Ep 81 Chagas disease: The Reverse Triple Discovery

Shaga's disease when I was about five years old. My auntie was diagnosed with Shagas in New York City actually, and she was from Colombia where around the time that she was twenty nine, she started to get really seriously sick and the doctors in Colombia were able to do some exploratory surgery, which is how they found out that her large intestine was under some kind of attack. They actually did not diagnose her with Shaga's disease. It was

in New York City that that happened. And my auntie was very lucky that she was diagnosed and she was able to to receive some interventionist kind of treatment at that point. But you know, she had chronic Shagas disease for the next almost three decades of her life, and so she well, I was growing up, she was in and out of hospitals over the years, and sometimes she was in the hospital for one night or two nights, and some years she was in the hospital for a

month or two. The parasite ended up not only affecting her large intestine but also her esophagures. She had multiple surgeries during these years, and I grew up thinking that Shaga's disease was a very rare or unusual illness. I thought my Auntie had just been extremely unlucky. And it was not until twenty ten when she became very very ill and actually died from this disease. That was the point at which I started asking questions about Shaga's disease.

I think because I had grown up without knowing anyone else who had this disease except my Auntie, I thought it was rare, and I was really surprised to find out that there were that there are an estimated three hundred thousand people in the United States who have Shaga's disease, and they're like my Auntie's. They're immigrants from South America, Central America, and Mexico. And that number was very shocking to me, and it made me wonder who these families were.

And that's how I ended up starting my book actually was that I wanted to meet other LATINX families in the United States to find out what their experiences with Shaga's disease were like, and what obstacles they were facing, and just how they were navigating the medical system in this country, given that, as far as I knew, was a very neglected disease, and something that I discovered while working on the book that I did not know know about when I was a child was the issue of

congenital Shaga's disease. I met an incredible woman in the DC, Maryland area named Janet, who is from South America and her second son was born here in the United States with congenital shagus She herself knew about the disease. Similar to me, she thought that it was an affliction of Actually, in her case, she thought it was the elderly because she knew her father had Shaga's disease. She knew her

older sister had Shaga's disease. She comes from a part of South America where the disease is pretty common, but she, even though it's common, she did not know about congenital Shagas disease and her son was born already having cardiac complications due to the disease. I'm happy to share that the baby is now gosh now five or six years old, and is very much is doing well. But he was

a very unusual case. He ended up being only the second documented case of congenital Shagas disease in the United States, and he was unusual just in that he showed symptoms. Her situation, though, also really touched me because she herself

did not have health insurance. She was not working, she had a toddler and a new baby, and she was home and her husband worked in construction, and she did qualify for the Affordable Care Act or for Obamacare, but she had not signed up for it, and it's an additional expense that the family would have to bear, and so she really struggled to actually find a medical provider

who could diagnose her, who could work with her. It was a series of obstacles that I kept hearing over the years that I worked on this book, while I was talking to both families and medical providers. Is this constellation of obstacles not having health insurance, not being fluent in English, sometimes being fluent in English, but really struggling to advocate for yourself with a medical provider who doesn't know about the disease and doesn't understand or isn't being proactive.

And also something else which came up often, which is that you know, if patients aren't experiencing symptoms, they have so many other things that feel more urgent and are more urgent in some ways in their lives. Like in Janet's case, she was, you know, very concerned about her child's welfare before her own. She was concerned obviously about her family's financial life. She herself has a legal residency, but was trying to learn English to work towards citizenship.

Other families that I interviewed, you know what felt more urgent in their lives were the immigration status of different family members and job security always comes up, and so it's easy it becomes easy to actually ignore or Shaga's disease in a way because they're not having symptoms and it's not the most pressing concern in their lives. Although I knew about this disease from a very young age, there was a kind of stigma in my family around it. My auntie never wanted anyone to know about this.

married an incredible man. She had such a wonderful life in so many ways, and she didn't want to have this disease and felt like it tarnished I think when I was growing up, I thought it was very normal that we did not talk about Shaga's disease. We did not tell anyone that my Auntie hadd We did not mention it. It definitely felt like something that we were supposed to have shame around. And now I look back on that was so much sadness because it was just

a lack of information for my own family. It was a lack of information of course, in the healthcare community in the United States. The one sadness that I have is that I do wish my auntie had lived so that I could tell her a lot of what I learned about the disease, you know, even the difficult parts of this, you know, even the learning about congenital shaugus,

Like I wish I could have told her that. I wish that I could have told her more about just all these you know, species of this insect, of the triotomine insect. I wish I could have told her about that. Even though she hated insects, she would not have wanted to probably hear that much detail. But I do wish, and I do have sadness that I could have told her, because I think that ultimately she died knowing very little

about her disease. And so for me, part of working on the on the book was also a desire that people who have shagas and their families have a chance to know what they're really facing, you know, and and so that you know, no one else should have to die without knowing about their own disease and what's happening to their bodies.

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bite or a scratch. Okay, multiple people have written in It turns out, unsurprisingly when you really think about it, it is largely flea feces that are to blame. So infected flea feces or in some cases, just infected cat's blood itself, can contaminate a cat's claws during grooming, which then can introduce the bacteria via a scratch into our skin or a bite wound. Fe flee flea feces can contaminate a bite wound, et cetera.

It has a little like looks kind of like a comma with like wavy flagella. Okay, okay, picture it's cute. So Tea cruise I has a shall we say, relatively complex life cycle. So we're gonna go through the life cycle and then from there we can understand the different ways that we as humans can get infected. So we'll start the life cycle in the bug, the insect vector that transmits it. So Tea cruise ie gets picked up during blood feeding by bugs like you mentioned aaron called

kissing bugs aka triatomines. They have a lot of different names in different countries. Kissing bugs are a type of what's called true bug in the order amypdura. Okay, already, I'm on tangents. These are blood feeding insects. I think a lot of people might not know what they look like, so let me paint you a visual. They're pretty large bugs. The adults are like between three and four centimeters so a good inch inch and a half long, and they look like they have like a flat oval body with

a pointy head and a long curved preboscis. That's the straw that they use to drink blood. So these are big honkin bugs. They're big, right, Like, way bigger than ticks, way bigger than mosquitoes, way bigger than most things that bite you.

up a whole bunch of parasites. These parasites travel through the bugs guts, they differentiate, they replicate, and then when that bug gets hungry again and goes to take another blood meal, that bug will poop, and in that poop or frasts are a whole bunch of parasites, not unlike the fleas in Bartonella.

our cells. They actually can penetrate a pretty wide variety of cells, and what cells or what tissue type they infect can then lead to different symptoms of disease. They replicate, they differentiate again inside our cells, they replicate a whole bunch, and then they burst out from our cells to travel through our bloodstream and either infect another cell and start a new replication cycle to just keep going, or in the bloodstream they can be picked up by another kissing bug,

thus completing their life cycle. So that's just like the life cycle of tea cruise eye.

has like six different clades within this species. And these different clades vary in terms of virulence, so how sick they make you and disease manifestations, what tissues there may be more likely to infect, or how likely they are to cause more chronic disease. And these different clades can vary in geography, they can vary by vector. There's a lot of variation in these different clades of T. Cruizy.

Then there's the vector. And I hinted at this already, so I said that it's a triatomine a kissing bug, but aarin is it just one bug?

so in walls, in roofs, inside of our homes. So historically that's been the one considered kind of the biggest deal. But there's a lot of other species in a whole bunch of different genera of triatomine that are capable of and potentially important of Shaugus disease. Spoiler, that was like my whole dissertation. So like I could go on and on, but I think I can pause there. Okay. Each of these species has differences in terms of their ecology, so

like where they like to live. Do they live in palm trees or do they live under rocks, et cetera. They have differences in terms of who they like to feed on, and like you asked Aaron, how often they feed, they have differences in how long they feed for, how soon after feeding they take a poop, and where they take a poop after feeding. It's really really complicated.

really complicated. So we know that in general, this is a group of insects and therefore parasite and disease that was typically considered endemic to the New World, so North Central and South America and mostly just the southern part of North America because it's really restricted to more tropical type latitudes. But as we'll see when we talk about the clinical picture of disease, which I promise I'm about to get to, because of the way that Shaugus disease

manifests clinically, it is a global disease today. It is not limited to South America or even just the Americas. So let's talk symptoms in humans. Shagas disease has two forms, the acute disease like you get sick shortly after getting infected, and then a chronic disease. This parasite can lay dormant in our bodies for decades ten twenty thirty years and then pop up and cause disease very long down the road. So we'll go through those one by one. In the

acute phase. Honestly, shacus is mostly asymptomatic, and by mostly I mean ninety ninety five percent of the time completely asymptomatic. So you get bit, you scratch this parasite into your bloodstream, and you don't know about it at all. If people do have symptoms, so that five to ten percent of people that do have symptoms, they're often quite mild and consist of something like maybe some fever, maybe inflammation wherever

the parasites entered. And because it's common for the parasites to enter via something like your eye, there's a classic sign that's called Romagna's sign, which is when one eye whichever i the parasites win in from, gets really swelling swelling of your eye and eyelid. But it could be anywhere. So let's say it happened on your arm, then maybe your arm swells up. Occasionally you might also get some

hepatosplenomegaly one of our favorite, oh my words. Yeah, so that's swelling of your liver and spleen from the parasite and inflammation and immune response associated with it, or swelling of any various lymph nodes. Potentially it can cause things like anemia if it gets more severe, and in very rare instances, like I think, usually only one to five percent of the time, although one paper I read said

five to ten percent. It can be a little bit more severe, and the specific symptoms depend on which organ is infected severely. So if it's the heart, we can see things like myocarditis or pericarditis, inflammation of the heart muscle or lining very rarely. If it infects the brain, you can get me ninjo encephalitis and these kind of severe manifestations can be fatal, but that's very rare.

a whole bunch of different tissue types. What makes them either decide or just happen to end up somewhere probably depends on how much parasite you have, Like how far they make it before our immune system kicks in. Probably depends on how great of an immune response you have to It probably depends on what specific genotype you were infected with. There's probably a lot of variables that I don't know the full answer to.

result of this infection. Okay, okay, okay, okay. So for those unlucky, thirty to forty percent of people anywhere from ten to thirty years after the initial infection, which again most of the time is asymptomatic, so you never know that you had it. The two most common organs that end up getting infected are the heart and the gastintestinal tract, and the parasite ends up doing similar things but with

very different outcomes since it's heart versus GI tract. Okay, So in the heart often what happens is this parasite and this infection causes an enlargement of the heart. It causes what's called a dilated cardiomyopathy, an enlargement of the heart. This causes the heart to not be able to conduct

electrical impulses properly. That's your heart's like one job, right, it's to have electrical impulses that all go simultaneously so that your heart contracts in one beautiful thump thump with enough force to pump blood to the rest of your body when it gets dilated, and those electrical impulses can't transmit, the heart can't contract in sync or it can't contract with enough force or the right timing and synchronization to

be able to push your blood forward. So there's a lot of different ways that this can manifest, anything from things like heart block to heart fail two different a arrhythmias, just depending on what parts of the heart are the most affected and when. But overall, the most common cause of death in these individuals is sudden cardiac death because your heart is just all of a sudden not able to pump properly, and then you die from sudden cardiac death.

The other organ that's most commonly affected is the GI tract, and same as with the heart, shaugust disease tends to cause enlargement of either the esophagus or the colon, either or usually in the esophagus This leads to dismotility, and specifically, it leads to something called a kalaysia, which anyone in

med school will be like, oh yeah, shaugus disease. A kalasia basically means your esophageal sphincter, the one that lets your food into your stomach, doesn't it relax properly, and your esophagus gets expanded and then it looks like a like a bird's beak. So there's a really tight hole where it enters the stomach, and then the rest of it is really dilated. Does that make sense instead of being a nice little tube. And so this leads to like not being able to swallow properly, et cetera.

is problematic. But what's even more worrisome is it can lead This dilation can lead to twisting of your bowels, which is called volvulus, and that can lead to ischemia because that twisting can then cut off blood float to the organ. Okay, okay, yeah, So it's a problematic disease and it's a cause of really really chronic disease problems.

and that's still true for the pathophysiology. So especially in the chronic phase, we still don't know the exact details of this pathogenesis, so we don't know exactly what's going on, but we know a few things. So we know that in the acute phase, the organ damage when it happens is due to direct action of the parasite, So it's parasites causing damage to the tissue from bursting out of our cells that stimulates an inflammatory response, et cetera, et cetera.

That's the acute phase, so you think probably similar things are happening in the chronic phase. We know that you asked about who gets chronic disease versus who doesn't. The balance of who gets chronic disease versus just who has infection without ever having disease from it seems to depend a lot on individual balances between our chronic inflammatory response and the parasite infection itself. So like, how much is our immune system trying really hard to kill off this

parasite versus just tolerating this parasite and like coexisting with it. Right, But Okay, it gets really complicated because in some areas where transmission has been reduced significantly, so where control efforts have reduced incidents of disease, but of course people are still infected, right because it's infection. The development of things like cardiomyopathy have actually decreased. There's been a reduction in

the development of things like heart disease. So it's thought that maybe there's also some interaction between recurrent exposure to the parasite and increased inflammation.

before I hand it off to you Erin. Okay, okay, Because it's important to mention that while this is largely a vector born disease, vector born transmission is the primary root, it is certainly not the only root. Right, So, because this is essentially a blood borne pathogen, this is something that can also be transmitted via blood transfusion, or organ transplant, but of course that's quite rare, and in many places

blood is screened for Shougust disease. It can also be a congenital infection, so during pregnancy it can cross the placenta and infect a fetus, which can result from anything from spontaneous pregnancy loss to premature birth, to a number of different problems in the newborn, or in many cases asymptomatic infection. But then life lung infection of the baby.

things sometimes, so yeah, yeah, definitely. So like always, let's start at the beginning, which is easier said than done. Until fairly recently, like maybe within the last ten fifteen years or so, the origins of Tripanosoma cruisy seemed like fairly cut and dry, or at least like as cut and dry as evolutionary origins can be in terms of like, you know, stuff, it's always being rewritten. It's fine, that's

how science works. But there was a general consensus that the Tripanosoma cruisi clade originated on the Southern super continent made up of South America, Antarctica, and Australia, where they evolved in isolation in early terrestrial mammals, and then when that super continent broke up around forty million years ago,

the tea cruisy clade further diversified in South America. And so if this were the sequence of events that actually happened, we would expect to see a great deal of diversity within Tea cruisy in South America, as well as maybe some evidence of coevolution between mammalian host and parasite with some maybe species specific strains. However, however, however, there's actually fairly low diversity of the tea cruisy clade in South American mammals like lower than you would expect if it

had been there for forty million years. And in addition to this, members of the tea cruisy clade also have been found in African and Australian land mammals. So what's going on here? Yeah, Well, it seems most likely that tea crusy originated elsewhere, likely in Africa, where the other major human tripanisome is most prevalent. So which is T. BRUCEI brucy, which is the causative agent of African sleeping sickness. We should figure how to pronounce that before we do an episode on that, which we.

two other trypanosome species recently described that are related to Tea cruisey are found in bats from Mozambique.

one is mostly associated with a possums and arboreal triatomines. Right, So, once these tripanosome infected bats infected with Tea crusey or some you know, ancestor of Tea crusy made it to South America, they were fed on by blood feeding insects triatomines that also took meals from other mammals also living in trees or a high right, yeah, like opossums. Yeah, And so then those apossums were probably some of the first to get infected with T.

but it might also have evolved after. In any case, this mode of transmission where where you know, opossums might be able to transmit through their poop or through like the anal gland secretions. This might play a role currently in semi urban environments or places where the vectors aren't quite as present.

Central America and North America through primarily animal movement. Eggs and nymphs, for instance, have been found to be carried in bird feathers, which I think is interesting. And then later, of course, human movement would have helped to spread things

along too. All right, By the time that humans arrived in South America, which was at least fifteen thousand years ago, tripanisomacruzie was present in animals across the continent, although to what extent is not quite known, since not all habitats might be conducive for the insect vector and whatever susceptible mammal species. But here comes the next First we thought it was this, then we realized it was that moment.

It was originally thought that humans first became exposed to the parasite after the domestication of like guinea pigs around two thousand BCE, along with other animals that would have like attracted the bugs and thus the parasite to you know, human dwellings, or it was thought that human dwellings built later on and particularly after European invasion, would have provided

you know, excellent homes for the triatomine vectors. And that's I mean, those things are probably true in that they did increase contact with the bugs, but paleo parasitology came along to change the story. The Atta Kama Desert in southern Peru and northern Chile is you know, it's a desert,

so as you would expect, it's extremely arid. There's virtually no rainfall, and so when a body is buried, it rapidly dehydrates rather than decays or disintegrates, and that has left many, many mummified remains in the area, and genetic analysis of these mummies has shown not only the presence of Tea Cruzy, but there are actually enough samples to

get prevalence estimates. What yeah, So, one study from two thousand and three screened two hundred and eighty three mummies for Tea Crusy, with the mummies dating as old as nine thousand years and as young as the eighteen hundreds. Wow. Yeah. Overall, the prevalence of tea cruzy was forty point six percent. Yeah, yeah, yeah, and that well, this is actually fairly steady over time.

I mean, there are a few dips and a few surges, but like, and the sample sizes in some of these groups are low and whatever, but that was that's a pretty like shockingly high number. I think nearly fifty percent

of people. Yeah, And the oldest of these mummies infected was this nine thousand year old mummy, and that indicated that humans in South America were exposed to the parasite long before domestication of guinea pigs and construction of European style housing or whatever, and that they probably first became infected from the sylvatic cycle of the parasite so between like the wild animals and the bugs. And that was well established by the first human occupation of the area.

And it's not just in South America, but also in Central and North America that we have evidence of prehistoric infection. The oldest known case in North America, for instance, is a mummy in South Texas from around eleven hundred fifty years ago with a mega colon full of feces. Oh wow. And analysis of these copper lights, because we love our copper lights shows that this person, I think this is so fascinating, like you get to see what.

colon or cardiac lesions. So it seems clear that humans became infected with tea cruisy basically as soon as they arrived in an area where it was circulating in mammals. And since that time, the geographic distribution of the parasite, the dominant genotype, the transmission route, the vector species responsible.

All these things likely shifted as human settlement patterns changed, as housing construction changed and like the materials, and as cultural practices changed, as well, but what didn't change and what remains true today is that there continued to be

opportunities for infection. So the prevalence estimate that I mentioned in the mummies from the Atakama Desert is like pretty dang high at forty point six percent, and in the more recent mummies tested like in the last six hundred years or so, it was even higher at over fifty percent. So people had to know about this disease, right.

trace the history. When did the name first appear, how often was it used, did it increase in use, etc. In the case of shagas disease, we don't have historical descriptions of the disease, but we do have a long history and a long current list of names for the

insect vector. Oh yeah, we have vinshu uka, a Quechua word meaning bug that lets itself fall chin chay, and many other nicknames that mean things like barber or sucking, blood, blood stealer, kissing bug, bug that dislikes the cold, big piercing bug, and so on.

of Rejuvius, the great black bug of the Pampas. It is most disgusting to feel soft, wingless insects about an inch long crawling over one's body before sucking. They are quite thin, but afterwards become round and bloated with blood, and in this state they are easily crushed.

the crew got sick. He eventually recovered, but later in his life he complained of palpitations, extreme fatigue, trembling, flatulence, and vomiting, and he was diagnosed first with hypochondriasis are you which is yeah and like a nervous condition or whatever they called it back then, and then later with heart failure after experiencing anginal attacks accompanied by extreme exhaustion and digestive disturbances that forced him to abandon his work.

But it also might not have been Shaga's disease, since at least some of these health problems that he complained about he had before he ever went to South America, So I mean it's possible. Who knows. And other descriptions of the blood feeding nature of the comes from Augustin Lizaraga, a Peruvian farmer who discovered Machu Pichu in the early

nineteen hundreds before Hiram Bingham stole all the credit. I just really wanted to throw that in there, because I didn't know that it like Hiram Bingham had stolen all the credit from somebody else. But I should have guessed. And then there are some earlier descriptions of the bugs, and even some that might hint at the disease by conquistadors.

Although these descriptions I didn't even put in because they're pretty hand wavy, Like one of them is like or it could be hemorrhoids, and I'm like, okay, well this look like kind of different.

leaving him to become head of the family. When he was old enough for college, his mother urged him to become an engineer, but he didn't pass the entrance exams and became very depressed until one of his uncles, who was a physician, was like hey, you know, why don't you try for med school? And so that's what he did.

And in his time at med school he focused his work on malaria, and after graduating in nineteen o three, he received an invitation from the man who had become his friend and mentor, Oswaldo Cruz oh Yeah, to work at the Hygiene and Public Health Office monitoring malaria and shagus Like readily took him up on this since he needed a steady income in order to support his new family like he had just gotten married, just had a kid, and when Shaugus began working there, he was not only

starting his medical career at a unique time, but also at a unique place. So around this time, in the early nineteen hundreds, theory had been fully embraced, and many pathogens and parasites had been described and were continuing to be discovered. Tropical medicine as a field was really starting to grow as imperialist countries struggled to develop the countries that they had laid claim to, with many people dying

of tropical infectious diseases. And for all its imperialist and colonialist beginnings, tropical medicine did mean looking at the whole picture of public health, from the life cycle and habitat preferences of a vector, to the epidemiological characteristics of a disease, to the economic and productivity costs of these infectious diseases. It involved combining applied and basic research with an aim

of prevention and control, not just descriptive knowledge building. Right and Oswaldo Cruz and the institute he founded, which was later to bear his name, the Oswaldo Cruz Institute, encapsulated this and then some. This institute placed the highest importance on the combination of research, education and assistance. Like other tropical medicine organizations, it integrated applied in basic research to

solve problems. But unlike the others, Cruz wanted his institute to focus not just on the economic benefits of urban development for the colonialist countries or like the big companies, but also on the improvement of the lives of Brazilians of everyone by preventing infectious disease. And Carlos Shagas picked up this attitude from his mentor, and it greatly influenced

his career and the way that he viewed medicine. In the words of his son quote, for Shagas, science was valid only if it was directed toward the welfare of humanity. Those are pretty good words.

His clinical background as a physician and his research background on vector borne disease it perfectly qualified him for this type of work, and soon he was assigned to a new, bigger project, a cross country railroad to transport agricultural products, the Brazil Central Railroad linking Belo Horizonte to Rio de Janeiro.

It was under construction, but it kept getting delayed when workers fell ill during malaria outbreaks like big bad outbreaks in nineteen oh seven, Shagas was called in to stop the outbreaks using the method that was most commonly employed at the time, combat the vector combat disease. Essentially, he was tasked with setting up research stations at the towns along the railroad ahead of the construction to identify potential malaria hotspots and then get rid of the mosquitoes.

And then third is usually when the root of transmission is determined, whether that means like arthropod vector or fecal oral or whatever. But what rarely, if ever, happens is that sequence in reverse.

But it was like, here's an obvious parasite that looks like not so dissimilar to malaria, which I'm familiar with. Let's feed it on a monkey. The monkey kids say, sure, it does, because any mammal will like what.

twenty by the WHO as International Shaugust Disease Day. Oh so, on this date he found this parasite in a two year old girl named Bernice, the first described case of what would later be known as Shaugus disease, and Shaga disease was named in fact by Oswaldo Cruz. Of course it was is that just like really cute. I just think that's really nice.

its life cycle and its intermediate and definitive hosts. He described his attempts to culture the tripanosome. He described the course of infection, and so on and Over the next couple of years, he continued to work on the disease, looking for it in more people in autopsies and better characterizing the acute stage of the disease as well as looking at chronic infection and long term consequences.

best work in parasitology and tropical medicine in the world. Wow. But all this success and acclaim came with an ample supply of haters, as it usually does.

and tried to discredit him. It's disappointing, I know why, well why and so I was thinking about like he got in some ways so lucky, right, like you were saying, yeah, there is always like with new discoveries, there is always resistance, Like there does have to be the sort of like ping ponging of like, well, wait a second, we need to introduce some healthy skepticism into this. And so maybe their attacks were way more personal than they needed to be.

But I do think at the time, you know, part of their skepticism or or hesitance might have been reasonable, considering also the fact that Shagus didn't get it all right in his first go but I mean, whoever does. But you know, he first thought was the bite of the bug that transmitted the parasite. You know, sorry, reasonable, It's very reasonable. And then the French parasitologist Alexander Brimpt

soon realized it was through the feces of tritomines. And but the other big thing, the big mistake or false association that Shagus made, was that he incorrectly associated the disease with goiters, which were really prevalent all across Brazil, Goiter's being caused by an iodine deficiency, and so other researchers were finding people with goiters but without tripanisamiasis. Without it, couldn't find the tripanosomes. And so they were like, we're not, like,

you're seeing something that we're not seeing. And I feel like the reverse story where those detractors, those haters like have been right in other histories of disease, where they're like, you're not seeing what you're seeing, it must be something else. So anyway, it's just it's the way history is written now.

And so some of these haters might have simply been jealous of his quick rise to fame and his ample success, but some may not have wanted to recognize that someone not from North America or Europe had made such a monumental.

of cases of Shaugas disease where Kraus had found none. Yeap, okay, Yeah, I think in one of the publications Shagus like kind of hinted about like, oh, well, you might not really have the right technique for scope, you know, microscopy or whatever, and Matsa was the first to suggest that the taypanosome could be transmitted through blood transfusions, which were slowly improving and becoming more accessible in like, you know, thirties and forties.

Maza's work showing widespread prevalence again kicked things off for Shaugust disease research as more and more researchers became aware that it was this tip of the Iceberg type of situation.

Increasing development, deforestation, and urbanization throughout the mid twentieth century led to both this increase in disease prevalence as well as the construction of hospitals where the chronic manifestations of the disease and congenital transmission could be more easily studied, especially as technology improved to actually see what was going on inside, like with your heart and with mega colon

and so on. Chagas's son, Evandro followed somewhat in his father's footsteps and played a big role in uncovering the widespread and hidden nature of the disease and the little girl Bear Nice Chaugus's first Shagus patient was found again at the age of fifty three, still with circulating trepanosomes, but no sign of disease. Oh good, Yeah, yeah, she died I think at the age of seventy or seventy eight, maybe with I think seventy eight, with no relation to Shaga's disease.

being of the people that they studied. For example, in an instance of medicalized torture in Texas, a researcher named Ardzruni Pakshanian crushed some kissing bugs and smeared them into the eye of a black man in his twenties who was likely a patient at Austin State Hospital formerly known as the Texas State Lunatic Asylum, just to study the progression of disease and how long this person would remain with like circulating parasites.

But yeah, the study continues to be cited. What I know, Carlos Shagas recognized all the way back in nineteen oh nine the public health relevance of American tripanisamiasis, but it wasn't until the nineteen eighties that countrywide surveys were conducted using standardized protocols and a reliable estimate of the number of people infected and at risk could be even estimated, and those numbers were often shocking. I'm not going to go through all of them, but you know, I'll throw

a few out there. So from like twenty percent in Bolivia to twenty percent of rural Chile and up to fifty percent in parts of rural Venezuela, Shagas's was a much bigger problem than I think anyone had any idea about.

And this growing awareness of the enormous problem that shagas disease poses did help lower the incidents of disease in some places, such as through like the Southern Cone Initiative and other pushes for eradication and control, and the existence of the somewhat effective drug that's used I think it's benz ny dazzlely close to it, which was introduced in nineteen sixty six. These things also helped, but we're still a long way off. Yeah, but exactly how far off are we? Aaron?

after this break. It's interesting, Aaron, because despite just how when you think about it, just how inefficient the transmission cycle really is in terms of trying to get the poop of this bug somewhere near a bite wound, the overall ecology of this disease is so complex, with so many different wildlife and domestic mammal species involved, and in humans, the infection can persist for so long that this is not only a very difficult disease to control, but estimates

of incidents and prevalence are also very difficult. Right, But we'll do our best here.

living with Shaugus disease currently. And what I don't know, because I see your face thinking, HM, is does that mean six to seven people living with some amount of illness from shaugust disease or six to seven million people living with tripanosomacrusie in their bloodstream? Right? And I imagine because that number is from the World Health Organization, that that means people with some amount of disease. Okay, okay, But what's worse than that number? Sixty seven million people,

which is probably an underestimate. That's pretty bad already m hm. But it's estimated that only one to two percent of those people living with shaugust disease have access to treatment.

That's the problem. That's a huge part of the problem, right, right, So you have to be able to find people before they have heart failure from chuckus And like we've touched on though historically this is a disease of poverty and of Central and South America and the southern part of the United States, we live in a globalized world and

because of global migration, this is a global disease. And like you touched on Aaron, in non endemic areas like Europe and much of North America, physician knowledge of the disease is seriously lacking, and it's thought that cases are underdiagnosed by like ninety five percent is one of the estimates that I saw.

billion dollars annually. That's more than rotavirus, that's more than cervical cancer, that's more than lime disease, and results in an estimated over eight hundred thousand disability adjusted life years annually.

researching Shagas disease from every single angle. At this point, as far as I could tell in my research, there aren't any novel therapeutics that have made it very far in the research chain. There are a couple of different avenues for promising vaccine research, both in preventative vaccines, so vaccines to help prevent the disease, as well as therapeutic vaccines, which would be something to help prevent the development of

chronic disease. But as far as I could tell, these are all in pretty early stages of development, and one of the biggest issues is funding. And then of course people are really starting to realize the impact of non vector borne transmit roots such as congenital infection and how little we know about that. So suffice to say, there's

a lot of different research needs. Oh yeah. For that reason, we wanted to talk to somebody who has done research on a lot of different aspects of shaugas disease, from trying to better understand the dynamics of shaugus here in the US and involves citizen science, which is so cool, to really nitty gritty molecular biology to better understand the vectors and the pathogen itself and so much more so, we wanted to talk to someone about all of these

lingering questions that we have regarding shaugas, and for that we turned to one of our faves, doctor Sarah Hamer.

depending on the host that's infected. Sadly, we don't really know about the impact on a lot of different wildlife species that are infected because it's hard to come, you know, to find them, it's hard to get money to study the clinical outcome or to follow them forward over time. It's hard to do that in nature. The nice thing is, you know, from what we can understand, what we know, disease seems to look similar to what it does in humans.

We know the most about the disease outcome in dogs, in non human primates, and in humans, just because that's where the most amount of clinical attention has been paid. So just we see in infected humans, what we see in these infected animals is that there can be a subpopulation of infected animals that might not ever develop signs of disease. They might remain asymptomatic for life. So that's

a very good thing. But there is you know, some percentage, some unknown percentage of affected animals that will develop disease, usually heart disease, and depending on where the parasite affects the heart, we might see different you know, outward manifestation of the infection. So you know, just like humans, we can see inflammation fibrosis of the heart depending on you know, exactly where the parasite localizes in the heart. This can

lead to you know, acute problems. This can lead to chronic problems in the animals, especially with fis of heart failure. We see sudden death. Often young dogs can die suddenly from this infection. We're working now to try to figure out, you know, if there's an infected animal, what are some

ways that we can predict the outcome of infection. Is this something we need to be worried about versus is this something that the animal will be able to live with this infection for life and we don't need to be as worried about it.

and then the risk of exposure to humans. So let's start with the domestic side of things, which domestic animals play a role in the infectious cycle, and what does that role look like And are there some domestic animals that contribute more than others to the risk of exposure for humans.

attention than like feline shogga disease. But what I'd like to start by saying is that there's no evidence that infected dogs or infected cats pose a direct transmission risk to people. So even if you knowingly or unknowingly own a dog that's infected, for example, that sort of direct

risk dog to human transmission hasn't been shown. Instead, the role that infected dogs might play is that they could potentially infect kissing bugs that feed on them, and then those kissing bugs that are around the home could be a source of infection to other animals or to people.

So when we think about, you know, domestic animals and their role as a reservoir, by reservoir here, we mean that it's an animal that not only gets infected, but it gets infected and can kind of sustain that parasite in its body and then serve as a source of infection to another animal or two in this case, to a vector that's feeding on it. And dogs can certainly play that role. It's actually really hard to figure that out, though.

It's not as simple as just figuring out if an animal is a reservoir by taking a blood sample and doing a molecular test and Yep, the parasite's there, it's a reservoir. Instead, the approach that we've used, you know, in our research settings at least to define the role of dogs as reservoirs is that we can sample their blood and then bring that blood to our kissing bug insect colony that we have on campus, and then we can feed the blood from the dogs to clean insects

in a very controlled environment. We can monitor those kissing bugs for infection to see if they become infected and will shed the infection in their feces. We can do that days, weeks or even months after they've been fed

this potentially infectious blood meal. So it's through you know, some really neat techniques like that that we can begin to define who are the important reservoirs in domestic environments or in wild environments, and that you know, helps us understand the ecology of this disease better.

to our lab for part of our research. So this really started, you know, out of desperation because we were out doing fieldwork and these insects are really hard to try app using standardized traps, you know, manual fieldwork to find them can be pretty labor intensive. But we were trapping on these Texas ranches and other areas and the landowners would tell us, oh, yeah, I've seen those insects before. Oh I've you know, I've captured a couple of those.

I saved them, you know, and they might have them in an old pill jar in the freezer. And so it was really through that that was the start of our community science program. And it's it's definitely a two way street. You know, we want to provide a lot of good info. We do that through our website, through a smartphone app, through printed brochures and outreach seminars that we give and then in return. Since twenty thirteen, we've received over eight thousand kissing bugs from people in twenty

seven different states. Then they've submitted these insects to our program and we can learn a lot. And basically at the state level, this community science program has replicated, you know, what's known of the historic distribution of kissing bugs in the United States and has provided just a wealth of great material for our research program. So from the community science program, we've learned that on average, it's just over

fifty percent infection prevalence of these insects. So of all the insects that we've received from community members that have submitted them to our program, will we will dissect them, take their gut material out, do DNA extractions, and then try to figure out if they're infected with the parasite or not. And we've found over fifty percent of the adult insects are infected with Trapanosoma cruisy, so pretty high

infection prevalence. And then furthermore, we've learned that there's two major genetic variants of the parasite that we find in kissing bugs of the United States, and we're kind of mapping out those genetic variants and trying now to figure out if there's different health consequences when people or animals

are infected with one type or another. But the most exciting thing I think that we've been able to do with these community science submitted kissing bugs is what's called a blood meal analysis, where we can taken individual insect and figure out what has it fed upon, what type

of blood meal did it get from what species? And this is really important for not just understanding the ecology of the disease, but trying to open the doors for management, because if we can figure out what types of animals are important for feeding kissing bugs and maintaining their populations, then maybe we can try to manage those species so

they have less contact with the vector. So just a glimpse of some of our data from blood meal analysis of these community science kissing bugs, we find, overall about half of them have evidence of feeding on a dog. And that makes sense because we know that a lot of these bugs submitted by the public are actually found in dog kennels or in areas where their dogs sleep. A lot of people submitting bugs will report that they

own multiple dogs, so that makes sense. We also find that kissing bugs have fed on cats, chickens, tortoises, a lot of it is, you know, just depending on the habitat where they're found, whatever the most abundant host is there, that's what they're going to feed on. Like you know, kissing bugs collected from a chicken coop, they're gonna feed

on chickens. But we also get some exciting observations like tigers, and that was found from some bugs that were submitted from the local zoo, so it makes sense that that host is available and the bugs will happily feed on it. And two of my favorite observations was an elf owl. We found evidence of a kissing bug feeding on the elf owl, which is the world's tiniest owl. And this was a bug that was collected by a community member from Big Bend National Park where these elf owls will nest,

so that was pretty neat. And then a more recent one was our results from Bloodmaal and allis was a peach face love bird and we thought lovebird, like, this isn't a wild species, you know where this insect was submitted from. So we wrote back to the submitter and we said we're trying to make sense of this, you know DNA sequence that we got, and she wrote back immediately and said that's my pet lovebird that I have

in a cage in the house. And so this, you know, this technique can really open our eyes for just how flexible these kissing bugs can be in what they feed on. And this was all enabled by our community science program.

So which wildlife species are considered the most important reservoirs? I know this changes a lot geographically as well, But are there some you know, more than others that seem to be, you know, play the largest role And you know, I also wanted to kind of ask you about how things like deforestation and land use change is impacting Shauga disease in wildlife and then thus exposure to humans.

to a lesser extent, other rodents or bats. But very little research has been done to really rank their importance, to figure out what is the exact wild species that's the most important reservoir in this area or another area. In terms of you know, your question about land use change and you know, deforestation or other types of land

use change that's occurring. You know, of course, we know there's some pretty cool and compelling stories from different vector born diseases that would say that certain types of deforestation might really increase transmission, for example the lime disease system. I think it's a little premature to understand exactly how deforestation or other land use change is likely to impact

the ecology of Chogga's disease. These try it means, you know, they're not just found in silvadic or natural environments or more rural environments. We also regularly find them in urban areas, for example, lots of collections from San Antonio, Dallas, Fort Worth, some of these major urban cores here in the South. So they're flexible in where these different kissing bug species

can thrive. But certainly, you know, if we have changes to the landscape like deforestation, that might make that area more or less attractive to the raccoons or the possums. Who really can thrive in small forest fragments adjacent to human dwellings. And so maybe if we're changing the landscape in a way that makes it more attractive to some of these medium sized mammals, then we could have even more, you know, more of these reservoirs across the landscape that

could increase transmission risk. But we can imagine scenarios where the opposite could be true as well.

The parasite can effect virtually any mammal species. So it's sylvatic, and it involves a lot of players in the transmission cycle. So it's not as simple, not that it's simple, but you know, when we think of a different vector born disease, you know, human malaria, for example, main reservoir would be humans, you know, certain mists, dospecies. In comparison, here, we've got just dozens of species that need to be considered in the management of this disease in nature. So it's sylvadic.

The second big challenge that comes to mind is just this relative lack of awareness, lack of medical awareness, lack of veterinary awareness for chagas disease tapanism a cruisie. This is neglected from medical attention, it's neglected from research communities, and so it's you know, it's typically, especially when we're thinking about shagas disease in the United States, it's quick to conclude, oh, this is you know, this is a

problem elsewhere, this is a problem across Latin America. But we've got these endemic kissing bugs, and we've got infected wildlife and we have spillover transmission to humans and to our domestic animals that are causing big problems. But because there's not more attention, we're not testing more. So we don't have a good understanding of, really, especially from the veterinary perspective, how many animals are impacted, what species, you know,

what are the impacts for their health? And without those numbers to show just how many animals are impacted, then you know, it's hard to convince big granting agencies to put more money towards this problem. And so I think the overall lack of awareness is one of the biggest challenges for this disease.

and the same would be true. Our app is available for Apple and Android from the iTunes Store and Google Play and you can download that there and has the same capability as the website.

from two thousand and four. A nine thousand year old record of Shagas disease by Clement at All twenty twenty out of Africa, the origins of the protozoan blood parasites of the Tripanosoma cruisy clade found in bats from Africa, and by stever Ding from twenty fourteen, the history of Shauga's disease, and a whole bunch more that'll post.