic with a lemon. We'll accept it. So for this episode, we decided to sit down with our good friend Umat to ask him about his personal experiences with malaria.

I'm Umat Somji. I grew up in Nairobi, Kenya. Right now I'm a graduate student at the University of Florida, Gainesville. And I met Aaron and Aaron in Gamboa of Panama while we were doing fieldwork. at this tropical research station. I remember I had just come from a camping trip in West in Kenya, and I'd been back in Nairobi where I lived and my parents lived for about two weeks. One day I was just feeling really lethargic and tired, and I had this lower back pain.

That was really memorable, like this pain in my lower back. And I went to bed, and in the morning, you know, I was confused. I had a fever. I was really sick. My body hurt a lot. So I remember just having like really weird, wacky dreams, you know, and having these high fevers. And so I went, my parents took me to the, to the doctors. And I got a blood test, living in the tropics. There's a lot of different things that you could get. Of course, they did the malaria test and they did find malaria. But I had these very cyclical fevers, I would get really, really cold and suddenly I'd be really, really hot again. And I remember when I had the fever, when I was feeling really cold, I would be shivering so much

that my muscles would contract so much that they'd be hurting. And I went for another blood test because my mom was suspicious that this actually might be malaria. And still, there was no positive malaria diagnosis. But then my mom took me to the hospital at 2A. And I didn't know what was happening. I didn't know why we were going to the hospital in the middle of the night. And I got a blood test done at that time, and they diagnosed me with malaria.

And I didn't learn until later that it's really common for malaria not to be in your peripheral bloodstream until the middle of the night. So, yeah, that was kind of an interesting experience. I feel like malaria was such a big part of life growing up in Kenya. It was, I feel like it was the kind of the disease that whenever somebody had a fever or any sort of sickness, you'd always wonder, like, is it malaria? Because it could be, you know, it's really common there. So when you're really young, you learn about the Ennopolis mosquito. So, like, I remember in primary school, growing up, we learned about Anopolis and what it looked like when it was resting. this very unique posture when it's resting, and you can recognize it immediately.

And it's something that, you know, everybody learns in school from a really young age. When I was really young, you know how as a stereotype, every, like, young kid hates to have the chore of doing their beds, just like any kids I hated doing my bed. But there was something else I had to do. I had to, you know, fold up and roll up my mosquito net every day. And every night I had to unroll it. and, you know, tuck it around my bed so I could go to sleep for the night. And, you know, I hated doing it.

It's a chore and it's this extra thing you have to do, and I would do it badly sometimes. And I remember lots of times my parents waking me up, and I, you know, I had gone to sleep a rebellious teenager, not putting my mosquito net on. I was the worst, yeah. And, you know, I'd be like, okay, fine, I'll do it. That is the most beautiful introduction I've ever asked for this episode. Absolutely. It was like textbook perfection. Oh, really? Okay.

So thank you for going through that experience. So that was incredible. Amazing. Thank you so much, Umat, for sharing your story about malaria. And, um, wow. Hi, and welcome to episode eight. Holy crap. Holy crap.

Of this podcast, We'll kill you. I'm Aaron Welsh. And I'm Aaron Alman Updike. Thanks for joining us. We're very excited. This week we're talking about malaria. Yep. Which is a big one.

Mm-hmm. Totally. We're going to have a good time today. It's going to be really fun. I'm thrilled about it. Malaria is fascinating. It's a really, it's actually one of the first diseases that made me want to study disease. Oh, I didn't know that.

Yeah, malaria and schistosomyasis. Oh. They're like very close to my heart. That's so cool. Yeah. I'm excited about it. Learn something new about you. Right? But before we jump in, we have a correction to make.

We always say, if we get something wrong, please let us know. And this is proof that we're not lying. All of this is outside of our area of expertise. We expect to get things wrong. So in the very first episode, eight whole weeks ago at this point, I know, right? We talked about influenza, and I, mistakenly, said that influenza was a wrong. retrovirus. That is incorrect. Thank you, Dustin, for letting us know that. Yeah, thank you. But anyways, that's our correction. Influenza is an RNA virus, but it is not a retrovirus. So if you have a

correction for us, you can go ahead and send that to this podcast will kill you at gmail.com, or you can message us on any of our social media profiles as well. Yeah. That is all. All right. That means that we're on to quarantinis. What are we drinking this week? This week is the fever reliever. Wonderful. And what is in the fever reliever? Well, since we're talking about malaria today, we're drinking basically a gin and tonic. Okay.

And when I say basically, I mean, it's a gin and tonic, people. With a lime. Yes. All right. And we're going to get into why that has anything to do with malaria later on in the episode. So stay tuned. So tonic water has quinine in it. Yeah.

It won't be any sort of a. effective dose, but... No, no. Just enough to be delicious. Chiaz. Chiaz. Chiaz. Yes, with a British accent for many raisins.

Chiaz. Delicious. Gin and tonics were, when I was living in Panama, they were my drink. Too bad that you weren't living in an area of Panama where malaria was a real risk factor. I don't think that's too bad. Self-medicated. I'm pretty okay with that fact. All right.

Cool. So now that we've got our quorum. quarantini's underway, we're going to delve right into the biology. Erin, tell me about malaria. I will try my best. Malaria is a big one. And one of the things that makes malaria so interesting is the fact that it has a really complex life cycle, which means it's going to be complex to talk about today.

But we're going to simplify it as much as possible. Yes. So malaria is caused by a parasite. This is the first disease that we're talking about on this show that's caused by a parasite. Can you explain to me the difference between a parasite and a pathogen? Yes. So we usually use the word pathogen to refer to viral and bacterial diseases. Okay.

A parasite is usually referred to only for what are called protozoans or like parasitic worms and things. Okay. And protozoans are not bacteria. Right. So protozoa, it's not a great choice. term, but it essentially means it's still a single-celled organism, but it's much larger than a bacteria or a virus, and it's more closely related to plants and animals than it is to bacteria. So a little more complex.

Exactly, yeah. So malaria is a protozoa. All right. There are several different species of parasite that cause malaria. The one that causes the worst disease in humans and is the most widespread is called plasmodium falciperum. This is the species that's the most common throughout most of Africa, and it replicates really quickly so it causes a very severe form of disease. The other species are Plasmodium Vivax, which is the most common species in Asia, and it, along with another species called Plasmodium Ovali, have these dormant stages that kind of hang out in your liver for a long period of time where they're not really causing any active infection, not really causing any real simples, but they can just hang out there and then reemerge later in your life, like months or years later. Which is important also in the distribution for the mosquito and the seasonality of this because something like falcipram has to occur where the species occurs year round. Right.

The mosquito species occurs year round. Yeah. Whereas something like VyVax can exist in a place that has more seasonality to it in terms of cold and warm. Yeah, definitely. And then finally there is plasmodium malaria, which is found pretty much. worldwide and causes the most chronic infection if untreated. I should also note that there are other species of malaria that infect other mammals as well as birds.

Avian malaria is actually really important and is a major cause of decline of native bird populations in Hawaii and other places, but unfortunately we don't have the time to talk about those today. Maybe we could have a future episode on avian malaria? Yeah. Anyways, let's talk about the life cycle, shall we? Let's do it. So malaria infection starts when an infected female mosquito, put my entomologist hat on here,

because it's only female mosquitoes that bite you and suck your blood. Male mosquitoes just drink nectar. They're just little beat bops. Okay. So an infected female mosquito takes a blood meal, meaning sticks her snout into you and sucks your blood. And as she does this, the parasites, which are in her salivary glands, are injected into your bloodstream. These parasites, which look kind of like little spores, they're just little balls at this point, once in your blood will infect your red blood cells, or in some cases they'll travel through

your bloodstream to your liver and infect your liver cells directly. Then once inside of your cells, the parasites begin to replicate. They replicate and replicate and eventually explode out of your blood cells, and they'll fly freely through your bloodstream again. Uh-oh. And this is what's actually causing the symptoms that we see in. malaria is when these thousands of millions of parasites explode open your red blood cells and then travel through your blood to find new cells to infect. So now these parasites are free-floating in your

bloodstream and they can be picked up by another mosquito as it feeds on you. Then within the mosquito, the parasites have to travel through the mosquito's gut, survive through the stomach, replicate, reproduce, then they have to exit the gut, which isn't easy to do, because they're basically punching through the gut wall of this mosquito. Then they have to travel to the salivary glands where they can then get ready to start the cycle all over again. All this tells me is that I'm amazed that this is a real thing. Like it's so cool. The way it's so complex, how long it took for this to evolve.

Right. Such a complex life cycle. It's such. This is what I love about vector-borne diseases is how much more complex. this becomes because you have this entire other organism and there is a part of this life cycle of this parasite that takes place only in the mosquito and is dependent on that mosquito. All players have to be there. Exactly.

Cool. Yeah. So transmission of malaria isn't direct person to person. It happens just from the bite of this infected mosquito. Specifically, it's an anophilies mosquito. There are several hundred species, but only about 30 or 40, that are important in terms of human malaria transmission. and there's some evidence that once a mosquito is infected with malaria,

like once these parasites are in the salivary glands and ready to infect a human, mosquitoes are more attracted to hosts, more persistent in their attempts to feed, and they feed on more hosts per feeding attempt, which is crazy, because it's basically the malaria parasite going, hey, I'm here, I'm ready to go, better take a meal, better take a meal, better take a meal. That's super cool. it's host manipulation by a parasite. Yeah, it's crazy.

That's one of my favorite themes, I guess, or like favorite things. And yeah, like the zombie fungus. Maybe we'll do an episode on cordyceps. Definitely. Cool. No question we have to. Okay. Sorry to interrupt.

No, you're fine. One thing I think that's really interesting about this, and I'll talk more about it later on, is just that in terms of thinking about prevention of malaria, on the one hand, it makes it a lot harder to deal with prevention, when you have an entire other species that you're trying to deal with. But it also means that there's a lot of stages of the malaria parasite that you could potentially target that are outside of the human, which I think is really interesting.

So I'll talk more about that when we talk about the status of malaria in the world today. What else about malaria? So the incubation period, which again is the time from when you're infected to when you show symptoms, in this case from when you're bit by a mosquito and until you have your first round of symptoms is between seven and 30 days. And this large range depends on the species of parasite that you're infected with. So plasmodium falsiparum, the one that's sort of the worst, has the shortest incubation period, while plasmodium malaria has the longest.

That would make sense because you said felsipram replicate so quickly? Exactly. So in some cases, because you can have this really long incubation period, diagnosis and treatment can be somewhat harder, especially for example, if you're traveling or you become infected while you're traveling and you come back to a country where malaria maybe isn't very common, it can be really difficult to diagnose because it might be several weeks or months until you actually have any symptoms. That makes sense. Yeah. So malaria is inside you. You've been bitten by a mosquito that has injected a bunch of parasites. What's my body going to do?

Well, first, there's something that's called classic malaria, which has a cold stage with shivering, feeling very cold, a hot stage where you have fever, headaches, vomiting, young children can have seizures, and then a sweating stage where you just sweat a lot. But I don't know why they call it classic malaria because apparently this is a very rare presentation. Like it doesn't usually happen this way. Really? Yeah, I don't know if maybe this is, so maybe people have written about malaria in this way a lot, and that's why. it's called classic. But realistically, what happens is all at once you have fever, chills, sweats, headaches, nausea, vomiting, body aches, you feel like absolute human garbage. Human garbage.

And this happens in cycles. A classic attack lasts for between six and ten hours and happens every two to three days depending on the parasite species. So plasmodium falciperum replicates every two days. days, as does Vivax and Ovali, whereas malaria replicates every three days. So that means that in yourselves, they're basically taking two days to have a full cycle of replication, and then they're bursting out of your cells. Okay. And so that is how you end up with these fever and headaches, is all of these parasites all at once are bursting out of your cells and into your bloodstream. So each time you have this intense spike in all these symptoms, it's in response to the parasite

reproducing. Exactly. And that is also when you're going to you, you're going to be most infective for mosquitoes because that's when these stages that are infected to the mosquito are free-floating in your bloodstream as well. Okay, that makes sense. Yeah. So that's most of what you need to know, I think, about malaria biology. One thing that makes it difficult to control also is that diagnosis is really difficult. So typically it's done by microscopy.

So you need a person who's very highly trained to actually take a smear of your blood on a microscope and look through it. And it's effective, but you have to have people that are very well trained and even very well trained people. Because you have these cycles, if you just take blood at the wrong time, you might not see them or you might see things that look like malaria but aren't actually malaria. So basically, microscopy is imperfect. There are other molecular methods that you can use for detection of malaria, but they're

also not perfect. And in many cases, they're expensive. and sometimes cost prohibitive. But yeah, I think that's it for malaria biology. Okay. So do you want to hear about the history of malaria? Oh, I'm really excited about it. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again.

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That's got to be, that's the first time we've talked about millions of years on this episode show. It probably is. Malaria's history is, yeah, it's enormous. And we're going to get through it all. Yes. In the next 10 minutes. No. Uh-oh.

Well, first we're going to go back to the dinosaurs. Okay. And malaria's evolutionary origins. then I'm going to talk malaria before treatments were discovered. Then Panama Canal time. Yes. Just a little bit. And the failed eradication campaigns of the 20th century.

I'm thrilled. Let's do this. Give it to me. Malaria is an ancient, ancient disease. Definitely prehistoric. Some researchers think that the parasite evolved from a free-living plant species. A plant species? Yeah, like algae or something.

Yeah, so it has a bunch of genetic fragments that are similar. to those used to make chlorophyll. What? Yeah. That's so cool. I never knew that. It's very strange. I just assume that everything is like an animal because I'm, oh, what does Matt call it?

I have plant blindness. Yeah, you do. I think we both do. Yeah, definitely. A lot of disease ecologists have plant blindness. Definitely. Okay. Anyway, so in prehistoric times, I'm talking like Time of the Dinosaurs Prehistoric.

The ancestor of malaria made the jump from plant species to parasite. Scientists have found the DNA of a malaria species in a biting midge, which is an insect, preserved an amber from 100 million years ago. Stop it. Yeah. That's thrilling. Like Jurassic Park style. No, that's really Jurassic Park.

Oh, yeah. Oh, that's so cool. So long, long, long before malaria became a parasite of humans, it was probably a parasite of dinosaurs. Oh, my God. Which makes sense, considering that there are malaria parasites in so many different groups of animals today, including birds and reptiles. Okay, but we know that modern malaria is transmitted by mosquitoes, not biting midges, so when did that happen?

Probably around 30 million years ago. Eventually, it became a parasite of humans maybe 8 million years ago. Wow. Or ancestors of humans. Maybe 15,000 years ago, I mean, there's a lot of debate. Everyone's like, maybe then. Well, maybe in the year that I study. Plus or minus, 8 million years.

In any case, once it was in humans, it never really left. Ever since malaria emerged as a human parasite, it has infected and killed billions. That's with a bee. That's with a bee. Of people throughout history. Oh, man. It doesn't really have the same wham, like epidemic storyline that some of these other diseases that we've talked about have. Dinosaurs are a pretty big wham, though.

Oh, yeah, absolutely. But, like, you know, in terms of a pandemic or an epidemic. Right. But the numbers are still absolutely staggering, both in ancient and in modern times. Are you ready for the body count? Malaria probably killed half. 50% of all of the humans who have ever lived. What?

About 108 billion people have existed at some point or another throughout history. That means that malaria has probably killed about 54 billion. million of them. What on earth does that even? You can't even? I can't, I literally, can't even. Okay. You didn't know we were millennials before. You know now, but also. So, that number seemed really outrageous. Also, it's just too, it's too much. It's you can't wrap your brain around it, all those things. Yeah. But I was like, all right, that seems, wait, let's hold on a second. Let's take a step back. It's got to be someone exaggerating. I saw. that and I was like, oh, I really want to put that in the podcast. And I was like, I don't know,

that seems a little bit bogus. I looked into it. Yeah. And it may be on the upper end of things, but it seems certainly possible. There's obviously, yeah. There's, well, I don't know if you can make a confidence interval with this type of, you know, back of the cuff calculation. But it is possible. Wow. It's insane. That is really a cool statistic. Now, that's the kind of thing you want to whip out at a party. Yes. Like, hi, nice to meet you. Did you know?

Only whip out statistics. This is why I have so many friends. Okay, so I don't really have an estimate for when malaria first popped up in humans. The reality is that malaria has been with us throughout our evolutionary history and actually plays a pretty big role in it. As we all know, the cradle of human evolution is in Africa, so it's also likely that that is also where malaria evolved. As you mentioned, malaria is caused by several different species of organisms. I'm going to focus on just two of them because they probably made the biggest impact on

human history. Cool. All right. So we've got Plasmodium Vyvax and Plasmodium Phalsipram, which I'm just going to call Vyvax and Phalsyperum from here on. That's good. Vyvax is the less severe and more ancient one, falciprim is more deadly and more recent. Interesting. I didn't know that that falsipram was more recent. Vibax probably showed up in hunter-gatherer groups many thousands of years ago and caused sporadic but deadly outbreaks. And we know this because of something called the Duffy Antigen, which prevents Vivax from entering the blood, like the red blood cell.

What? So if you are a person with the Duffy blood type, then you are protected from Vivax malaria. That is really cool. And because Vivax was probably so severe, in those early years, and this mutation was so beneficial, the Duffy antigen spread like wildfire throughout much of Africa. And by around 5,000 years ago, nearly every person born on the African continent had the Duffy blood type. And so is that why you basically don't see VIVACs in Africa? Exactly. That is so awesome. Yeah. Cool. And today, the proportion of black individuals from

Africa with this blood type is between 90 and 100%. Wow. So it's persisted. Oh, absolutely. Man, that is very advantageous. And despite the Duffy mutation, Africa would not remain malaria-free for long. Another malaria parasite was about to take Vyvax's place. Enter Phalsipram. Phalsipram probably made its appearance when people began to farm in or near rainforest in central Africa. So there a new malaria parasite emerged, taking advantage of settled groups, so more stable where it could have. actually persist in a community, whereas VyVax was able to survive prior to, like, large,

settled groups because of the dormancy. Ah, that makes sense. Super cool. Yeah, and then there was also a more efficient mosquito for falciperum disease transmission. Phalsyperum, when it first popped up, would have been really devastating. So devastating, in fact, that when yet another mutation, this one protecting against falciperum malaria appeared, it rapidly spread to the African constant. This one you may have heard of, sickle cell.

I'm not going to delve too deeply into the biology or the genetics of this one, but basically people with one copy of the sickle cell allele have blood cells. Actually, people with one or two copies of the sickle cell allele have blood cells that have a shape that prevents the felsiper and parasite from entering them. They're sickle-shaped. Yes. Yeah. There are other mutations with a pretty high prevalence that are linked to malaria,

such as G6PD deficiency, thalassemia, and about one in 14 people on Earth has one of these mutations. Wow. Yeah. Anyway, with these two very protective mutations, malaria should have been history, right? Right? Yeah, not so much. Too sneaky. By the time that pretty much everyone in Africa was protected against Vyvax malaria, it had escaped to Europe and Asia,

and falciproon would continue and continues to wreak havoc on the African continent. Malaria doesn't leave any traces on skeletons, but we can track its history through human genetics like I just talked about through examining mummies and through ancient writings. What can we see in mummies? Yeah, I was just going to say this is so cool. Malaria antigens were found in 5,000-year-old Egyptian and Nubian mummies. No dang way. They tested their tissues. God, mummies. Science.

Science. And there are mentions of a cyclic fever, probably malaria, in ancient Chinese, Greek, Roman, Sumerian writings. Wow. In Rome, Vivax probably contributed to the fall of the Roman Empire. Yada, yada, yada. Like, every stinking week, I say something about the fall of the Roman Empire. Yeah, it's not, it's not this podcast will kill you if we don't mention ancient Rome. Ebola might be another story, but that's okay.

Maybe. I'll find a way. Yeah, so, but I got to tell you, I'm not going to go talk about the Roman Empire, but I do want to tell you about some of these Roman cures for malaria because what were they thinking? All right. So you're a citizen of ancient Rome. I have my toga on and I'm holding, someone is holding grapes that I'm eating. Exactly. Oh my gosh.

I'm there. I'm your doctor. You probably shouldn't trust me. I don't. You have no choice. I do. Oh wow, you have recurrent fever and chills. Well, that sounds like malaria.

I could prescribe you some honeysuckle dissolved in wine. Oh, it sounds delicious. Right. It sounds pretty nice. Or I could instruct you to consume the liver of a seven-year-old mouse. How are you even going to find a seven-year-old mouse, for God's sake? I assume it's killed and then preserved for seven years. Oh, that's even worse than just a really old creaky mouse running around.

Well, I could also tell you about my famous meal combo of bedbugs, eggs, and wine. Okay, what? Not bedbug eggs, but bedbugs and eggs. Like a chicken egg? Yeah. Why? I don't have those answers. How do you prepare the eggs?

Again, I assume over easy. Oh, my God, this sounds a try. I want to leave Rome. Well, whichever one of those you choose. Honeysuckle. Duh. Sorry, but I'm going to prescribe you whatever I think is best. And I'm also going to prescribe you a piece of papyrus that you're going to wear around your neck with the powerful word abracadabra on it.

Yes. No, abracadabra, that is where abracadabra comes from. Stop it right now. Malaria. It was to prevent malaria in ancient Romans. Stop it right now. It took everything I had to hold this. This factoid from you?

So I wanted maximum impact. Abricadabra means go away malaria? Mm-hmm. Oh my God. Well, I don't know if it necessarily means... We're going to say it means... I looked at the etymology and it seems like nonsense. Go away malaria.

Oh, my God. That is the best news I've ever heard. Yep. Okay, so we got abracadabra. We got some mouse livers. We got some bedbugs. We're done with ancient Rome. There's nothing more.

I need to leave this place. I'm going to talk a little bit about more modern Rome, I guess, like not modern day. But it's important because Rome in like the 1500s, I think is probably where malaria actually got its name. Oh. So malaria, Mao, meaning bad and aria or area, whatever, meaning air. Bad air. So remember the theory of miasmatism? I do. The idea that disease is caused by foul smelling air and certain weather patterns. Yeah. That is what. was at play here when malaria was coined. Right. It's just the bad air that you're breathing in. Right. People notice that it occurred more frequently in the summer and in low-lying marshy areas, which also happened to be when and where mosquitoes are most abundant. Great mosquito habitat,

those marshes. But the root of transmission wouldn't be figured out for a while. Yeah. And we'll get there. But first, let's head to the new world. Let's go on the boat. Before Columbus and the European invasion of North and South America, the Western Hemisphere was free of malaria. What? Mm-hmm. I don't think I even knew that. That's embarrassing. That's why you're here. That's why I'm here too.

Yeah. So both Vyvax and Falciprim were brought over by Europeans, particularly during the slave trade. In fact, some historians suggest that the slave trade was so massive because two things. One, wide-scale colonization of Africa by European. hadn't been successful because falcifuram, the more deadly malaria, would kill so many of the European invaders, while Africans had been exposed to the disease as kids and were more protected. Yeah. So there was more emphasis on invasion and colonization of North and South America instead, where all of

the indigenous people were killed by the invading diseases as well. Right, like smallpox and then malaria. You know, I guess I actually did know that about the slave trade in malaria, so I'm not that stupid. Okay, but there's a second reason that the slave trade might have been so massive because of malaria. Why? So, as we've heard in other episodes, Europeans brought with them a bunch of diseases that wiped out up to 90% of the Native American population in the first few decades of colonization. See episode three. Mm-hmm.

Which the Europeans saw as wiping out their potential workforce slash slaves. Wow. So they turned to Africa and ramped up the slave trade to compensate. Cool. Mm-hmm. Although malaria was new to the Western Hemisphere, there was a secret there, hidden in the forested hills of the Andes. The Sincona tree. The bark of this tree contains a chemical called quinine, which, when ingested, reduces the symptoms of malaria and basically cures you.

The Quechua people of Peru, Bolivia, Venezuela, and Ecuador had been using bark from the Sincone tree for ages prior to the European invasion, But when malaria started popping up, they saw that it was also an effective treatment for that illness. Some Jesuits from Spain noticed this Quechuan practice of treating malaria with this bark and co-opted it, bringing the powdered bark back to Spain, announcing it as a miracle cure, which it really was. Yeah. And calling it Jesuit's bark, claiming that they had discovered it and its practice. Pretty typical. Uh-huh.

It's like, come on, guys, really. Europe was still very much malarious, I think that's a word, at this time, which is like the mid-1600s, and when the news spread about this miraculous fever tree, the race was on to find these trees, get their bark, and most importantly, control their production. Yeah. There were many missions failed and successful to harvest saplings, collect seeds, and bring them back to Europe to be planted. It became a huge commercial venture with a lot of political turmoil. The Sincon tree was almost harvests. to extinction.

Wow. Exporting these trees out of Peru and selling the seeds was quickly outlawed, but that didn't stop it from happening. And the Dutch maintained some pretty huge Sincone plantations in Indonesia while the British had some in India. Wow. Of course, only wealthy people could afford to purchase the treatment, which kind of set the precedent for malaria being a disease of poverty.

Yeah. The other thing that Sincone bark did was to enable the colonization of parts of the world that had previously resisted because of the amount of malaria there. Now Europeans could travel to and invade these places, such as India, such as parts of Africa, as long as they took with them a suitcase full of seeing cone bark. Wow. I mean, so I'm kind of speculating over here, but I don't think it's necessarily a coincidence that the whole Manifest Destiny, British imperialism movement really hit its stride as soon,

or soon after access to a malaria treatment was possible. fairly easy. Oh, definitely not. I mean, British officers in India invented tonic water as a malaria preventative because quinine on its own was too bitter. So those of you who are drinking along with us or have ever had tonic water, you have ingested quinine. Aaron is guzzling the rest of her. Yep. You heard it. That was the last last sip. Holding my glass waiting for the moment. which I could. So quinine is a really bitter, bitter tasting. Apparently it has some really nasty side effects. And so in order to take it and not vomit immediately afterwards, got to mix it with gin. Gin, sugar, tonic water contains a lot of sugar. Yeah. And so, yeah,

so it's in all tonic water. Even though by the late 1600s there was an available treatment for malaria, people didn't discover the cause or transmission root of malaria until the late 1800s. In 1880, a French surgeon named, I don't know how to say them. Okay, I'm going to give you, I'm going to prompt you. Alphonse. Alphonse. Leveron. Leveron.

Thank you. It was beautiful. Derien. What? That means you're welcome. Clearly, I know zero French. Okay, so this guy, Leveron, Leveron, glanced into a microscope at a smearance.

of blood from a malaria patient and saw something wriggling in the blood cells. He knew that this was not a bacterium. It was something new, something he had never seen before. Riggling. And he figured that it was the causative agent of malaria, and he presented his findings. Cool. Yeah, which were met with scorn by the leading bacteriologists of the day. Typical. Who had already decided that malaria was caused by an airborne bacterium, thus supporting the whole myasmatism. theory. I just love it. Anyone who works long hours knows the routine.

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Train to 32 32 32 32. They completely shut him down, but Leveron didn't back down. Instead, he doubled down, also claiming that malaria was transmitted by mosquitoes, even if he didn't have any evidence to back that up. He just was like, I've decided. Yeah, so the role of the mosquito. in filariasis had recently been discovered and so he was like just jumping on that train. Well, I mean, that makes sense.

Oh yeah. I mean, he clearly had a good instinct. A wriggling thing and you're like, that doesn't look so different from what causes this. It's got to be a mosquito. Yeah. Seems like a smart guy to me. I think he eventually did get a Nobel Prize. Cool. But all of his findings at the time more or less fell on deaf ears.

Eventually, he would be proven right about both, but that would take a couple of decades. Wow. In the meantime, the moment, the time. The French had decided to build a canal through the little landmass connecting North and South America. Oh. You know, Panama. Such nostalgia. We both did our fieldwork in Panama.

Yes. The entirety. We spent months. Many months, especially in your case. Yeah, I spent years. Literally years. Literally. Panama had been the bane of Europe's existence for a while since it inconveniently blocked easy transport from the Atlantic to the Pacific oceans.

How rude of it. I cannot believe it. At its narrowest, Panama is about 50 miles or 80 kilometers across. It's actually a little bit less than that. So small. It's very small. And the Spanish had previously built a trail. Actually, the Spanish had their slaves built a trail, known as the Camino de Cruzes,

to link these two oceans. But the forests were full of malaria and yellow fever, and in the rainy season, huge parts of this trail would be washed away. And I should know, because I used to walk along. what remains of this trail every week during my fieldwork. Didn't you find a lot of really cool old bottles and junk on that trail? Yeah. So cool.

It was my favorite thing in the world. Anyway, fresh off the success of the Suez Canal, the French engineer Ferdinand de Lesseps. Sounds right. Was hired to cut into Panama. Construction began, but progress wasn't really made. Workers were dying by the thousands from malaria and yellow fever. In eight years, over 22,000 workers.

died in the construction. Wow. Eight years. Twenty-two thousand lives lost. That's half the students at this university. It was a complete disaster. That is awful. Yeah. So the French after this, they were like, okay, this isn't working. Yeah. So the whole project was abandoned for a number of years. Oh my God. A few years after the canal was canceled, a couple of researchers finally showed conclusively that malaria was transmitted through the bite of a mosquito. And this finding, though, would come too late for the thousands of workers who die during the first canal efforts. Yeah. But not for the second, a successful attempt to build a canal.

When the U.S. took over canal construction, they hired a guy named William Crawford Gorgas to act as medical specialist. Gorgas! Gorgas. One of the first things that he did was to start a full-on war against the mosquito. He put in screens, drained swamps, oiled puddles, and fumigated buildings in the area known as the canal zone. As a result, malaria was more or less driven from that part of Panama, but not outside it. Only in those areas that he directly targeted, which of course were the areas where

the Americans were living. Just a bunch of white people. And also since living quarters were segregated by race, only the buildings for white people received screens or were treated with pesticides. Oh my God. Yep. It was really typical and crappy of them, horrible of them. Anyway, but it was enough to get the canal built. It's funny because Gorgas has hailed by so many as the man who conquered the mosquito, but he was very specific. Right. The only reason that it persisted, that malaria control persisted in the canal zone

is because Americans stayed in the canal zone. Right. Until like the 1970s. So they kept up with that type of control. Exactly. Right. Once it became widely known that the mosquito was responsible for malaria, many countries took the same approach as Gorgas.

Control the mosquito and you control malaria. This is when we see DDT and other pesticides make a big appearance. DDT. Spraying campaigns were going so well in the first half of the 20th century that people started to talk about eradication. Yeah. Let us spray. Let us spray.

Was their motto. And let us spray. Let us spray. I love that. Malaria was completely eliminated from areas that had been so badly afflicted. before until a new case popped up here and there, which was confusing since there shouldn't be any mosquitoes left. Yeah. That's right. Pesticide resistant mosquitoes. Oh, man. Bad news. Bad, bad, bad, bad news. Malaria-infected mosquitoes quickly reestablished themselves and caused disease,

which was so much worse because people didn't have the past exposure to gain a bit of immunity to protect themselves. Yeah. The death tolls were super high, and the spraying campaign stopped, both because of resistance evolution of resistance, but both because of the evolution of resistance, but also because of the devastating effects of these pesticides on wildlife. Yeah, DDT is... With the Rachel Carson Silent Spring. Right. It's really gnarly.

Okay. Public health professionals were like, well, I guess we'll just have to try another approach. This time, they targeted the parasite rather than the mosquito with drugs. Again, huge numbers of people were mobilized to administer newly-divided. developed powerful drugs to treat and prevent malaria. Again, it worked, but again, only for a while before the first drug-resistant cases popped up. Efforts were soon abandoned, and by the 1970s and 80s, a lot of the funding for malaria had dried up. There was a huge upsurge in cases around this time,

but no real focused efforts to relieve the malaria burden in those areas most impacted, because a lot of the early 20th century campaigns focused on wealthier countries. So the southern U.S., I mean, malaria was endemic in a lot of the United States, the southeast United States. It went up the east coast. It was in Europe. So once those areas, which were first targeted for eradication, once those were cleared, it was kind of like, well, I mean, you know.

The white people are safe, so, hey, we've done our job. Mm-hmm. Yeah. My story kind of ends around then. with the sad facts that the incidence of malaria really increased following this decline in funding and sort of the shutdown of all of these spraying and drug campaigns. So tell me what you got for today. Yeah, that's where I should step in then.

Got it. So first of all, as of 2016, nearly half of the world's population lives at risk of malaria. Half. Half. So that's like three and a half billion people or so. We're putting that on the table right away. It's literally over three billion people live in areas that have malaria transmission in 91 different countries. Wow. It's a lot of countries.

That's a lot of people at risk for malaria. A lot of people probably getting malaria. Right. And the money that you're talking about that dried up back in the 60, 70s, 80s didn't really start flowing back towards malaria. research and prevention until 2000. Whoa. Yeah, I know. I thought that had to be wrong.

But the other thing that's really important to keep in mind when we're talking about malaria is that when you look up these numbers of cases and numbers of deaths, they're basically guesses. They're educated guesses. They're guesses that are based on some surveillance and a lot of statistical and mathematical modeling, but they're still just guesses. And depending on who you talk to or whose paper you read, they're either really great guesses or there may be not that great of guesses. And this is especially important because the guesswork in this case extends not just to guessing how many cases and deaths there are,

but how effective the interventions have been in reducing those cases and deaths. So it would have to be like a massive reduction to detect any sort of. Kind of, yeah. And just to really understand like how big of an impact is this intercourse. intervention having versus that intervention. Right. So any sort of evaluation is really difficult. Yeah.

So in 2006, WHO estimated that there were 216 million cases of malaria worldwide and 455,000 deaths. That was last year. Let me just say that again. Yeah, I need to repeat that. It was repeating. Last year, there were 216 million cases of malaria. area and 445,000 deaths estimated. 285,000 of those deaths, this is larger than the population of the town I grew up in, were children under the age of five.

For a disease that has a cure and prevention or preventative drugs. Yeah. That is horrifying. Yeah. almost 90% of these cases and 91% of the deaths happen in Africa. So one study that I read, and so this is where we'll start to talk about the interventions and the fact that believe it or not, these numbers are better than they were. Wow, that's really hard to believe.

I know. So this one paper that I read estimated that in 2000, in Africa alone, there were 321 million cases of plasmodium falcipro. The bad one. The bad one. And by 2015, that number had dropped to 187 million. So that's a 40% reduction. And it took 15 years for that 40% decline. And since this is so much guesswork, I mean, do we think that that's a real decline?

Well, it seems like it's a real decline. So this study specifically could detect that about 68% of this reduction could likely be explained by the use of insecticide treated nets. So bed nets treated with long-acting insecticide, long-lasting insecticide, are one of the main intervention methods that people use to control malaria, to prevent malaria. They're quite effective. They're cheap to make, but they haven't always been available cheaply to people. Right. I saw somewhere that said $5 a bed net in an area where the average daily income was less than $1. Yeah. It wasn't until very recently in the 2000s that the WHO made it one of their main goals to get these insecticide treated nets to every household, especially in Africa. And so I think, I don't know, I hope that that number on $5 per net came from prior to that time.

Yes, it did. The other things that are commonly used to control malaria besides bed nets is something called indoor residual spraying, which essentially means instead of long. like the massive DDT campaigns of the past where we just sprayed DDT throughout the whole air and all over everything, this is just spraying the inside walls of your house. Because what mosquitoes do, this is fun. She's very excited. Yeah. After a mosquito takes a blood meal, it's all fat and full of blood and it's like, oh, I'm tired.

It's hard for it to fly. So she goes, I'm sleepy. It's so ridiculous. Anyways. So she flies off and she takes a rest and she usually lands on a wall to take that rest, a vertical surface. Oh. Yeah. Sorry. I jumped the gun. I think I know you're going with this. Yeah. So treat the walls, kill the mosquitoes. So there are several problems with this. One is that you kind of have to spray at least 80% of the houses for this to be effective, which is a hell of a lot of work. Yeah, that's going to be really hard. Right. The second is it only lasts for about three to six months.

months. So you have to do this every three to six months. And lastly, do you want to take a guess? Resistance? Resistance. Yeah. So insecticide resistance is already happening. It's been happening, right? In many parts of Africa and in many parts of the rest of the world where malaria is still endemic, you have resistance to all four classes of insecticide that are used. Uh-oh. Yeah. I mean, that's four. That doesn't really quite. Cover it. There's like four different main entire classes of insecticide that act in totally different ways on totally different systems. And some species of mosquito have shown resistance to all four of those classes.

We don't have a lot of options left. Because of this, physiological resistance, potential behavioral resistance, indoor residual spraying, while it can be effective, might not be that effective. The other scary thing that you talked about already is this drug resistance, because the other main way of malaria control is combination therapy, at least two different types of drug. The problem is that this parasite is already resistant to the main drug that's used, and in a lot of countries, in a lot of places, it's developing resistance to some of the secondary drugs that are used as well. Yeah, so that's pretty scary. Another thing, I don't know, is climate

change. Oh, yeah. This is my sweet spot. It is. It's like your favorite thing. Yeah, well, I mean, to talk about intellectually. Well, no? I would say that that's more in my wheelhouse in terms of my dissertation. Definitely. There's a lot of conflicting opinions out there on what the effects of climate change are going to be on vector-borne diseases. Yes. And at this point, what we know for sure is that things are likely going to change.

That seems very reasonable. We don't necessarily know the exact direction of these changes. we don't necessarily know if things are going to get better in some areas and worse in other areas or if they're just going to get worse or better overall. But what seems pretty clear is that... In talking about infectious diseases. Right. In talking specifically about vector-borne diseases.

Right. It's going to be very location-specific. Exactly. So some studies have shown with math modeling and things like that, that it's very possible that the distribution of malaria could change going forward because of climate. climate change. So we might see these mosquitoes and in some cases we already are seeing these mosquitoes move up to higher altitudes where they were never previously able to live because it would get too cold. We could also see a shift from coastal regions to more inland regions.

And so all of this could very dramatically affect the malaria burden that we actually see in humans. So then the question becomes, what do we do moving forward? It's a really tricky question. Yeah, it's, there's not a clean answer for this. So I just want to talk about something that I'm into. Okay. Because I can. Let's do it. It's our podcast.

Again, why we're here. Right. So one thing that I am super interested in is the possibility of transgenic mosquitoes. Oh, yeah. I know people are going to hate me for, well, maybe we'll get our first hate mail for this. Some GMs. I would love it. If we got some GMSs.

You would love a hate meal? Yeah, GMMs. If we got some, yeah, I mean, kind of. I'd be thrilling. I don't want hate mail. Okay, don't send us hate mail. So there's a lot of really cool research that's being done on how to make these mosquitoes less permissive to malaria infection. What does that mean?

So it basically means that instead of focusing on stopping these mosquitoes from biting you, or curing everyone with the parasite, or removing mosquitoes from the ecosystem, this looks at blocking the cycle of reproduction of the malaria. parasite within the mosquito. Okay. So there's a few different groups and a few different ways that people are looking to do this. Actually, what I think is cool is there were two different groups that published two different papers in the same issue of science in September of this year that we're looking at two different strategies to do this. Oh, man, I bet that they were racing to both get it ready by the time.

I'm sure that science was like, okay, guys, we're going to do this on purpose. I just put them both in one. I just hope that these two groups are more less like Salk and Sabin and more like Aaron and Aaron. Get it? Like they work together. Collaborative, cool. Hilarious. Anyways.

So one of these groups was looking at using a genetically modified bacteria that's found in the gut of mosquitoes that can help to fight off the plasmodium infection. Whoa. Yeah. So it's this bacteria that's. It's normally present in the gut of all mosquitoes, but they basically genetically modified it to produce more compounds that would help the mosquito fight off this infection. Because don't forget that this plasmodium, this malaria parasite, is bursting through the gut wall of these mosquitoes and traveling through their body to get to the salivary glands. So the mosquitoes generally have some sort of immune response to this. It's not like a totally benign infection necessarily in the mosquito.

So you can kind of jump on that train with this bacterium to try to stop the infection overall. Exactly. Whoa. And the other study was looking at genetically modifying the mosquitoes themselves to basically produce more immune compounds to fight off the infection itself. That's cool. It's very cool. And that study was really interesting because they actually found that genetically modified males were more likely to mate with unmodified female.

So basically they were good at sending this gene forward, which is one of the big challenges of genetically modifying mosquitoes, is how do we get this gene into the population of mosquitoes that already exists? I love this stuff. So is that the state of malaria today? That's the state of malaria today. That is a, it's depressing. It's depressing.

It's a little bit uplifting because it seems like there's work being done, but it's really disheartening that there are still so many over 200 million people infected every year. Every year. Wow. Yeah. And it was actually a little higher in 2016 than it was in 2015. We are definitely not seeing the declines that we have seen in other diseases that we've talked about. So, yeah.

All right. Well, sources. Sources. All right. Okay. I read a few books. One is called The Fever by Sonia. Shaw, and this is a really great overview. It's really written well. It's interesting. I really liked it.

Take a look. She's a great science writer. The other is called The Making of a Tropical Disease by Randall Packard, and that's a more, it's a less accessible take on the history of malaria, and it focuses largely on the role that agricultural practices have played in the transmission of malaria, and I wish that I had more time to talk about it because it was really interesting to see how small-scale farming versus large-scale farming, et cetera. Anyway, take a look if you're interested. And the final one is called The Fever Trail by Mark Honingsbaum. And it was interesting.

I don't necessarily highly recommend it just because the readability was a little bit less. But it was very cool. It mostly focuses on quinine and the discovery of the Sincona tree. I've got several papers I want to cite today. I always cite the digital. WHO, but at least three other papers today. So one was by Bot at all in Nature, published in 2015, and that was the paper on the effect of malaria control on P. Falcipram in Africa between

2015. And then the other two were the two papers about genetically modified anophiles and genetically modified bacteria. Those were both published in the September, 2017 issue of science. So you can find those. The first one is by Wang and the second one is by Pike. Hot off the presses.

Hot off the press, September 2017. There was a bunch of others. So if you're interested in any specific aspects of malaria, shoot us a message or something. And also, just as a reminder, we do have a Goodreads list, which has all of these books. And we're working on getting a Google Docs up for the different articles that Aaron mentioned. So you can take a look at those if you're interested in reading further.

Yeah. I think that that about wraps up our episode today. It does. Thanks again to Umat for providing his first-hand account of malaria. Super interesting. And also thank you again to Bloodmobile for providing the music in this episode. And for all of you bird people out there, one of the songs features a bird native to the Andes. So see if you can pick it out.

Rate review and subscribe. Please. Please. Follow us on social media. And thanks for listening. Thanks so much. Now wash your hands. You filthy animals.

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