On one burning day in April, in a village in Biha, Sushila Devy was worried about her sick child. Her decision to seek medical help required brave determination. There was the overpowering heat through which she would have to walk, carrying her sick child most of the eight miles to the
government health center. The child was ill, but not emergency ill in any of the too familiar life threatening ways, the acute fever and coma of childhood malaria, the rapid wasting diarrhea and death of cholera, or the labored gasping of pneumonia. It was merely that the child seemed somewhat feverish this past month and was becoming emaciated despite a reasonably good appetite, with a distended abdomen. The young doctor was brusque, unfriendly, and uncommunicative. He told Sushila to put
her frightened child on the bare wooden examination table. To the doctor, the constellation of signs and symptoms could point to only one diagnosis. The prolonged fever, the greatly enlarged liver and spleen, the anemia, the serum that jelled when mixed with formaldehyde all meant visceral leshmaniasis. Realizing the gravity of what he was about to tell Sushila, his pomposity fell away. Mother. He said, gently, your child is very ill with kala azar. It does not mean death. Your
child can be cured. You must buy medicine. Then you must come here every day for twenty days so the nurse can inject the medicine. How much is it, Sushila asked fearfully, for you, I will give you a bottle of the drug enough for her whole treatment for three hundred rupees about fifteen dollars. It was an astronomical sum, more than the family's income for some months. Sushila picked up her child and began the long walk back to
her village. Even if by some miracle they could buy the medicine, there was no way that Sushila and the child could travel these long miles to the health center for twenty consecutive days. No for the child, they would have to do the best they could. They would pray to the gods, they would consult the doctor in the adjoining village.
In the end.
As the weeks passed, the child became progressively more ill. She grew even more emaciated, her skin turned a dusky gray, her hair became brittle, Small bleeding sores covered her body, and the abdomen, burdened with a grossly enlarged liver, distended even further. One day, some three months after Sushila's visit to the health center, the child began to cough and gasp for breath. During the night, the little girl died,
a fragment of life sacrificed for want of fifteen dollars. Ooh, that was rough to even read out loud.
Yeah, that is from a book called The Malaria Capers by Robert S. Desowitz.
Hi.
I'm erin Welsh.
And i'm erin allman updyke.
And this is this podcast will kill you? It is.
It's a depressing one today, erin.
I mean, when are they not?
Yeah? Could we ever, like maybe one time this season we could find a not depressing one just to try.
We could try. Oh gosh, So, as you may have guessed, this week we are covering leshmaniasis, which includes not just visceral leshmaniasis as described in the first hand account, but also cutaneous and muco cutaneous leshmaniasis.
Sure does.
It's a lot more complex of a story than I think we.
Realized really really complicated, a lot more than I ever knew.
So it was good to learn this stuff. But also, oh my gosh, I hope that I do it even a shred of justice.
I trust you, Oh gosh, I trust you well. Erin, I think we have a couple pieces of business to take care of, or at least one.
Yep, is it that it's let me check quarantiny time.
It is, indeed quarantine time. You are absolutely exactly right.
What are we drinking today, Erin?
Today we are drinking a sand fly in the ointment he oh so.
Named, because this is a disease transmitted by sand flies.
And in sand fly in the ointment there is lime juice, grapefruit juice, some simple syrup, all spice liqueur, so I finally get to use that stink and all spice liquor that's been on my shelf for ages, and some rum yum. Yeah. And we will post the full recipe to the quarantine as well as the non alcoholic place Barrita on our website This podcast will Kill You dot com, as well as all of our social media channels, so check it out there. Yeah. Any other business that we have I don't believe.
So all right, then shall we just dive in season four, episode two?
Oh my gosh, let's do it, okay.
Right after this break. So, like we mentioned already, the biology of this disease is quite a lot. So I tried really hard, which is the opposite of what I normally do in my notes. I tried to really keep this organized so that we can go through it in a way that makes sense. Okay, So let me just go ahead and get started, all right. So, leshmaniasis, like you mentioned already, aarin, it's not just a single disease.
It's a group of at least three different disease syndromes which are caused by a number of different species of protozoan parasites in the genus lesh Mania.
It's kind of interesting that like they're all like when we say leshmaniasis, it's like means all of them. It means so many different types of diseases and so many different like caused by so many different species of parasites.
Yeah, like overimplification. Yeah, yeah, I can't believe that we call this all the same disease. Quite honestly, it blows my mind.
I mean historically we didn't, but we'll get to that.
Oh any great, I can't wait. That makes a lot of sense actually, okay, yeah, so at least twenty different species of protozoan parasite transmitted by a whole number of different species of insect vectors. In this case, like we said, we're dealing with a new type of insect vector that we haven't dealt with on the podcast before, and that is the sand fly.
Yeah, this is our first new vector.
Yeah, we've only done mosquitos and ticks so far.
How interesting. I didn't realize that.
Yeah, so that's fun. So sandflies, for anyone who's not familiar, they're another sort of biting fly similar to mosquitoes. It's primarily the females who take blood meals, whereas both males and females also feed on like fluoral nectar and sugar water. So in this case, we're talking about sandflies in two different genera, Lutzomia and Phlebotomus. Okay, so so far we have over twenty species of parasite and two whole genera of sandfly.
Okay, it's a lot.
Uh huh. It's gonna get to be more. Because leshmaniasis affects humans, which is what we're going to talk about today, but it also affects like at least one hundred other mammal species. So in addition to different forms of the disease that we see in humans, there are different cycles of the disease. There is a zoonotic cycle of disease wherein humans become infected from vectors that got infected from animals,
so from animal to vector to human. And then there's also anthroponotic cycles wherein humans are the dominant reservoir host and humans are infecting other humans through a vector.
And it's not just mammals, right, isn't it also reptiles.
I think that reptiles and some birds have been known to be infected. How much of a role they really play in the zoonotic disease in humans is pretty minimal as far as I know.
Yeah, I don't think they do, but I think it is just amazing the sheer number of species I know a different, like very different groups of animals that it's these parasites can infect bananas truly.
So yeah, okay, that's a lot already.
Okay, yep, So for.
This biology section, because that's so much, we are really going to focus on the disease or the three big disease states of leshmaniasis in humans. I'm not going to touch on leshmaniasis in animals because it's just going to make things more complicated. So let's get into this disease by going over the parasite life cycle, which will tell us how it's transmitted, and then we'll talk about how we see the disease mana fest in humans.
Okay, sounds great.
So leshmania species the parasite that causes leshmaniasis, like plasmodium parasites that cause malaria or tripanasoma parasites that cause Shaggas disease, are a eukaryotic, single celled parasite that has multiple different distinct life stages in their different hosts, whether a mammal or reptile and insect. In the case of leshmaniasis, they have two different forms, the a mastigote and the pro mastigot.
One is a little ball that lives inside of our cells, and one is a cute, little kind of spermy shaped thing. I yes, maybe that doesn't sound cute, but it is with a little flagella tail that can swim. Okay, So a leshmania life cycle goes something like this, a sand fly takes a bite of an infected animal host in just a blood that contains the a mast goat form
of the parasite. Those parasites travel through the gut of the sandfly, transform into the pro mastigotes, which have that flagella and can swim, and those parasites continue to divide. They make their way out of the gut of the sandfly and into their proboscis, which is the biting part of the fly. And then when that sandfly takes another blood meal, those parasites are regurgitated into that new host. In that host, let's say it's a human, since that's
what we're talking about. Those pro mastagoats which are swimming are taken up by our white blood cells mostly are macrophages, which we've talked about a lot on this podcast. Those are a white blood cell that usually helps clear infection by like engulfing bacteria and parasites and killing them. Turns out, in the case of lesh mania, when a macrophage ingest it, that's actually where they become a master to goats and then continue to divide and reproduce.
Yeah, so how do they avoid death?
Oh, such a good question. Aaron, I wish that I had a full good answer to that. So leshmaniasis is a disease of what's called the reticulo endothelial system, So that means that it effects and replicates white blood cells, especially macrophages, and then affects in theory any organ where those white blood cells tend to congregate. So the exact mechanisms by which it evades our immune response are really really complicated To kind of sum it up in the simplest terms that I can, Gosh.
Is it basically suppress the immune system overall?
Exactly it it's press our immune system? And how exactly they're able to survive inside of macrophages, I don't fully know. But by living inside of macrophagis they evade any other of our immune responses?
Okay? That makes sense and also very sneaky.
And very very sneaky. Okay, And overall we know that infection with leshmaniasis it causes our body to mount an immune response, like we make antibodies to it, but those antibodies don't do much. It turns out that to develop immunity towards leshmaniasis, it's more about cell mediated So you need a strong t cell response to eventually kill those macrophages that are infected. Does that make sense?
That does? And so basically the ant because it lives intracellularly, the antibodies don't even reach them.
Right, Yeah, exactly. But yeah, overall infection with lesh mania species decreases our overall immune response. Okay, so there's really strong interactions going on between this parasite and our immune system, which is fascinating and complicated. Yeah, so let's get more complicated, all right. Like you mentioned, Aaron, there are three major
forms and some others actually that we'll touch on. In terms of the disease that we know of as leshmaniasis, there's cutaneous, mucosal or mucosal cutaneous called a couple different things, and visceral. What type of disease a person gets depends on the parasite species. So some species generally cause a
visceral leshmaniasis, while others generally cause cutaneous infection. But it also depends on host factors that we don't fully understand, whether that's genetics like genetic susceptibility, or overall immune response. Like if you have a poor cell mediated immune response to begin with, you might be more predisposed to infection, et cetera. So it's complicated. That's that's the subtitle of this episode.
I was gonna say lash mania relationship status. It's complicated.
I like it.
So when you say generally this species causes visceral versus cutaneous whatever, what does that generally actually look like? Is it like ninety five percent? Or is it much? Is it more variable than that?
Very good question. I don't have a solid number on it. So in most of the literature, for example, visceral leshmaniasis is most often caused by leshmania donovanni, but also by leshmania in phantom, which is also kind of the same thing as leshmania shagasai. Okay, those are the same thing, seem to be the same species. Okay, So those two
species are the dominant species that cause visceral leshmaniasis. However, in a few cases, a couple of other species have been found to cause visceral leshmaniasis that normally cause cutaneous The rest of the species tend to only cause cutaneous leshmaniasis except in those cases. Does that answer your question?
Yeah? And then what about muco cutaneous?
So muco cutaneous will get into it tends to be a longer term consequence of cutaneous leshmaniasis.
Oh yeah, and that but that is also associated with I assume some parasitic species more than others.
Yes, yep, exactly.
Okay, So like, okay, okay, interesting.
Yeah, it's very interesting. And I fully did not know that before researching for this episode. Like I knew there was cutaneous and visceral, but I did not know that they were caused by two different species, and that was what distinguishes which one you get for the most part. Yeah, yeah, but it's got to get more complicated, of course, because some people can be infected with either the species that cause cutaneous or visceral leshmaniasis and be entirely asymptomatic. Yeah, okay.
For infection with cutaneous species, it's generally about ten percent of people are asymptomatic. Whereas, and this is really interesting, asymptomatic infection with species that cause the disseminated visceral infection really varies depending on region, but not necessarily depending on species. What this is so much aarin that implies.
I don't know what that implies.
I don't buiere. Okay, hold on, So.
In the people who are asymptomatic but infected, is the parasite, like, what is it doing in their body?
Good question?
I wish I knew, Okay, And do they do? They go through like a course of infection assent where it's there and then it's gone.
They mount an immune response. Okay, So what exactly does that mean?
Because immunity, as we'll talk about more later, increases with age, which likely has to do with repeated exposure eventually producing long lasting immunity. So in a lot of cases, it's not necessarily like one exposure and then boom your immune it's like repeated exposures, especially for cutaneous leshmaniasis. So what's happening? How many times could you be infected and be asymptomatic? It's also let's throw some more complex things in there.
In all cases of leshmaniasis, the incubation period is very long, Okay, We're talking weeks to potentially months. So are people asymptomatic entirely or are they asymptomatic at the time that we test them to see if there have any evidence of parasites, but then many months later develop infection maybe for some portion of people. So in all three of these cases, cutaneous, mucocutaneous,
and visceral leshmaniasis. These parasites are infecting macrophages. The clinical disease that we see depends on where they localize and whether or not they disseminate to the rest of your body and cause like a systemic infection. Okay, yeah, okay, So let's talk about the symptoms that we see. Cutaneous leshmaniasis, which is the most benign of the three. So that's what we'll talk about. And benign, by the way, does
not mean that it's not severe. It can be debilitating, it can be extremely scarring, and as I'm sure you will talk about aaron, it's associated with a lot of stigma, but it just kills people less than the other reforms.
Yep.
So it's generally caused, like I said, by a number of different species of leshmania. The most common species are Leshmania mexicana, Braziliensis major and tropica, but there are a whole bunch more like thirteen or fifteen or something more. And cutaneous is exactly what it sounds like. It affects
your skin, so it causes a more localized infection. It usually starts as what looks like a bug bite from where the sandfly bits someone, but it doesn't heal and over a long period of time, and the length of time depends a lot on the species, so we're talking anywhere from two months to fifteen months. This lesion where this sort of bug bite was begins to ulcerate, and it eventually leads to it can lead to pretty significantly large ulcers like open sores essentially, which from what I've read,
are painless, but they look very painful. And then this is a localized and self limited infection. So generally these ulcers, over the course of weeks and months, they begin to heal via granulation. So like our normal body's healing process eventually kicks in, but it takes a really long time. And that's probably because as much as our body is trying to fight off this parasite, it's inside of our white blood cells, so it's really difficult for us to
really fully eradicate this quickly. Yeah, And these ulcers lead to significant scarring. So the scar is generally a depressed and large like the size or a little bit smaller than how large the ulcer was scar and that can be very debilitating. Depending on where it is, it can be disfiguring and be associated with significant stigma, especially if it's on the face, which something like fifty percent of sandfly bites tend to be on the face, just because
it's easily exposed. We don't generally have clothing on our face. So yeah, so that's cutaneous lashmaniasis. You can also imagine that since this is an open wound, you can get a secondary bacterial infection on top of it. Yep, which can lead to more complications.
I'm starting to feel like Benign is not even coming close to accurately describing.
Those It's not. It's just of these three, it is the least deadly.
Okay, how about that?
How about that?
Okay?
So next is mucosal or muco cutaneous leshmaniasis. This is a very destructive form of leshmaniasis that most of the time occurs after cutaneous leshmaniasis. It's most commonly associated with Leshmania braziliensis. Like you asked which species erin, but there are other species, Especially in people who are immunocompromised and don't have a good cell mediated immune response, then you
can get mucosal leshmaniasis from other species as well. So this form of leshmaniasis presents often with nasal stuffiness, nose bleeds, sloughing off of tissue from inside your nose or mouth. It can result in erosion of any of your mucosal surfaces, so inside your mouth, your cheeks, your nose. Kind of the worst thing that can happen is it can essentially eat away through your nasal septum and completely destroy your nose.
So it can be very disfiguring. And if it's associated with your trichia or epiglottis, for example, then it can cause respiratory compromise. So this form can be deadly, especially if it affects the mucosal surfaces that we use to breathe, for example. So that's depressing. Now let's move on to the most depressing and that is visceral leshmaniasis, which is also known as kala azar, which is Hindi for black fever. And that's what you heard in our first hand account.
Like I mentioned earlier, it's most often caused by leshmania donovanni, but also leshmania in phantom and or shagasai, which are the same thing. And this is a truly horrible, horrible disease. I think that our first hand account did a lot more justice than I'm going to to describe just how awful it is. Clinically, what we see is a very slow, insidious over weeks to months where you have this fever
and general malaise, just not feeling well. You have significant weight loss that leads to what we call cachexia, which is just like emaciation. Okay, But then on top of that, because this parasite is in our white blood cells that congregate in our spleen and liver, you get massive splenomegaly, so enlargement of your spleen, or hippatosplenomegaly, so enlargement of
your spleen and liver. And because the other place that our white blood cells congregate is our bone marrow, this can lead to massive infection in your bone marrow that causes pan cytopenia, which means all of your bloodlines are depressed, so you're anemic. But also all your white blood cell count are very depressed, which means, as you can imagine, people are very susceptible to secondary infection because they have
no immune defense. Essentially, visceral leishmaniasis is almost uniformly fatal if left untreated. Mortality is ninety five to one hundred percent.
And is it caused typically by the parasitic infection directly or through secondary infections.
Both, and I don't have a number on the exact percentage of which is which, but absolutely both are cause of death. Yeah, and leshmania Donovani. Like I mentioned earlier,
there's kind of two different cycles of this disease. There's the anthroponotic, where humans are the main reservoir, and then there's the zoonotic where it's animals, whether domestic or wild, that are the major reservoirs for infection, and the main species that causes visceral leshmaniasis is also considered anthroponautics, So humans are the major reservoir rather than animals, right, Okay.
Do you have a timeline specifically for muco cutaneous how long it takes for cutaneous to turn into the mucosal variety if it's going to go that way?
Very good question. I think a lot of what I've seen is up to like six months or even a year or more after initial infection is when you can end up getting muco cutaneous or mucosalleshmaniasis. Yeah, gotcha, there's a little bit more. Okay, So I said there's three main syndromes of disease, but there's actually two others too, So there's a form called diffuse cutaneous leshmaniasis, which, as you can imagine, is like cutaneous leshmaniasis, but instead of
one single ulcer, you have many. This is thought to be kind of an autoimmune related disease. It's not entirely clear why some people get it and other people don't, but essentially what happens is those parasites travel through your lymph system along lymph lines and can cause still a cutaneous only so it's still just in your skin, but a more widespread infection than just one single ulcer.
Huh. Okay.
It's also possible, though, to get multiple ulcers at one time, just from multiple sandfly bites, so this is more diffuse than just that. Okay.
Can you have both visceral and cutaneous at the same time from like different species?
You know, that's a really really good question. I don't know because I didn't ever see that anywhere, but these happen in the same locations, so I don't see why not.
And like if immunity seems to develop over multiple exposures over time, right, and let's say that you, like, are you immune to just the cutaneous forms or like the ones the parasites that cause the cutaneous form, or are you also protected from visceral.
It's this is a very very good question, and it's one that I still don't fully understand the answer to because of how complex the immunology of this is. I think that immunity is at least partially cross protective from what I understand. But that's why when we'll talk about vaccines, it's so important to develop a vaccine that results in immunity to multiple species of leshmania.
Yeah, okay, I mean the vaccine things seems very difficult to.
Oh my gosh, you have no idea. Okay, okay, there's one more disease that we have to talk about. We're not dying, and that is post kala azar dermal leshmaniasis.
Oh my gosh.
So let's break that down. Post kala azar So this means after someone survives kala azar, which is visral leash niasis. So that means someone who has been treated and successfully supposedly cured of cola azar dermal leshmaniasis. So now this is a skin manifestation of a prior visceral infection.
What what does that look like? How does that happen? What proportion of cases does this happen? Like?
Yeah, great questions. So the weirdest thing about this? Okay, first I'll answer what does this look like? It actually looks a lot like leprosy.
Oh interesting, okay, yeah, So.
It causes these kind of nodular lesions that can be throughout kind of all of your skin. Now who gets it and what proportion? This is very bizarre. It generally has only been described in certain regions, so in the Horn of Africa and in South Asia, not in Latin America, where we also see a lot of leshmaniasis.
So in for.
Example, Sudan, about fifty to sixty percent of people that were treated for visceraa leshmaniasis went on to develop post cola as our dermal leshmaniasis. And this usually happens between six months and a year after infection. Why does it happen? I don't know aarin. And in South Asia the incidents is much less, It's like five to fifteen percent and the interval is often longer.
Is the treatment different like the most common treatment used?
Good question overall, so we can talk about treatment.
Sorry, no, no, don't be sorry.
So first I'll say that what we do know about this is it seems to be a reactivation of the infection. That is, people who present with PKDA post cola as our dermal leshmaniasis are infectious to sandflies, so they have parasites still in their system. So this suggests that whatever treatment was used didn't really eradicate that infection in their bodies erin, So what do we do to treat it?
Okay, my face is like uttershock and confusion.
That's how my face has been through all of this reading. Okay, So, for a long time, treatment for both visceral and cutaneous and mucosal leshmaniasis was with what's called pentavalent antimonials. Okay, that's just a fancy term for the specific drug that was first used to treat leshmaniasis. As was mentioned in our first hand account, this drug requires daily administration via injection for anywhere from twenty eight to thirty days, so it's a very long course and it requires a healthcare
provider to be able to give those injections. And nowadays resistance is very widespread to these drugs. Oh my god, So those that are not used as much anymore. Yeah, Luckily there are other drugs, but drug treatment for leshmaniasis
is a pretty major problem, as you can imagine. One drug that seems very promising and has been shown at least in some regions to be very effective, is liposomal amphoteraesin B. I don't know if you remember we talked about amphoterrasin B in the context of cystic fibrosis of all things.
Do you remember that, No, I have to be honest.
Now that's okay, you don't have to I just thought it was fun. Anyways, amphoterrasin B. It's an anti fungal, actually, but this specific formulation has been found to be effective at least in India and Bangladesh as a single dose cure. Really yep, one single dose, which is major. It's still an injection. You have to give it by IV, but
it's one dose. So not only does that make it less likely that we're going to develop resistance because you don't have to keep giving it over and over and over, but it also is great in terms of being able to treat people and not have to have them come back and back and back. But it is still really expensive.
And I've also read that a lot of people do not react well to it, like it has a very variable tolerance yees, and so you may not be able to take it at all.
And amphitereism B itself is a very very toxic drug, so this specific formulation is a little less toxic. But yes, for all of these drugs, the side effect profile is the side effect profile, and the cost and the root of administration and resistance, all those things are some of the barriers to treatment for leshmnisis there's a lot going on here.
The cost is unreal.
Yeah, there are a couple of other drugs. There is at least one oral drug, which is you can imagine being able to give someone a pill is a lot better than having to give injections. And that's mill to phocine. I'm guarantee I'm pronouncing that incorrectly, but anyways, that's an oral drug that was effective for a time, but now
there's massive resistance to it. So to answer your question that you asked about postcla as our dermal lashmaniasis, if different treatments are used in different areas, the answer is generally yes, we have all these different treatments available, but what is available in any given region can definitely vary, and what is still effective and or affordable in different regions also varies. So how much of a role that
might play in PKDL is a really good question. I imagine it must play a role because this is a reactivation of an infection, which means that our cure didn't fully cure.
Right.
So there's also a lot of interest in using combination therapy the way that we do for something like tuberculosis, which is also a very long lasting disease or HIV. So there are a lot of different drug combinations that are being used as well. So that's Is that long enough for you? That's the biology.
It's quite a long wow.
Yeah, my goodness. So here's the thing here, and I have a lot of questions for you. Oh boy, where on Earth literally and figuratively did this parasite come from? How are there so many that cause so many different diseases in humans? Like, just give give it all to me. I want to know what's going on.
Please, I'll do the best that I can. Right after this break, Okay, the history of leshmaniasis right off the bat, let me just say that these are some incredibly old parasites. Oh yeah, Like I'm not just talking oh ancient Egyptian papyri. Although I will get there. I mean, like millions upon millions upon millions of years old.
I am not surprised by that.
It's very cool. Okay. The sheer diversity of Leshmania species and the range of hosts that they infect gives us some idea of their ancientness. But did you know that Leshmania like fossils were found in the proboscis and elementary track of an extinct sandfly encased in amber from the Cretaceous period. Stop it over a one hundred million years old I'm sorry.
They found it in thescuz of a sandfly.
Yes, yes, yeah, one hundred million years old, and these are Leshmania like but they were probably like they were probably the ancestors of the current or present Lashmania species.
So we're talking like dinosaur infection.
Oh yeah. So this, this preserved sand fly was filled with reptilian blood, and the presence of a parasitic life stage of the parasite also in the blood suggests that this le that this Leshmania like species was actually a two host parasite, with one of the hosts being reptiles.
Oh my, yeah, I can't explain how thrilling that is.
So because like we we see a lot of the ancestors of parasites as like, oh, this had a mutualism with this and then it found an opportunistic host. But this parasitic life cycle goes back to like millions and hundreds of millions of years.
That's phenomenal, Like to have evidence of a dual host parasitic life cycle one hundred million years ago.
Yeah, like, ooh, I know, it's very cool.
That is fascinating.
Okay, but those aren't the parasites that we see today in humans. So let's talk about the origins of those guys, all right. Turns out it's not as simple as that of the episode. So, as you mentioned Aaron, as you went over, there are many different species of leshmania that infect humans, and they can be found all over the world, with the highest concentrations in the tropics and subtropics. But unlike many of the other pathogens we've talked about, their
current worldwide distribution wasn't caused solely by human travel. So a lot of the times we talk about how okay it emerged in Let's say that there was a pathogen that emerged in Africa and then it sort of dispersed out from there as humans traveled. This isn't the.
Case, is that because it infects so many other species.
Yeah, that's what it seems to be. That's what seems to be. Actually, most of the leshmania species that we see in the New World evolved there rather than being brought over from the Old World, you know, during Columbus era exploration.
Cool.
There is one notable exception, though, which is Leshmania shagasai, which is now thought to be, as we've talked about, synonymous with leshmania and phantom and they think and people think that was brought to South America about five hundred years ago during the European settlement, so by either the settlers themselves or their dogs.
Oh okay. Interesting.
And there are a few different hypotheses as to the geographical origin of the different species of leashmania, or like the different genera. And I'm not going to go into each one of these because, to be honest, I didn't fully understand the papers that I read.
That's how I felt about the immunology erin I'm like, ooh, but it seems to me that the take home is that the genus probably evolved in the Mesozoic era, so like two hundred and fifty two to sixty six million.
Years ago, oh my gosh, on the super continent Gondwana.
Okay.
And then after it broke up and the sandflies and vertebrate hosts migrated and then diversified and then evolved into the different you know, subgenera and species that we see today.
Wow. Wow.
So there may have also been some bearing land bridge crossing by some rodent hosts during the Eocene that led to the subgenus Leshmania being brought to the ne Arctic from Asia, which later gave rise to the American Leishmania species. So that honestly, I don't know what that means entirely, but I did know it when I wrote it. Okay, goodness, okay, okay.
So we've established that Leshmania is a very old like dinosaur old different Leshmania parasites have probably been infecting humans since before humans were humans, stands to reason, ancient descriptions
of Lashmania Alegians go back thousands of years. There's a tablet from the seventh century BCE that is actually thought to be copied from earlier text dating back to fifteen hundred to twenty five hundred BCE that describes something awfully close to a leshmania a lesion, And of course I have to mention legally the Ebers papyrus Ebers from fifteen hundred BCE, which mentions something called a nile pimple which seems to refer to cutaneous leshmaniasis.
Okay.
And then there's the famous Persian physician Avicenna, who lived in a tenth century BCE, and he also described something called balk sore from northern Afghani the stand, which sounds a lot like the dry lesions caused by leshmania tropica. Okay, okay. And then as far as South America goes, there are some pre Columbian ceramics from around the fifth century that depict disfiguring facial conditions that seem to suggest the presence of uco cutaneous leshmaniasis.
Wow.
All right, now, if you prefer physical evidence and mummies over tablets and papyri, we've got you covered. A study of forty two Egyptian mummies dating from around twenty fifty to sixteen fifty BCE found DNA from leshmania, probably Leshmania donavani, in four of the mummies, which means that visceral leshmaniasis was likely present in ancient Egypt.
Whoa.
Yeah, and on the other side of the ocean, researchers have found leshmania DNA in a Peruvian mummy of a six year old girl data from eight hundred PCE. And because some types of leshmania can leave traces on bones muco cutaneous, namely, we can see the physical impact of leshmaniasis on skulls found in Chile dating to the eleventh century. Whoa, which would indicate the presence of mucocutaneous lesh along with those pre Columbian pottery.
Oh my goodness.
Yeah. It's kind of difficult to assess or to describe just how much of an impact that leshmaniasis may have had on the establishment of like a village or a city in a particular area, or whether there were significant outbreaks associated with one of the types of leshmaniasis. But we do know for sure that humans have taken note of the different forms, which gave rise to many different nicknames, and in some cases it altered their behavior to try
to prevent the disease. For instance, when the Spanish invaded South America in the sixteenth century, they noted that in the Peruvian Andes, disfiguring facial conditions were common among the coca growers who worked on the lower slopes, and that usually either people who were enslaved or of a lower social class tended to be the ones that worked at
these lower altitudes. So it's sort of like there was It seemed to suggest that the risk of working at lower altitudes was known, and over the years some researchers have suggested that Incan settlements tended to be restricted to highlands and avoided in the lowland forest out of fear of leshmaniasis. But I read a note that an article or a note in response to an article that actually
seems that it's probably not the case. Seems to be based on a few false assumptions that wet tropical valleys and rainforests were empty of archaeological ruins, which is actually just turns out that they're just more difficult to spot, and because the rainforest is like fairly resilient to some degree, anyway,
that makes sense, Yeah, all right. So some of the very first descriptions of leshmaniasis in modern times were made by the Scottish physician and naturalist Alexander Russell in the mid seventeen hundreds, and he described what was known at the time as Oriental sore, Aleppo, boil Bagdad, boil Jericho, buttons, et cetera.
Lots of different nicknames, all of these names that we don't use anymore uses them.
But basically what he was describing was cutaneous leshmaniasis, and he also described different forms, so a wet form and a dry form, which likely corresponded to either the zoonatic cutaneous lesh caused by Leshmania major and dry anthroponautic cutaneous lush caused by L. Tropica. And he also noted that the lesions tend to heal within eight to ten months, and that all the many different treatments existed, he felt that they often did more harm than good.
It's still true today for any treatments that are available, and.
He recommended doing nothing or at the very most apply a plaster of mercury, which I can't imagine would have been that great. But from the DNA analysis of those mummies from ancient Egypt, we know that visceral leshmaniasis had been around for thousands of years, but there doesn't seem to be any writings about it until the nineteenth century, which is interesting considering that it is pretty like unique,
or at least like recognizable. Yeah, and it also is associated with an extremely high mortality rate.
Yeah. So I wonder is it just that it's so prolonged of an infection that, like other I don't know that's.
Really this r I think it could be a few things. I think it could be, like you know, when I was when I was researching this, it was I would say, like a bit of a challenge to find good comprehensive historical descriptions of leshmaniasis. So I wonder if it's just
that we haven't been looking quite as as much. Okay, Yeah, But the other thing is that it might have been more localized, like it might have been, it might have not persisted in certain areas, like there does seem to be a lot of inter annual variation in exposure and in prevalence and so on, and so maybe it's just and we don't really know the reasons for that, because a lot of vector born diseases are just so dang
complicated in that way. Yeah, And so I wonder if that's part of it as well, is that it tended to be localized and then in other areas it may
have popped up but then disappeared. Okay, So yeah, yeah, and so in eighteen twenty seven, a military surgeon named William Twining published a full description of visceral leshmaniasis, which, as we've talked about, is known as kala azar, and it was found to be prevalent in certain parts of India, and throughout the rest of the nineteenth century, kala azar seemed to spread, popping up an epidemic form across much of India, and because of the way it's spread and
the timing of it spread, it earned the nickname government disease because it seemed to emerge. Yeah, it seemed to emerge whenever and wherever the British government established colonial rule.
I that actually kind of makes some sense in some ways.
Yeah, I mean I don't to be I don't know much about the ecology of sand flies and whether they're like whether certain species are more urban or like, whether there's what the association is with land use change and so on. But I really wonder if just just the the increased movement.
Oh maybe maybe we'll talk about it a little more than touch on that evstic plastic.
But yeah, So, during a highly epidemic period of around twenty five years in the second half of the eighteen hundreds, visceral lushmaniasis killed twenty five percent or more of the population in certain areas. What and more people fled, leaving some villages nearly empty. So like there do seem to be and there have been like a lot of you know, epidemics, But I think what's driving it is a very interesting question.
And while there can be epidemics of cutaneous lushmaniasis, I think that the extremely you know, and as maybe you'll talk about some of the more recent epidemics, the extremely high case fatality rate of untreated visceral lushmaniasis perhaps made these outbreaks more noticeable and alarming, especially since during most of the eighteen hundreds neither the causative agent nor the
vector had been discovered. Who Okay, As with many of the neglected tropical diseases that we've talked about on this podcast, can you guess what spurred on researchers to try to figure out the mystery of the different forms of leshmaniasis.
Were they like colonizing places and then dying because of it?
Yeah, precisely.
So.
The British presence in India in the eighteen hundreds and into the nineteen hundreds made leshmaniasis a priority for that country, and it didn't actually take all that long to uncover the secret behind the enlarged spleens and emaciation seen in some of the military that were stationed in some areas. In November of nineteen hundred, a Scottish pathologist named William Leshmann. Can you guess what he did? No, you can't guess what someone named William Leshman did.
Oh?
Oh, like he discovered the I thought you meant? Like how he discovered it?
Like?
That was one of the two obvious.
Questions in softball. There's ever been a softball Wait?
Try again, try again?
Okay, can you guess what William Leshman did?
Did he discover leshmania?
He did?
Oh?
My gosh, he yeah. So he looked at some samples from a spleen of a soldier who had died.
I was gonna guess he looked at spleen samples erin like, that's what I thought you were going for.
Oh oh, well, then you know I would have been so impressed.
Okay, anyway, sorry.
And then he also found the same parasites and experimentally infected rats, and so he reasoned that he had found the cause of agent of this deadly illness that he called dumb dumb fever, which is named after a town where he was working, called dumb Dum, like dumdum.
Yeah, oh gosh.
And he thought it was a type of trypanosome because he was like, oh, it looks like a little ovoid body. It's got to be a trypanosome. But then a few weeks after Leshman's paper was published, an Irish doctor named Charles Donovan don Vanni, he published similar findings, so ovoid parasite bodies in the spleen of an affected person. But he was like, no, this is not a type of tripanosome like this, It's just not. But I don't know
what it is. So he got a few more people involved, and ultimately it was the British medical doctor Ronald Ross who declared that these ovoid bodies represented a new species of parasite, a new type of parasite, and propose that they be called Leshmania Donovanni to give credit to the two major discoverers.
So at least they didn't name it after themselves. Someone else named it after them.
I think, I mean, even historically it didn't happen a lot, right that.
People named things after themselves. Yeah, I don't think so. Okay, you never know.
Someone tell us if we're wrong, because we're probably wrong.
We're often wrong the.
Majority of the time. Okay. I should note that there was a third discoverer who actually published his finding several years before Leshman and Donovan, a Russian scientist whose name was Pyotr Borowsky. Okay, but he did so in an obscure Russian language journal, and so his contribution was realized only long after the fact.
That's a bummer. That's English language bias.
It is.
Yeah.
The discoveries of the causes of cutaneous and muco cutaneous leshmaniasist followed pretty quickly after that of viscera lesh. In nineteen o three, the American pathologist James Homer Wright published a description of the parasite that he observed in a sample from a patient's sore. That makes sense, but he didn't immediately realize that it was a species of leshmania, But that would happen a few years later the recognition
that it was actually lushmania, so reclassification. And then in nineteen oh nine is when Brazilian doctor Adolfo Carlos Lindenberg and Italian physician Antonio Karini discovered parasites in the ulcers of those suffering from muco cutaneous lushmaniasis. Okay, okay, yeah, But despite these advancements in knowledge about the causes of these very feared diseases, there were huge gaps in knowledge that remained, and closing the gaps was necessary if there
was going to be any successful control efforts. First of all, how do people even get this disease? Understanding how a disease is transmitted is huge for identifying how you can reduce the likelihood of transmitting it makes sense. Hence masks and social.
Distancing still relevant, still relevant.
Not long after the first descriptions of Lushmania parasites, researchers thought that the disease was likely vector born, since the parasites shared some morphological similarities with other parasites that were transmitted by biting insects like tripan. So with that toge them, the search was on, and maybe surprisingly, the search went on for years, Like it took a long time.
You know.
That's interesting, Yeah.
Because the parasites themselves are easily observable, and I mean, okay, granted there are a lot of biting insects.
There are a lot of biting insects, and sandflies are very small.
They're very small, very small, I mean, but they looked into like literally everything mosquitoes, fleas, lice, midges, stable flies, ticks, tetc. Flies, houseflies, you name it.
But they maybe they didn't think about sand flies as as biting.
Anyone who's biting sand flies, you know, they're biting.
And they're the worst, the worst, the actual worst.
Horrible, horrible.
Yeah, I don't know. Maybe they just didn't think of them as vectors, yeah, because they hadn't been before.
I mean, so I think it also the conformation might have been what took so long as well, and also for a while, I think because in certain areas it might just be so prevalent, but in certain in other areas where different sandfly species maybe exists, it's not as prevalent, Like maybe it's just the association. And so for a while, bedbugs actually seemed like the likeliest culprit.
Interesting because of the housing aggregation exactly.
Yeah.
Yeah, But then a few findings steered the ship towards sandflies. First was a nineteen twelve report of flagellots found in the guts of sandflies caught at Aleppo, a place that historically has had a very high prevalence of anthropronautic cutaneous lushmaniasis.
And the second was in nineteen twenty one when two French biologists and brothers, the sergeant Brothers, Sir Jean, I don't know, Sir Jean put some ground sand flies into the skin of volunteers who then developed cutaneous lushmanias as leader.
Sorry, can you say quote unquote volunteer air quote?
I think from this point on in the podcast Long Ago, hopefully people assume air quotes around volunteers whenever it's mentioned.
It's good.
That's a good rule of thumb for this podcast. If you hear the word volunteers, just no, it doesn't really mean volunteers.
No, But this was not taken as conclusive proof the emergence of their lesions, and doubt over the life cycle of cutaneous and visceral Leushmanias as parasites lingered for almost twenty years until in nineteen forty one, five volunteers were bitten by sand flies infected with Leshmania tropica and lesions were produced. Okay, okay, there's no mention of where those volunteers came from, but there was a note saying that they all survived their infections.
Great.
A year later, sand flies were shown to also transmit visceral leshmaniasis, and the link between mucocutaneous leshmaniasis and sandflies had actually been uncovered back in nineteen twenty two. It's interesting because now we tend to think of them as
just like one, like an umbrella leshmaniasis. Yeah, I think back then it was still so divided, like, oh, well, this is another type of parasite, and so I think it the connections weren't easily made, in addition to the fact that like scientific knowledge spread a lot more slowly
back in those times. So anyway, so the second big gap in knowledge about lushmaniasis, which is effective treatment, that was filled in the nineteen forties with discovery that pentistam was effective against the parasites, and then again in the late nineteen fifties with amphoters and b and then throughout
the eighties and into the nineties. Leshmaniasis sort of took on an increased importance during the HIV pandemic, when it seemed to be highly correlated and also a cause of like you know, increased mortality among people who are already immunosuppressed and sort of like one infection feeding into the other.
But despite our long standing knowledge of these parasites and their existence, and despite the fact that we know more and have more technology to study them to develop drugs, etc. There doesn't really seem to be much improvement regarding the widespread prevalence of leshmaniasis and the absolutely enormous devastation that it causes, not just death, not just disfiguration leading to stigma, but its role in the cycle of poverty, which I'm
sure you'll talk more about. It is one of the biggest contributors to widespread travel, civil unrest, land use change,
global climate change. These have all not only perpetuated the cycle of infection and infected areas, but have also led to the emergence of different forms of leshmaniasis in areas previously unexposed, which is honestly some of the only times that it ever gets headlines in places like the US, when it's like global climate change could lead to you getting this skin eating parasite, and it's like people live with this on a daily basis, and like okay, sorry, and I love.
When your section at the end of your history section and then my EPI section are just like the same thing.
It's my favorite.
Oh my gosh, yeah, it's I mean, I feel like the history has come to just such an abrupt end because it's not over like, yeah, that's you know, where we are today is very much where we were one hundred years ago, if not in a worse situation.
Wow, that's depressing, Aaron.
Yeah, you know, we have a lot of this information, but it doesn't always reach the areas that need it. So for instance, there's you know, in the places where
there's a lot of stigma. There's also enormous problems in misconceptions regarding how the disease is transmitted, and so sometimes, for instance, it's believed in many places to be transmitted directly from direct contact, so skin to skin, and so people are often not allowed to their babies are taken away from them, or they're forced to be like, oh no, you have to go isolate for a really long time, even though that doesn't really like they are not infectious
to other individuals directly, so right, Yeah, it's honestly, this is this is one of the most frustrating diseases I think that we've covered, like, because it really does seem like why has there not been more? And people are doing a lot of work, but I just feel like this is one of the big guys. And yeah, so Aaron, gosh, Aaron, why don't you fill us in on where we stand with lushman Issis today?
Oh? I'd love to. I'll be able to answer at least some of your why why questions right after this break. Oh, gosh, Aaron. The answer as to why why? Why why? The short answer is that so lashmaniasis is considered a neglected tropical disease. We've talked about neglected tropical diseases on this podcast before, but even as far as neglected tropical diseases go, leshmaniasis
is often considered the most neglected by some people. And that's because in large part of how strong the association is between leshmaniasis and poverty, which is true for almost all neglected tropical diseases, but for lashmaniasis, it's really not enough to just say, oh, this is a disease of poverty the end, right, we have to understand the role that income and poverty play in infectious disease, and then the role like you mentioned that this disease plays in
reinforcing that cycle of poverty, and it's very multifactorial. So I'll kind of just touch on the highlights, but I do want to shout out a great paper on this topic that was by alvar at All, really great paper on this exact topic if you'd like to read more.
But basically it's very multifactorial. So in a lot of the world where leshmaniasis is endemic, people living in poverty live in housing conditions that are very suitable for sandfly growth and development, whether it's because they have cracks in the walls or damp floors or mud floors that make it very easy for sandflies to grow and live in
the domestic environment. Then on top of that, they're living with poor sanitation and maybe not often trash pick up things like that that also provide habitat for sandfly growth and development. They often live in closer proximity to animals and with a greater density of animals that can play a complicated role in the zoonotic transmission in places where this mostly a zoonotic disease, And then you have a lack of access to treatments, which can increase both anthroponotic
and zoonotic transmission, but especially anthroponotic transmission within households. So a lot of the small scale epidemiology of leshmaniasis is clustered in household groups because of.
The anthroponotic transmission. So that's how kind of the ecological.
Ways that poverty and disease can go hand in hand. Poverty also leads to malnutrition, which can absolutely and does exacerbate and worsen the symptoms and outcome of disease, especially leshmaniasis. It makes it much more likely that someone will get severely ill or die from infection rather than having an asymptomatic infection. And then on top of that displacement, whether due to war or economic necessity or like you mentioned Aaron,
climate change. Climate change can have so many effects on this disease and it will continue to do so for Yeah, yeah, there are some really interesting modeling papers that will link to to Like you said, people only care if it's in our backyard, Well that's what the modeling suggests that
it will be soon. So those things can absolutely increase the risk of disease transmission and also change its distribution so that new people who have never been exposed before are now exposed for the first time to infection, rather than having been exposed over time and developed some sort
of immunity, if that makes sense. Yes, yeah, Oh, but there's more because poverty also increases barriers to accessing healthcare, like we heard in our first hand account, whether it's leaving further from access to healthcare and having transportation barriers and getting there education barriers like you kind of touched on Aaron, such that people are either less likely to recognize disease or know how it's transmitted, or seek care
until too late in the course of disease. A lot of home remedies, especially for cutaneous leshmaniasis, result in worse outcomes compared to either just leaving cutaneous leshmaniasis alone or treating it with kind of standard treatments. And there's a lot of difficulty in paying for and receiving treatment even if you can access it, because it's expensive.
It's oh my gosh, it's enraging how expensive it is.
Yes, okay, And it's been well documented that for women, especially the stigma associated with infection and the scarring from cutaneous lashmaniasis is so severe that women are substantially less likely to seek care, so they have even longer delays in seeking treatment compared to men. In a lot of endemic areas. There has been well documentmented psychological burdens of
leshmaniasis as well. It's strongly associated with major depressive disorder, largely because of the scarring and the stigma associated with it. Let's back up a minute and talk about actual numbers for a second now that we kind of understand just how important this is in like the cycle of poverty, and that it has effects on psychosocial outcomes as well.
Right, it is, Yeah, the numbers are important because wow.
Yes, So a twenty twelve paper that's really commonly cited that has estimated because you can imagine, this is such a neglected disease that underreporting is just like we absolutely don't know the true incidence of disease. But so this twenty twelve paper that's very well cited estimated between two hundred and four hundred thousand cases of visceral leshmaniasis every year.
The one that call is death, the one.
That causes death. And here's something also important that I haven't even said yet. It's almost entirely fatal if untreated. Even if it's treated, the mortality can be as high as ten to twenty percent. So the total number of deaths per year is estimated at anywhere from twenty to forty thousand people dying from leshmaniasis.
And I wonder how many of those are also because of like not being able to afford treatment.
Exactly right, Yeah, for sure, And again that's just an estimate, like, that's our best estimate. And on top of that, another seven hundred thousand to one point two million cases of cutaneous leshmaniasis worldwide each year. So that was from twenty twelve. There are a couple of newer papers in twenty fifteen and twenty sixteen that estimate not only the incidents of infection, so the number of new cases per year, but also the prevalence of an infection, so the total number of cases.
Because again cutaneous leshmaniasis and visceral are both very long lasting disease, so someone might get infected in say twenty twenty, but still have it in twenty twenty one, or even all the way till twenty twenty two. So the prevalence of disease tells us how many people are living with
that disease currently. So the twenty sixteen estimates said that Overall, worldwide, over four point eight million people are living with leshmaniasis, and that's all forms, and that overall there were likely eight hundred thousand new cases.
Wow.
Yeah, one hundred and twenty thousand of those were likely visceral leshmaniasis and over six hundred thousand of cutaneous leshmaniasis for new cases. Now, that's just incidents and prevalence. Another thing that we have to look at for a disease like this is the disability adjusted life years okay, which in twenty sixteen overall was estimated in one year at over nine hundred and eighty thousand, So almost a million disability adjusted life years for all of leshmaniasis combined.
Oh my gosh.
But and this I think is really interesting and important.
I found a paper just from last year, twenty nineteen that suggested that we shouldn't consider having gone through cutaneous leshmaniasis and survived as no longer being affected by leshmaniasis essentially, So they suggested that the scarring phase, because we know that leshmaniasis causes these massive scars, that that scarring phase should actually be considered a part of the disease process since this is something that people are still living with
and should therefore be counted in the prevalence estimates because then based on because we also know that it's so strongly associated with things like major depressive disorder and stuff like that, so they estimated that if you include that, then we're looking at over forty million people that are living with the stigma, the psychosocial burdens and these other things that are associated with cutaneous leshmaniasis. Forty million people worldwide.
With theirst million.
Wow. So I think that that's very interesting because it really changes your disability adjusted life years if you include psychosocial disorders like major depressive disorder, which is not included in our estimates of disability adjusted life years, right, mental illness is not included in that. So geographically, leshmaniasis can be found almost worldwide pretty much, but visceral leshmaniasis ninety percent of the cases occur in a few country trees India, Bangladesh, Sudan,
South Sudan, Ethiopia, and Brazil. That's the major places where like ninety percent of visceral leshmaniasis occurs, and cutaneous leshmaniasis is most common in Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica, and Peru. So there's like a lot of places in the world, a lot of places, a lot of a lot of places, and the distribution is likely changing due to climate change. Okay, I want to say it's not all depressing, but it's mostly all depressing.
But there are a lot of people doing a lot of work to try and make this better.
Yes, that is important to remember.
Yeah, we've talked a lot about Peter Hotez on this podcast.
Oh yeah, peteryot He is one one of many people really doing so much work on vaccine development and really just I think bringing awareness to diseases like leshmaniasis as well.
So in terms of where we stand on a vaccine, it's still not great news. There is a lot of good evidence to suggest that, at least from the perspective of people being able to theoretically mount a protective immune response,
that we should be able to develop a vaccine. And actually, people like even in ancient times, have practiced leshmanization right, which is basically inoculation of parasites under the skin to like intentionally induce an infection not on your face but on your body to then protect you from more worse and disfiguring infection later on, and that's like effective, but of course it does result in infection, which is not good.
And it's not perfect either, and so the big stumbling blocks to the creation of a vaccine are both financial and also logistical. We don't have a perfect vaccine. There are a few different vaccines that are being tested right now in phase one and phase two trials. There are recombinant vaccines, so like just a protein that we know would cause an immune response, along with different adjuvants to increase the immune response. There are also killed parasite vaccines
that are under investigation. There's talk about DNA vaccines, but I don't know that any of those are in kind of later stages of development, so it'll be interesting to see how those go on. As well as therapeutic vaccines, so vaccines that you give to someone who has like cutaneous leshmaniasis to prevent the development of mucocutaneous leshmaniasis, etc. Dogs, As it turns out for zoonautic leshmaniasis are a pretty
important reservoir host. So there are a couple of K nine vaccine that have shown some promise in preventing dogs from becoming infected, which may be useful in some areas, but it probably won't have like the full impact that we need, especially because a lot of regions with visceral leshmaniasis especially have mostly anthroponotic transmission, so dogs don't play as big of a role in that. I mean, they don't play a role at all. So yeah, so that's
where we stand. There's a lot of people working on it. There's a lack of funding, even though it's been shown, like in a lot of different modeling studies, to be very cost effective, Like the cost to develop and implement a vaccination program would be way cheaper than treating people for visceral ancutaneous lash meniasis.
Yeah, but there's no money in it. If you vaccinated someone against a disease, then you're not going to be able to get the year you know, the month's supply.
Of but you get so many disability adjusted life your life. Isn't that what people want? You can then work anyways.
I know there's a lot of problems with like why certain things are funded and others are not.
Yes, so you know, Hoody Hot also Maria Elena Potazzi, who we talk to in one of our COVID episodes. She's on a couple of these papers too. She's doing a lot of work on this. There's a lot of other people. I probably should shout them all out, but those are the two we've talked to. So I feel cool.
Well, I think it's I mean, I think it's really amazing and important because like this, this research isn't easy to do because the funding just like isn't it isn't sufficient, It isn't. Yeah, but it's hugely important and so.
It is hugely important. Yeah, so that's where we stand erin. Oh boy, well I learned a lot.
I learned a lot. It's a big disease, and I really feel like I didn't do the history justice. But I also feel like there's just like I couldn't find as much as I normally can find on stuff like this. And so someone needs to write a book about about this.
You write erin, someone needs to write a book. Guys, let us know if you would like to read a book that Aaron Welsh writes about lashmaniasis, or if you'd prefer a different topic. Let us know what do you want her first book to be about?
Volunteering me to do a lot of work eron. Okay, yes, I want to read it, appreciate speaking of books and things. Should we disource it?
We should?
So I have a bunch of different articles, but I want to shout out a few. So one that I found super helpful for the overview of the history is by stever Ding from twenty seventeen called the History of Lashmaniasis. And then there are a few different papers about the origin of Lashmania and the sandflies. And so there's one by Moment and Koupolilo from two thousand called Speculations on
the Origin and of the genus Lashmania. There's a paper by Killick Kendrick from twenty thirteen, the Race to discover the insect vector of kala Azar. And then there's a paper by Guran from twenty eighteen called an overview of Leshmanias's historic to future Perspectives. And there are many more. All post them all.
I already shouted out a few of the papers that I read. There's a lot. We post the full references to this episode and all of our episodes, every source we've ever used on our website This podcast will kill You dot com, So check them out there under the episodes tab.
Yeah. Well, Thank you to Bloodmobile for providing the music for this episode and every single one of our episodes.
All sixty two now episodes.
Not including the covid ones. Yeah yeah a lot.
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