This Podcast Will Kill You - Ep 78 Bartonella: Keep Calm and Carrión

Episode Date: July 27, 2021

“Let’s do Bartonella next,” we said. “It’ll be straightforward and fun,” we promised ourselves. Turns out we were half right. In this fun but not quite straightforward episode, we tackle not one, not two, but three different species of Bartonella bacteria that can cause disease in humans: Bartonella bacilliformis (Carrión’s disease), B. quintana (trench fever), B. henselae (cat scratch disease). Essentially, we’re giving you three mini-turned-maxisodes for the price of one! For each pathogen, we review its surprisingly strange biology, take a brief tour of its history, and wrap up with a look at its current status across the globe, comparing and contrasting along the way. By the end of this ride, you’ll be bursting with Bartonella trivia, in awe of dental pulp, and scratching your head about the transmission of cat scratch fever. See omnystudio.com/listener for privacy information.

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We tossed down for the night in the hopes of getting some sleep, but it was not to be. We no sooner lay down than hordes of lice got up. So we went round to the medical officer, who was also in the duckout with his equipment, and he gave us some ointment, which he assured us would keep the little brutes away. We anointed ourselves all over with the stuff and again lay down in great hopes, but it was not to be, because instead of discouraging them, it seemed to act like a kind of hors d'oeuvre, and the little beggars went at their feast with renewed vigor. A full day's rest allowed us to clean up a bit, and to launch a full-scale attack on lice. I sat in a quiet corner of a barn for two hours delapsing myself

as best I could. We were all at it, for none of us escaped their vile attentions. The things lay in the seams of trousers and the deep furrows of long, thick woolly pants and seemed impregnable in their deep entrenchments. A lighted candle applied where they were thickest made them pop. After a session of this, my face would be covered with small blood spots from extra big fellows, which had popped too vigorously. Lice hunting was called chatting. In parcels from home, it was usual to receive a tin

of supposedly death-dealing powder or pomade, but the lice thrived on the stuff. We had to sleep fully dressed. Of course, this was very uncomfortable with the pressure of ammunition on one's chest restricted breathing. Furthermore, when a little warmth was obtained, the vermin used to get busy.

And for some unexplained reason, they always seemed to get lively in the portion of one's back that lay underneath the belt and was the most inaccessible spot. The only way to obtain relief was to get out of the duckout, put a rifle barrel between the belt and rub up and down like a donkey at a gatepost. This stopped it for a bit, but as soon as one got back into the dugout and was getting reasonably warm, so would the little brutes get going again. That's really funny. So those were all accounts of lice during trench warfare during World War I.

It sounds truly awful, Aaron. I just can't imagine. And I also have some numbers that I'll share later on just to kind of like put an even more horrific spin to this. Yeah. Lice flees, all the little things that just don't stop biting you. I know. I know. Yeah.

By the way, those were from various soldiers from World War I, and we will post the full, like, names and links and whatever on our website. And also, hi, I'm Aaron Welsh. And I'm Aaron Allman Updike. And this is, this podcast will kill you. And welcome to a very weird episode today. Yeah. We did not intend for this episode to be, we had no idea what we were. we were getting into. We thought this was going to be a run-of-the-mill episode. Yeah. And it's not,

but that's okay. We were very wrong, but we, that means we learned something new. Yeah, lots, lots of new things. Yeah. So what are we covering today, Erin? Well, it's a good question. We're covering the genus Bartonella, which causes a whole bunch of diseases, some of which listeners you may have heard of, like cat scratch disease, for example, also trench fever, hence the lice in trenches, first-hand accounts, and also Carillon's disease. Yeah. Which you may not have heard of, because I hadn't really. I hadn't either, but I learned a lot about it. And I think it's actually going to be fun to do. I'm excited about it. I think it's going to be, at least, I don't know, something new. Yeah, yeah. And so,

This episode is going to be formatted a little bit differently. Just as an explanation, what we're going to do is we'll go through the biology history, biology history, biology history, in sort of like three mini episodes, almost. And then we'll wrap it up with the current status. And that's kind of how it'll be. It's like three episodes for the price of one. Yeah. Yeah. Look at it that way.

Certainly the work felt like three episodes for the price of one. Yep. 100%. So speaking of which, I think it's about quarantine time. It is. What are we drinking this week? We're drinking a game of cat and louse. I love this name.

I also do too, even though the cat scratches really flees more than lice, but it's still really good. Yeah. What's in a game of cat and louse, Aaron? In a game of cat and louse is gin, peach nectar, sparkling water, and, and, and some lemon juice and then garnish it with a little fresh sprig of rosemary. Yum. Yeah. And we'll post the full recipe for that quarantini as well as our non-alcoholic placebo

Rita on our website, this podcast will kill you.com and on all of our social media channels, as always. As always. And business. Our website, you can find lots of things. You can find transcripts. You can find our references to all of the episodes. You can find a goodreads list, a bookshop.org affiliate account, a link to all of our, like, promo

codes that we talk about in the ads, Patreon. I mean, I'm probably missing many things, merch. But if I've missed it, just go to our website and you'll be able to find it there. It's true. There's a lot there. Yeah. All right. Should we get started on this very unusual episode?

Yeah, I'm excited about it. Let's take a break and then dive into the first of three minisodes. Yeah. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients so there's no meal planning and no extra grocery trip. There, assemble and bake meals take about five minutes of hands-on prep.

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So just up front, what I'm going to do in this biology section is kind of go over the genus and all of the general things that we know about the genus Bartonella and the many species of bacteria that cause disease in humans and other animals. And just sort of go over the similarities and then focus on one specific species, and that is Bartonella bacilliformis. and that's Aaron what you're going to then cover, etc., etc. Okay. And what makes this even more confusing is that even though we're going to focus on three specific bacterial species, there's like five or six or maybe seven, depending on how you count them, different diseases that they cause. Yeah.

And there are some species that are not human-specific or like not commonly human pathogens, but do infect humans, but we're not going to go into those. Yep. So let's talk about them all in general, shall we? Yes. So in general, the genus Bartonella are small, fastidious, which we know means difficult to grow in culture. I love that word.

I know. It's such a good word. Gram-negative rod-shaped bacteria. There are dozens of species. Over 30 that we've identified. so far. But again, we're going to focus on three today, but know that there are others that can cause some of these same diseases, and there's probably more that we just don't know about yet. And I think that, Erin, you're going to talk a little bit more about the overarching evolutionary

history. But it does seem that there are a lot of species that are relatively specific to certain mammals. Like there are some species mostly found in rats and others mostly found in cows or cats, etc. Mm-hmm. Yeah. And there's two species that will focus on today that are specific to humans, and then another species that commonly infects humans, even though it's a feline species. Simple.

Simple. No problem. No one's confused yet. In general, these bacteria are transmitted to these mammalian, usually mammalian hosts, by blood-feeding arthropod vectors. But of course, they're not simple. So it's not like just one type. Sometimes it's sandflies.

Sometimes it's lice. Sometimes it's fleas. Maybe it could even be ticks, some people are saying. Oh, goodness. And if anyone listening has heard of cat scratch disease, you might already be scratching your head, scratching. Like, I'm sorry, I thought that cat scratch disease was from cat scratches. And we'll get there. People will get there.

but for the most part these are vector-borne pathogens but to make it even more confusing unlike many vector-borne pathogens that we've covered on this podcast that are picked up in the bloodstream and then spit out in their next blood meal to infect another host these ones are sometimes transmitted that way like when it's sandflies but sometimes they are picked up in a blood meal and then replicate in the guts and then are pooped onto the mammal and then have to be scratched into a bite wound. So these are complicated bacteria. And then once they get inside their mammalian host to be even more complex, Bartonella exists as intracellular bacteria. So they don't just live inside us and replicate like, say, staff or strep or many other bacterial species, but they're more like legionella that we just talked about, or chlamydia, gonorrhea, etc.

Rickettsia. Riketia. They go inside of our cells and replicate the way that viruses do. In mammals, not in the arthropod vector. It's kind of impressive. I know. It's very cool. They're facultatively intracellular.

It's very, very awesome. So that was all the really complex part. Let's talk about what they all have in common once they're in mammalian hosts. Because it's actually kind of simple and tells us a lot about the diseases that they tend to cause. So in mammals, Bartonella tend to infect two different cell types, two different kind of tissue types. red blood cells, erythrocytes, and endothelial cells, which are the cells that line our blood vessels and can also be found in places like lymph nodes. They can also infect white blood cells. And those two cell types, infecting and causing damage to those two cell types, actually explains a lot

of what we see in terms of the actual symptoms of disease. Right. So at least that's one thing that they tend to have in common. Asterisk cat scratch disease is weird. Okay. All right. So that was all of the general details. Let's focus now on one species, Bartonella bacilliformis.

Listeners, you may have never heard of this because I had never even heard of it. This is a particular species that is human-specific, so it doesn't infect as far as we can tell, other mammals, at least not naturally. and it causes a disease known as Carion's disease. My accent is probably terrible on that. But also sometimes Carion's disease is called two different diseases because this is a biphasic illness. So there's an acute stage and then a potential chronic stage and these two phases are completely different.

That is fascinating and I don't understand it. And I kept confusing the two phases and yeah. Well, hopefully when I explain it, the two phases will make at least a little bit more sense. Okay. So this particular species is vectored by sandflies in the same genus that we talked about with Leshmaniasis of all things, Lutsomia sandflies. Yep. And part of the reason that many listeners may have never heard of it is that it's very

geographically limited to certain parts of the Andean valleys in South America. So Peru, Ecuador, and Colombia, and only parts of those countries. It's like a really narrow altitudinal range, right? Yes. And it's where this particular sandfly species is found. Yeah. Yeah. So let's go over the symptoms of this one disease, Carriands disease, which is sometimes called two different diseases. In the acute stage, which happens the first time that somebody gets infected. And the symptoms start usually about 60 days after infection. So it's a really long incubation period. Whoa, I did not know it was so long.

Yeah. And some estimates that I saw ranged from 10 to 200 days. And I wonder how much of that variability just has to do with how little we really know about this disease quite honestly. Yeah, this was like this was the one that was the most difficult to get information on, I think. Absolutely. So the acute stage of Carion's disease is sometimes called Oroia fever. Mm-hmm. What it looks like is a headache, some general feeling cruddy like malaise, maybe some joint pain, bone pain, and that will progress to chills and a fever. But then over the course of one to four weeks, this becomes much, much worse. People infected become pale, jaundiced. They might have difficulty breathing. They might become confused. And this can progress to

multi-organ failure and death. And some reports say that the mortality rate is anywhere from 40 to 88% if untreated. Yeah. Which blew me away. Yeah, same. And I'm going to talk about it in a little bit more detail in a second. But first I want to talk about what's happening in this acute phase of the disease, because it goes back to what we already know about this genus of bacteria. What's happening in this acute phase is that these bacteria are multiplying inside of our red blood cells. We know that that's one of the cells they like to infect. But in the case of this particular species, Bartonella bacilliformis, these bacteria replicate rapidly and enormously into like huge numbers. And then they end up bursting open those red blood cells.

So this can cause a severe hemolytic anemia. That combined with secondary bacterial infection is what often causes death. Why is there secondary bacterial infection? I'm not entirely clear, but likely. It's just how overwhelmed the immune system is already makes you more susceptible to secondary infection. You have an overwhelming bacteremia. So so much bacteria in your blood already, your immune system's probably just not able to

fight off other organisms. And so in that very wide incubation period, once symptoms do start to appear, what sort of the timeline there? From what I could gather, a number of weeks. So one to four weeks is when these symptoms sort of sort of start. start and then progress. Okay. But I want to get into it a little bit more because there's actually some evidence from some more recent outbreaks that have happened in non-endemic areas that the mortality rate might actually be a lot lower, not just because of good treatment, which can certainly

help, but it's likely the case that there's actually a lot more sub-acute or sub-clinical, like not symptoms or barely any symptoms where people get infected, but they don't even really know that they're sick, that happens that we didn't know about when it was just the people coming in really, really sick and then dying. Does that make sense? Yeah, no, I saw that also. And it made me wonder, why does that happen? Like, why are there certain people? Because, like, from the history section, it doesn't seem to be, like, people who are already, like, immunocompromise. It doesn't seem to be like people who are in advanced age that are more likely to die. It just seems sort of random almost. Right. Yeah. I honestly don't know. This was a disease

that was really difficult to get like super clear information on, likely because it is pretty rare. And then those non-indemic areas, that is where it like might be a different species of sandfly or potentially different species of sandfly, which could mean like a variant of the pathogen itself. So who really knows, quite honestly? Yeah. But in those outbreaks, though, what they found is that over 75% of a population had antibodies. So lots of people were getting infected, but only about 14% had symptoms of Oroia fever, this initial infection. And then about 17% went on to develop the chronic form. And what's even more interesting is that only 5% had this bifasic illness where they first had a oroia fever, and then they went on to develop chronic form.

But a lot of people had the chronic form, quote unquote chronic, without ever having symptoms of arroya fever. Okay. That is very interesting. So one of the questions that came up while I was reading was that, you know, it seems that this is human specific. And so that means that there would be no reservoir animal that we've, found yet. And so are people just like reinfecting the flies forever? Like how has this not burned through unless it is this high rate of subclinical cases that lead to just persistent like pathogen presence? Exactly. And honestly, that that probably is what it is based on how Bartonella exists in so many other reservoir species. Right. It's very common to have a chronic bloodstream infection that kind of you'll have a lot of bacteria in the bloodstream and then, you know,

the numbers will decrease and it'll sort of cycle like that even without having any symptoms. Yeah. So, but speaking of symptoms, the chronic, quote unquote chronic disorder that you can get, which can happen, I didn't get a timeline on how long after initial infection this tends to happen. but what can happen over a course of time is a disorder known as Viruga Peruana. And this is a cutaneous, so a skin disease. And you get these little vascular tumors, really, these little lumps or bumps or nodules.

They look like little red or sometimes purple, almost black, raised moles. like not quite wardy looking, but almost like a very red or purple lumpy lump just stuck onto your skin. Right. Yeah. And they can actually have quite a lot of different appearances. Sometimes that's what they look like and they're little and tiny, like less than three millimeters and just all over your body, especially on your arms and legs. Sometimes they can be a bit larger or even have like multiple little nubbins all in one. Or sometimes it can manifest with deeper, kind of suburb. dermal nodules. And when those are present near a bone, like say right on top of your shin, for example, those can be kind of painful. But the reason that these are red to purple,

to dark black in color is because they're actually derived from vascular tissue. So these little lesions are made from blood vessels that proliferate. That's wild. Uh-huh. But it's not that wild when you know that this bacteria infects the lining of our blood vessels. So it's basically just the bacteria causing proliferation of blood vessels in which it lives. That is ridiculous. Uh-huh. Wow. I know. And so these continue to develop often over the course of three to six months. You can imagine that because these are literally like made from blood vessels, it's very easy if you scratch them for them to open and bleed pretty profusely more than like a normal mole would bleed if you scratched it, especially on the arms and legs. But in general, they tend to heal

on their own even without antibiotic treatment. Huh. Okay. Yeah, it's a very interesting, and I think that a large part of the reason that they are able to heal on their own is because, in general, with this disorder, Veruga-Peruaguana, or the chronic form of Carion's disease, these nodules tend to be limited to the skin and maybe a little bit deeper into like the subcutaneous tissue or maybe rarely the muscle. But they don't go any deeper than that. That's important for a different disease that we'll talk about later. Okay. Was that enough? That was a lot, Erin. No, I feel like this is going to be instead of three mini-sodes, this is going to be three full maxi-sies. full maxisos.

But so that kind of sums up the genus that is Bartonella and then Bartonella basiloformis in specific. I think that that particular species is a good example of not only how severe this disease can get, but also why it's able to cause the diseases that it causes. Right. And we'll go over the other two species that most commonly cause disease in humans later. But Aaron, first off, can you walk us through the history of this? disease. I can, and we don't even have to take a break first. Yes. So like you, Aaron, I wanted to start out with a general overview of the group of bacteria that we're talking about today, because even

though the human histories of each of the three species we're talking about are very distinct from one another, being in the same genus, of course, means that they share an evolutionary history. And it turns out that evolutionary history is actually pretty interesting. Of course. So the genus Spartanella is a fairly, like you mentioned, diverse group of bacteria that tends to, though not always, show high host specificity for its mammalian host or arthropod vector. And side note, it wasn't always known to be diverse. until 1993, the genus consisted, I think, of just Bartonella Bacilliformis. Yeah, which is so fascinating to me.

I didn't realize how recent it was that we even knew that like cat scratch fever or cat scratch disease and trench fever were caused by bacteria in the same genus. Like, it's super recent. Yeah, it is really recent. And part of that recency, like, we knew about some of those pathogens before, but this was just like merging with another genus. And so it was sort of just like this restructuring of naming and grouping, and it does make looking at old papers more difficult and whatever, but it makes sense. And so here they all are together. Yeah. So anyway, even though we're only focusing on a few Bartonella species,

there are a whole lot more where those came from, with Bartonella species infecting many other mammal species. But they didn't start out that way. This group, the Bartonella ACA, is nested within the rhizobials, which is a group of nitrogen-fixing soil bacteria. Oh, fun. Yeah. And so researchers think that Bartonella probably started out as an environmental pathogen, and Bartonella bacteria are closely related to some plant pathogens and symbionts, and then that environmental pathogen turned into an insect gut symbiont, which then turned into a vertebrate pathogen.

Oh, my goodness. Yeah. And this last transition from insect gut symbiont to vertebrate pathogen is believed to have happened around the Cretaceous paleogene boundary, previously known as the KT boundary, which is about 66 million years ago. So like, you know, when all the dinosaurs died in the big extinction event. And also around the time, when there was like a big beginnings of mammal diversification as well. Right, right. Okay. And so what might have happened is that these arthropods that were hosting Bartonella

began to evolve to be able to feed on the blood of these mammals, and then the Bartonella species inside them began to evolve to be able to infect those blood feeding arthropods, and then through that, the blood of mammals. I love this so much, Erin. I had no idea. I know. It is so cool. It is so cool. And so then after that, it was like, all right, let's, I found my vector, I found my mammal, I'm good to go. Let's just follow this evolutionary train right down the line. Yeah. And so that's when like a lot of these fairly tight vector host pathogen relationships began to form. Oh my gosh. That is so cool, Aaron. Yeah. I really like that. There was a recent paper looking at the patterns of diversity.

within Bartonella that suggested that bats were among the first mammals to be infected, and that both bats and rodents were key in Bartonella both diversifying and spreading like millions of years ago. And then more recently, though, in terms of evolutionary history, there was another paper that talks about the role that humans have had in this recent spread of Bartonella species through the movement of domestic or human-associated animals. So like dogs, cats, cows, rats, etc. And that's fairly unsurprising. But what is cool is that we've seen not necessarily like, we've seen some spillover events

and we've seen kind of like these not quite host switching events, but more like Bartonella species that are fairly host specific being able to infect other mammals that occupy the same ecological niche or geographic area. You mean like cats and people? Exactly. Oh, okay. But Bartonella, I think, is a cool group of bacteria because in addition to telling us how different animals migrated and spread geographically, it's very long history and broad host and vector

diversity. It makes it a great group to study things like vector host pathogen co-evolution or the evolution of host specificity, or especially something that I was thinking a lot about during this episode, was the trade-offs between being a generalist pathogen and one that is specialist. Yeah, yeah. Because if you're a species of pathogenic bacteria, it may seem like on the surface that, you know, if someone gave you the choice, do you want to be able to infect as many host species as possible, or do you want to just put all of your eggs in one basket, you would probably

be like, eh, I think, you know, I'm going to diversify here. That's going to be the best way to go. But that's not necessarily the case. We all know, like, in life, you can't make everyone happy. And along those same lines, you can't infect everyone successfully either. Because being well adapted to one species may make you more visible to the immune system of another. And there's a lot of other like tradeoffs that you can go into in terms of specificity versus generalist. Right. And I've also seen it predicted like overall that single host pathogens will be more successful than multi-host pathogens.

But it's also not necessarily as clear cut as that, especially in light of like widespread land use change and climate change. Like having the ability to exist in multiple different species might make you a little bit more resilient to change, for instance. But anyway. And so this is why these tradeoffs and the fact that there isn't a clear answer is why we do see some pathogens putting all their eggs in one host, and others are spreading their eggs across many hosts. Literally and figuratively. Yeah. And so the same goes for Bartonella, right? You'll find ones that are generalist, especially those whose vector species tend to be more generalist biters as well. Like many of the roeastern.

end ectoparasites, and some that are very host-specific, infecting only one mammal species, or just ones that are closely related. Which brings me to Bartonella Bacilliformis. This Bartonella species, despite being the deadliest in humans by far, and the first one to be described in general, not just on this podcast, but in history, actually has quite a small history. And that kind of makes sense based on what you said. It's very localized.

It's fairly, like, rare occurrence-wise. And, yeah. And so let's go into the biggest outbreak that we know about to date. Okay. In the 1870s, construction on a railway linking Lima and La Arroya began. Mm-hmm. And a good number of the laborers that were working on the lines weren't actually from the area. they had come in from elsewhere.

And they, during this construction, began dying by the thousands. Whoa. Absolutely astonishing numbers. It was estimated that more than 7,000 of the 10,000 workers building this railroad died of this unknown disease. Okay, that's just a straight up mortality rate of 70%. Yeah. Yeah. So that's, I just was blown away.

I was like, wait a minute, are you sure? Are you sure? Yeah. Oh, my goodness. Yeah. And so like you said, this disease sort of took this typical course or I guess it's not so typical now that I've heard the biology, but of first this febrile, hemolytic anemia, which was often the fatal part of it. And then if they survived, skin nodules. But it turns out that this unknown disease wasn't quite as unknown as people thought. Later, you know, looking back in history, showed that there was some pottery from ancient Peru, like 2,000 years old, that seems to depict some of the symptoms that the workers were having, like the skin nodules. And it was also probably described in some of the journals written during the Spanish invasion of South America. Oh. But this large outbreak, which gave rise to the name Oroya Fever, brought a lot of attention to the disease. and in 1885, a Peruvian medical student named Danielle Carillon gave it its other name Carillon's disease. When he inoculated himself, I see you frowning already, you know what happens. I know. I usually am so good, but it was like in the front of every paper.

Every paper, yeah. I know. That's just how it is. Yeah. Well, we'll share with the group. Danielle Carillon inoculated himself with some, I put juice from an infected skin lesion. I don't know if it was blood or pus or what juice, something from someone who had that second phase of the disease and then he died of this febrile anemia, so like the first phase.

His death through this very tragic experiment also showed that the two diseases were linked. and likely caused by the same thing, which up until that point had not been known for sure. Okay. And then in 1909, Alberto Bartone, hence Bartonella, Bartone. Yeah. A physician from Peru published a paper describing bacteria in the blood cells of people with Aroya fever. But this on its own apparently wasn't good enough. This I found bacteria in the blood cells of people who had this disease and also,

Danielle Carillon dying. That wasn't good enough. And so a group of researchers from Harvard University went down in 1913 to conduct some experiments involving human, quote, volunteers. Oh. Uh-huh. In which they basically repeated Carri-on's fatal experiment. Only the person didn't die.

And so the researchers were like, eh, I mean, are they really related then? Like, are these really the same disease? Oh my. Yeah. And so eventually, however, it was accepted that both Arroya fever and Carrione's disease or Veruga were caused by the same bacterial species. Still, though, many questions remain like we talked about, right? We have no non-human vertebrate reservoir. It historically was thought to be really restricted to just that, like, Verrui.

zone, but as you mentioned, there have been outbreaks, like sporadic outbreaks of cases outside of that zone. So, like, is it a new species? Are there new strains, et cetera? We're going to need some updates on this if you have any, but... We'll see, Aaron. Well, for now, let's just head to the next on the list. Okay. Oh, that was a good history, Aaron. Oh, thanks. I really truly had had no clue what we were getting into. I know, I know. We'll take a quick break before we get into the next one. I think that's a good plan.

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Not compatible with any other offers. Zero percent APR financing for 60 months equals 1667 per month per 1,000 financed for well-qualified buyers through Stalantus financial services regardless of down payment. Not all customers will qualify. Contact dealer for details. Offer ends 3-2. So our second species of Bartonella of the day is Bartonella Quintana.

And this causes the disease that many more people have probably heard of, and that is trench fever. So this particular species is transmitted not by sandflies, but by the human body louse. Piticulus, humanis corporis. You like that? I do. I love, I mean, I don't love body lice, but I find lice to be really truly fascinating. Talk about species specific. There's a body louse and a head louse, and they are different.

I was, I did not know that until this episode. Yeah, uh-huh. So this is transmitted by the body louse, not the head louse, so don't freak out when your kid brings home lice. they're different. Although it can be transmitted through headlines. Yeah, it probably can. It can be. But it's rare.

That's not what usually happens. Oh, but like with Bartonella bacilliformis, there is no known natural animal reservoir for Bartonella Quintana. So as far as we can tell, this is a human-specific disease, which makes sense if it's being transmitted by the human body louse. And like Oroia fever, the acupun, the acupun, stage of Karyon's disease. Trench fever is a bloodstream infection. So this is a disease that happens when these bacteria replicate and proliferate inside of our red blood cells. The symptoms,

though, look a little bit different. The symptoms are a periodic relapsing fever most often. And this can range from fairly mild to pretty severe in terms of symptoms. But in general, the onset is sudden and starts about a week after infection, although the incubation period can be up to 25 days, and starts with a fever that tends to last classically five days, but I saw some papers that said like one to three days. So everything in medicine that's called classic is probably not 100% true. I'm going to make someone angry, but that's the case. But this fever is associated with severe headache, often dizziness, and for some reason that Aaron do not ask me why, shin pain. Okay, so I do have a question about shins, though.

Okay, Aaron, what's your question? That is in the quote-unquote classic description of the disease, which, you know, spoilers was first described in World War I. And so I was wondering if it was something about the conditions of the trenches or, you know, what it was like to be in the trenches. Do people who have trench fever today still describe severe shin pain? Good question. That's a very good question. In most of the descriptions that I read, they likely go off of some of those more classic descriptions rather than, I didn't read a lot of individual case reports to know what specific people's symptoms were today. But other papers that I read said more generally bone pain. And joint pain is also really common, which makes sense because

you have blood cells, that's where your blood cells are coming from. So it does make sense that there would be bone pain, but maybe it's not always specific to your shins. And maybe in World War I, it was something to do with that rather than specifically just this. Yeah. Okay. Interesting. Good question. So in general, this is a disease where these fever episodes often recur. And when they recur, it might be every four to six days or so. And so because some people say the fever last five days, or sometimes these episodes recur every five-ish days, trench fever is often sometimes called five-day fever or quinton fever. Right. Side note, you know what's interesting, Aaron, trench fever, recurrent febrile illness where bacteria is infecting your red blood cells.

Malaria, recurrent febrile illness, where. where parasites are infecting your red blood cells. Yeah. Yeah. And only, so this is what, that's what they noticed during World War I, and they tried to treat them with quinine, but. That didn't work. To no avail.

Yeah. I just thought that was an interesting little side note. Which also brings me to another question. Okay. Why is it relapsing? It's a really good question. There's a number of, there's another disease that is louseborne relapsing fever that's caused by a different species of bacteria.

It's a Borrelia species. Right. I'm not entirely sure why. And this comes back to the fact that we don't have good animal models for these illnesses. So the specifics of a lot of this pathophysiology, I just don't have answers to. Huh. Yeah. But unlike Bartonella bacilliformis, the cause of Carion's disease, trench fever, Bartonella Quintana, does not cause a severe.

hemolytic anemia. So it's generally self-limited doesn't have a huge mortality rate. Certainly people have died from it, but it can also cause a chronic infection, like we've seen with bacilliformis. It can also cause an asymptomatic infection entirely. And it can go on to cause some pretty severe infections, much more severe than trench fever. So there's a whole other disease called bacilliary angiomatosis. Uh-huh. Yeah. Baciliary just refers to involving a rod-shaped bacterium, so that's the bacterium in this case. And an angioma is an abnormal growth either on the skin or internal organs that is due to the formation of new blood vessels or the dilation of existing ones. Does that sound familiar? Uh-huh. It certainly does. Yeah. So basiliary angiomers,

was discovered in HIV positive patients. So primarily it's a disease of immunocompromise. And it has been found to be caused often by Bartonella Quintana and other species of Bartonella. Uh-huh. Oh, yeah. I'll get to you a little bit more later. So what is it exactly? What does it look like? It's lesions not so dissimilar to Varuga-Peruana.

but dissimilar enough that baciliary angiomatosis is a very severe illness. These lesions are most often and most obviously on the skin, but unlike with Viruga-Peruana, they're not limited to the skin. The damaging part is that these same lesions, these like tumors made from blood vessels essentially, can be found on any other internal organs. And you can imagine these are blood vessels. they can bleed quite intensely. And so that bleeding itself can be life-threatening,

as well as just having these growths that can get large on other internal organs. So bacilliary angiomatosis is a much more severe disease that can also be fatal. How often does that occur? I guess like if you are immunocompromised, how often does it occur? It's a good question. I don't have solid numbers on it. The numbers that I saw in people living with HIV, the prevalence of Bartonella associated infection is still quite low, like one in a thousand in some studies in Germany and Spain.

Okay. Yeah. So it's still a very, very rare disease. It's not only associated with HIV. It also has been found in people who are organ transplant recipients and other cases of immunocompromise. In rare cases, it has happened as well in people who are otherwise immunocompetent. Why? Great question, right?

Yeah. We don't know. And then finally, because that's not quite all, Bartonella Quintana has also come very recently within the last couple of decades to be recognized as an important cause of what used to be called culture negative endocarditis. Endocarditis we've talked about a lot. This is an infection of the heart tissue itself, which again, unsurprising, considering this bacteria likes our endothelial cells. And so endocarditis associated with Bartonella, as well as

trench fever, have both become important causes of disease today, not just in world wars, but today among people experiencing homelessness. And so that's the majority of where we see Bartonella Quintana infections today. I actually have a bit of trivia, too, about endocarditis that I didn't include in like my little history section. Oh, tell me it. So during World War I, there was a condition that was called either disorderly action of the heart or soldier's heart, which was a variety of like shell shock. Like it was just sort of this, no one knew what was causing it. And one paper I read suggested that at least some of these cases might have been caused by this endocarditis caused by Quintana. Fascinating. Oh, that's really interesting.

Yeah. Erin, tell me more interesting things. What's up with this particular species of Bartonella? Where did trench fever come from? I'll get right into it. Okay. This is fun. Yeah, I'm really learning a lot. Yeah. Okay. On July 28th, 1914, World War I began. And this episode, I looked it up, I'm pretty sure, will actually be released on July 26th. And so that'll be the day before the 107th anniversary of the start of the Great War. Wow. Yeah. Timely. Totally planned. Yeah, sure. By September of 1914, trench warfare had begun on the Western Front, starting with a battle in France.

And when I say trench warfare had begun, I mean it had begun. Within a few months of this battle, 4,000 miles of trenches were dug and maintained from the English Channel to Switzerland. Whoa! Trench warfare was brutal, it was deadly, it was horrific, and in these trenches, soldiers would live, they would fight, they would die, and many of them would get infected with trench fever. By June 1915, an unusual febrile infection was running rampant through the troops that spent a lot of the time in the trenches, and it drew enough attention to end up in a report by British medical officer Major John Graham. Quote, a private from an infantry regiment was admitted to a casualty clearing station suffering from a febrile illness of three days duration. headache, dizziness, severe lumbago, a feeling of stiffness down the front of the thighs, and severe pains in the legs referred chiefly to the shins.

I have been receiving cases in considerable numbers presenting clinical features which do not differ from those given above. And this was the first description of what would become known as trench fever, an illness that didn't often kill you, like rarely killed you, but it would take a lot of out of you, leaving you as a soldier unable to fight for up to two months at a time. Wow. That's a long time. It is a long time, yeah. After this first report, military physicians all over began recognizing it in the troops that they treated. And after first being seen in British soldiers, it popped up in French troops, then in Greece, Italy, and all across the Eastern Front. And it wasn't

just limited, of course, to the Allied forces, regardless of where you were from or who you were fighting for, if you found yourself in the trenches, you were likely to find yourself with trench fever at some point, or at least the person standing next to you or digging the trench next to you was likely to have trench fever. And while some soldiers viewed trench fever as a welcome relief, because it took you off the front lines for like 60 to 70 days to recover, and actually, one paper pointed out that it probably saved a lot of lives that way. Yeah, that makes sense. Yeah. Those higher up in the armed forces sought as a massive problem in reducing the sheer numbers of available troops. This was like a lot of this was just a numbers game. And it certainly

did reduce these numbers. Official records were not kept on the overall incidence of the disease, but I did see one estimate of about one million cases among the allied troops alone, which is quite a lot. There were actually a lot of famous people with trench fever. Oh, I feel like we haven't done famous people with this disease in a while. We really haven't. And this, there's a really funny, these are all, I'm sure there are more that are out there. But I just came across an article that mentioned the names A.A. Milne. so Winnie the Pooh.

Oh. Okay. J.R.R. Tolkien. Oh. Uh-huh. And C.S. Lewis. Oh, wow. All got trench fever.

I think Milne was actually taken off of the lines entirely because of trench fever. Oh, my gosh. And, yeah. We can probably think trench fever for Winnie the Pooh. And Lord of the Rings. And Lord of the Rings. And the Line, the Witch and the Wardrobe. We know things.

Yeah. Trench fever caused one-fifth to one-third of all illnesses in the British Army and one-fifth in the central powers. Wow. This is a lot. And even once the war was over and the disease had run its long course, many people were still impacted by it. For instance, 6,000 men in Britain attributed their war disability to trench fever in 1920. So a couple years after the war ended. And while trench fever could not hold a candle to the morbidity and mortality caused by influenza or typhoid or cholera or dysentery or all of the other diseases that were flourishing under these war conditions, the sheer number of soldiers it took out of commission made it somewhat of a priority to figure out what was causing this disease and how it was being transmitted. That's very interesting. Preliminary research had already put forth body lice as the main suspect for transmission.

The disease could be transmitted through the inoculation of blood from an infected person, but not plasma alone. Infections continued to occur throughout the winter, which ruled out flies or midges or mosquitoes, which wouldn't be able to overwinter as well as the body louse. And units that had more body lice had more trench fever or unenched fervous. explained pyrexia, which is what it was often put down as before, like, trench fever became a more popular term. Okay. And efforts to control lice had led in a few instances to a reduction in the incidence of

this pyrexia of an unknown origin. And by the way, control efforts were, like, next to impossible. Mm-hmm. There would be, like, a steam disinfestor or something that it was, like, rarely operational. If you were in the trenches, you were there dug in for a long time. And so it was like, okay, the goal was to shower at least once every two weeks. So like that was the standard. And that is just not frequent enough to completely rid yourself of lice.

Yeah. And so there was a study in 1915 that found that 95% of soldiers were infested with body lice, with an average of 20 lice per soldier, with 5% of soldiers having 100 to 300 lice each. Oh, my God. Can you imagine how itchy that would be? No, it sounds terrible. Yes. And so despite this evidence, though, in support of the body louse, there was still debate over the root of transmission.

And so a couple of research commissions were set up by the British and the Americans. in a very bureaucratic fashion, which meant that the studies themselves didn't start until closer to the end of the war. And the results would be published too late to do much to stop the spread of the disease. But still, the commissions made a few important and, in my opinion, like impressive observations during a time when there were a lot of other deadly things going around. And when medical and microbiological knowledge and technology isn't anywhere close to what it is today. I should also note that this was done through the use of human volunteers,

quote unquote, because like you mentioned, human body lice don't feed on non-primates and lab animals aren't susceptible to trench fever. So these studies found that it was indeed the body louse responsible for transmission, or more accurately, louse poop. Yeah. It wasn't carried in the serum but in the blood itself. All it took was one louse who became infectious five days after feeding on an infected person and could remain infectious for at least four months. Wow. Even though they, I don't know how long, I thought the average lifespan of a body louse was like one month. I was, I was just about to ask you, how long does a body louse live? I don't know the answer to that. I thought I saw in one paper, it was comparing the different lifespans of the vectors of different

Bartonella species and I thought a body louse was was pretty short but maybe there maybe if you keep them if you maintain them maybe that one month is like yeah four months is like your pet louse one month is like yeah your trench louse yeah um and they also found that a person with trench fever could infect lice for at least 443 days after first showing signs of illness. Whoa. Yeah. And that the pathogen, which was still unknown, did not seem to be able to be transmitted vertically from parent louse to offspring. I mean, 443 days, I feel like that explains why the commission took so long to get these results published.

They were just like, still infectious, still infectious, not done yet. For sure. Yeah. They're like, well, we're still going. And like at least 143 days. Yeah. And so while this info would have been, you know, nice to know during World War I, at least it would be useful in the next war. Not that people knew there was going to be a next war.

But World War II didn't have as much trench warfare as World War I. And also the use of DDT had substantially reduced the infestation rates with lice. And so it just wasn't much of a problem at all, Trench Fever. Hmm, okay. And even though a lot was known about the disease and its transmission, the causative agent of Trench Fever was still unknown and wouldn't be described until 1961. Wow.

Yeah, by J.W. Vinson, which I think gave his last name to another species of Bartonella, Vinsoniae, maybe. Okay. I think that infects dogs? I might be wrong. That sounds familiar. Yeah. Who initially named it Rickettsia Quintana.

So Quintana, like you mentioned, is from five-day fever. But later studies showed that it wasn't a rickettsia, even though it seemed like one, because it could be cultured, meaning it wasn't obligately intracellular. And so it was put in the genus Rochalimea, which was changed to Bartonella. when the two genera were merged, like I mentioned earlier, in 1993. And once the organism could be cultured, different antibiotics could be tested to see which were effective, and sporadic outbreaks became more manageable. But the bacterium didn't disappear just because there was no more trench warfare. Starting in the 1990s, trench fever has made a substantial comeback, as I'm sure that you will

talk about, Erin, and already have touched on a bit. But before we get to that, I need to go back a little bit or a lot bit because I started trench fever in kind of the middle of the story. Although the conditions during World War I trench warfare were pretty perfect for the proliferation of Bartonella Quintana, the relationship between the bacterium and humans goes way back. Okay. We already know that Bartonella in general evolved with their vertebrate hosts, but in the case of Bartonella, Quintana, we also have hard proof of this. Researchers found Bartonella Quintana DNA in the dental pulp of someone who died 4,000 years ago in southeastern France.

Very cool. Dental pulp. And pathogen DNA is the best. It is almost as good as coprolites. Oh, God, do I love a coprolite? Yeah. And then there was also a study showing, Evidence of infection in Napoleonic soldiers from around 1812.

And those soldiers, there was actually a 20% prevalence with this pathogen. Man, so 4,000 years minimum. Uh-huh. Oh, it's going to get even cooler. Stop. How? Okay. So there's been other archaeological research that has, like, found evidence of infection

all across Europe and in some other places. And so the fact that, like, it was first described during World War I was probably just because of, like, the conditions, right? Previously, it was probably grouped in with just fever, like general fever in the pre-germ theory days. And actually, one paper made a note that, like, this lack of distinction among fevers may have been why in some years mortality from fever was really low. So, like, if there was a lot of trend. fever going around. Then everyone had a fever, but nobody was dying. Mm-hmm. Yeah. Fascinating. Okay. Okay. So Bartonella Quintana and humans have been cozy with one another for probably as long as the

human body louse has been with humans. But how long is that? Ooh. Tell me. Apparently around 72,000 years, which is when it diverged from the head louse. And that's also around the same time, Aaron, that the use of clothing increased. And as humans began, they're out of Africa migration. So it kind of spread with humans as humans moved and started wearing clothing. O.M.G. Isn't that very cool? Dude, lice, I'm telling you.

I know. Very cool. So Bartonella became specialized on. humans and the human body louse, for the most part. More recently, though, it has been detected, the Bartonella Quintana, in a couple of monkey species, including macaques. Yeah. And researchers were actually able to inoculate macaques and produced chronic bacteremia. Okay. So it's unclear how prevalent natural infection is with this bacterial species in different

species of monkeys, but it's possible that the bacteria spilled over into humans. from non-human primates, either more recently or a long time ago. It seems like it would be a long time ago. I don't know for sure. But regardless of how exactly Quintana came to be, this pretty specialist bacterial species is a contrast to our next and last Bartonella species, Bartonella Hensley. Ooh, I'm excited about this one.

Me too. Do we need a break first, or should we just go there? I think let's take a break and then wrap it up. Great. Okay. Quick break. Okay. So now it's not where we go off the rails, but like we are, I think we're on a different train on the same rails. Oh yeah. Right? Yeah. Okay. We've, we've hopped in a new car. Definitely a new car. Definitely. Yeah, new car. So Bartonella Hensley, aka Cat Scratch Disease. So this is a species of Bartonella that commonly infects cats, feral, and domestic. And between cats, it seems to be transmitted by the cat flea, tinacephalides, philis, which makes sense based on what we know so far about Bartonella, right?

These are tend to be vector-borne species. But humans, for the most part, become infected from contact with a cat directly, specifically from scratches or bites. Wait a second. Uh-huh. But how? In many parts of the world, like 50% of cats have evidence of infection with Bartonella heads. presently, current or past infection. Sure. And just like Bartonella, species that we've talked about that are specific to humans, can maintain chronic bacteremia without any symptoms of disease potentially.

That's what happens in cats. So in cats, they get infected from fleas, like cats have fleas, and in general, they don't have any symptoms of disease, but they can maintain a chronic state of having these bacteria in their bloodstream that can then somehow, Aaron, be present in their claws or in their mouth. Yeah, that's the part that I'm struggling with. I mean, I don't have a great answer to it. Is it in their saliva? I think it maybe perhaps it could be in their saliva, but also like cats' gums bleed a lot. Have you ever looked inside a cat's mouth? I I mean, but I just, the claws and the mouth, like, it, cat fleas don't bite humans. No, in general. And that is not how people get infected. It is possible, like, it is physically

possible to get infected through a vector with Bartonella Hensley. But in general, people get infected from cat scratches and bites. I need more info on this. I'm struggling. So that's all I got for you, Aaron. I mean, that's not all I got for the biology. I was like, that is a really short one. Wow. Yeah, no. Yeah, I mean, it is very interesting, right?

Because in general, it's a bacteria that's found inside of cells, mostly in red blood cells and endothelial cells. But it finds its way into the saliva and claws of cats. I'm baffled. I mean, maybe it's like when cats. scratch or bite people, maybe there tends to be, you know, action more than just a little, little kitty scratch. I'm going to think about this as I'm trying to sleep tonight. I don't have a great nothing that I read talked about it. Not weird. That's so strange. So off the top, clearly, this is a weird one, right? It's different than other species we've covered. It's also a very

different illness that is cat scratch disease, okay? In general, it is fairly mild and self-limited. It most often occurs in kids, but that's probably more likely due to exposure than susceptibility. It also can happen in older people as well, in anyone, any age. And it looks like this. First, about three to ten days after a bite or scratch, you'll get a little lesion on the skin, usually quite close to the wound, just like a pushtual or maybe a little scab. this will crust over, and then usually over the course of a few weeks, you'll start to develop

swollen lymph nodes, just a few, like one, two, et cetera, just on one side, the side near wherever the bite was. So if you got bit on your arm, then maybe the lymph nodes in your armpits, if you got bit on the cheek, maybe under your neck, behind your ear, wherever. And then maybe around that time as your lymph nodes start to swell, you might have some mild symptoms like a fever or body aches or joint aches just feeling cruddy. But really, it's just these swollen lymph nodes, and they can stay swollen for quite some time. It can often take about seven weeks or more before they completely resolve. In some cases, like 20% of the time, they can persist for six months to two years. Whoa. Yeah. And,

about 10% of the time, this swollen node will kind of burst out to the surface a bit so you'll have like pus draining from it. But- Ikees, that sounds uncomfortable. Yeah, it's definitely uncomfortable. But that's rare. That's like 10% or less. Usually it's some swollen lymph nodes, self-limiting, and it goes away.

So it's already a lot of weird things. in humans, this bacteria for some reason is infecting tissues in our lymph nodes rather than directly infecting our red blood cells. Where does it go in cats? It goes into their red blood cells, but it doesn't cause disease, and it doesn't cause any of the angioperative or the skin disorders that we've seen with other Bartonella that doesn't happen in cats. Usually they have no symptoms whatsoever.

And it doesn't go into their lymphin. notes. Not enough to cause them to swell. Okay. But it gets even weirder because in people who are immunocompromised, Bartonella Hensley is a very important cause of baciliary angiomatosis. That disorder that we already talked about caused by Bartonella Quintana. Right. And with Bartonella Hensley, it can actually be even worse because these vascular tumors can be found on the liver. This is sometimes called an entirely different disease, pelosis hepatis or baciliary polosis. That just means these tumors on your liver. Okay. And in both immunocompromised as well as immunocompetent people, very rarely Bartonella Hensley can infect the nervous system and cause things like encephalopathy.

There's a few cases of it causing like neuropsychiatric disorders potentially. it's very bizarre. Yeah, this one is definitely the weirdest. It is definitely the weirdest. And it's a zoonotic disease, right? This is a species of bacteria that's closely associated with cats. It can also infect dogs, and in dogs it can actually cause endocarditis. Okay.

But in cats, it doesn't tend to cause any disease. None of these symptoms seem to happen whatsoever. And so all of this is to say that that's part of why we really don't understand a lot about the pathogenesis of Bartonella in general, this species or otherwise. Because even here where we have a zoonotic species, you would think, well, at least we have an animal model. It's in cats. 50% of cats are infected. But they don't manifest the same disease. So we can't study this human disease in cats or in other animals. Bartonella is like, this is tip of the iceberg type thing where you're like, oh, I see what's on the surface. This is going to be very straightforward.

And then it's like, just kidding. Right. We severely underestimated them. Yeah. So for the last and final time, Aaron, can you tell me how we got here where Bartonella Hensley came from? Like, what's up with cat scratch disease? I'll just dive right in yet again. Please.

So I was trying to think of like what is the take home for all of us? Is there any sort of like unifying theme? And the only thing that I could really think of was that the growth of knowledge doesn't happen in a predictable way or rarely happens in a predictable way. And that we may only recognize how things are connected in retrospect and like rarely, if ever, at the time when we're examining them. And I think this can definitely be said for the two Bartonellas we've already talked about, bacilliformis and Quintana, but I think it's especially true for our last Bartonella, Hensley.

So not only did it take until 1993 for this bacterium to be put in the Bartonella genus, along with Quintana during that reshuffle thing or merge, it was only 10 years before that that it was seen for the first time, despite the disease itself, cat scratch fever, being known for 100 years and clinically described for 50 years. Goodness gracious. Yeah, so let's get into it. First off, there is most definitely evidence of ancient infection with this bacterium. Again, using dental pole.

Researchers found Bartonella Hensley DNA in 800-year-old French cats from the 13,000. 14th and 16th centuries. And it's likely that cats have been infected with this bacterium since cats have been cats, or at least since the cat flea began biting cats. And since Bartonella Hensley is also able to infect humans, it seems also likely that humans have probably been prey to this pathogen since humans and cats began associating with one another, which was around 7,500 BCE. But the earliest description we have of anything resembling cat scratch disease or cat scratch fever is from 1898, when a physician described a condition similar to and thought to be,

in retrospect, of course, cat scratch fever in the context of oculoglandular syndrome. That's all I don't really know. And the disease got its official clinical description. only in 1950 by Robert Debray, professor of pediatrics at the University of Paris. Okay. Dr. Debray was no stranger to this disease, having treated a 10-year-old boy in 1931 who had a cold, fistulated aditis that healed quite nicely on its own. And the doctor, though, was struck in particular by the severe and numerous cat scratches

on the same hand as the same side as the adenitis. Oh, gosh. I know. The boy's mother said that although her son had been told not to play with the cats, she found him in his room with a bunch of the kittens, and they were all hanging out together, and he just couldn't resist, which I think is really cute. I hope he had fun.

I hope it was worth it. Yeah, yeah. It healed nicely. Yeah, exactly. So initially, Dr. Debray was convinced that this was like a form of tuberculosis, but he was unable to isolate the tuberculosis bacterium. So then he figured, okay, it must be some sort of bacterial infection from the cats. But again, none of these bacterial assays or investigations turned up anything.

The wound healed, the kid recovered, but the case stuck out in the doctor's mind. Over the next years, Dr. DeBray saw additional cases of adenopathy that cleared up on their own, all of them with cat associations. And he took to calling it cat scratch disease. But despite a regular influx of cases, he was never able to find or isolate a causative agent. And Debray wasn't the only one to recognize this strange illness. Lee Fochet, a professor of microbiology at the University of Cincinnati in Ohio,

had also noticed it. And when Debray visited Cincinnati in 1947, for, I believe, a conference, they struck up a conversation when they realized they both had a special interest in an experience dealing with this cat-associated illness. How fun. I know, right? And they had even come up with basically the same name for it. So Debray called it cat scratch disease while Fochet called it cat scratch fever. Oh!

Debray was super excited to find another person interested in it, and especially so when he learned that Fochie, had developed a diagnostic antigen test. And he suggested, like, oh, you know, let's put our minds together. We'll publish two articles about this disease. Yours will be about the diagnostic test. Mine will be about the clinical disease. But Foshae was like, no, no, I'm not a clinician or pediatrician. I'm a bacteriologist and a virologist.

And I won't publish anything until I find the causative agent. So Debray was like, oh man, like, bummer, this stinks. And it took him a few years to get up the nerve to publish anything on cat scratch disease, which he finally did in January of 1950. The publication of his description got the wheels turning for other people, and additional work on the disease continued with more antigen diagnostic tests being developed and experiments infecting cats and humans. But like Bartonella Quintana,

much of the progress had to do with describing the disease itself rather than isolating the causative agent. But that changed when in 1983, the bacillus was discovered in lymph nodes of patients with cat scratch disease. I know, 1983. 83, my goodness. So recent.

Yeah. And even then, in 1983, the researcher was just able to say, that this was a small gram-negative bacillus. It took five years for the bacterium to be successfully isolated and cultured. And then it was named first Rocholimia Hensley and then changed to Bartonella Hensley. Hensley after Diane M. Hensel, who isolated many of the original strains. Okay. This species, like Bartonella Quintana, has made headlines over the past

few decades, as you mentioned, due to its emergence as a threat for people who are immunocompromised, and also, as I saw in one paper, as a possible occupational hazard for people who routinely work with cats, like veterinarians. Yeah, veterinarians. Uh-huh, definitely. So, Erin, let's wrap this very interesting and all over the place episode up by talking about where we stand with all of these Bartonella today. Oh, let's try, but here's the problem, Aaron. It was very difficult to find any kind of numbers in terms of overall infections, which is what I usually try and find, like current status, et cetera. To be honest, I'm not

surprised by that. I know. And the other thing is that a lot of the papers that I found that did cite some numbers were like 10 years old. So we'll just go with what we've got, which is, I'm not going to lie, it's not great. Okay. Yeah. We'll start back at the beginning with Bartonella Basiliformis from a 2009 paper that cited data from the Peruvian National Institutes of Health that was congregated from 2004 to 2006. So this is old data, y'all. But they cited over that two-year period in the early 2000s more than 26,000 cases of Bartonellosis. Wow. Yeah, it's more than I thought.

And because the mortality rate can be high, this paper was saying that it can be estimated that just in Peru, and remember this is in at least three different countries, hundreds of people are likely dying every year from this disease. And how effective is antibiotic treatment if you get it early enough? It's a good question. It seems like it is effective, especially because a lot of the mortality is from secondary infections. so if you're able to tamp down the primary infection. But again, I don't have numbers on that. Okay. Some other stats, just to kind of get an overall sense of this, people have reported that in some endemic areas in Peru, up to 45% of people that live in those areas under 21 show

exposure. So they show evidence of having been infected at some point. So that kind of not only says this is a prevalent disease, but also maybe. Maybe there's more asymptomatic or mild infections than we thought. Mm-hmm. Okay. Right. So that's Bartonella bacilliformis.

Bartonella quintana, so difficult to get numbers on. We know that it's a big problem for people experiencing homelessness, both trench fever as well as endocarditis. Mm-hmm. The best I could find is that in studies where they have tested people that have been found to be infected with lice, anywhere from eight. to 50% of people were seropositive for Bartonella Quintana. So that doesn't tell us that much as far as actual numbers go. But I think it does tell us that this is probably far more prevalent than we think. Yeah, I mean, absolutely. And like trench fever, I think people think, oh, it must be a disease of the past, but it is not the case. And like I said, in terms of bacilliary angiomatosis, that

is very low prevalence, like one in a thousand, of people living with HIV, though it can happen in other people as well. And then we get all the way back around to Barnella Hensley. What's the prevalence of this? Who knows? The CDC estimates about 22,000 cases every year with about 2,000 requiring hospitalization. Wow. Okay. That's more than a thought, to be honest. than I thought as well. So we know that in a lot of places where they've tested cats, seroprevalence in cats can be quite high. But even in some places where they've tested people, they have found that anywhere from

5 to 30% of people are seropositive for Bartonella Hensley. Lots of people around cats. Also, only about 25% of infections are actually strictly associated with cats. So. What? Like a known source. Like, here's my cat bite. here's my infection.

Erin. Yeah. Hensley is by far the most strange. It's a different car. Yeah. Yeah. And then the really tough thing is, quite honestly, there are so many more species of Bartonella. And there are so many case reports out there of cat scratch disease caused by this new species or trench fever caused by this other species, et cetera, et cetera. There are species of Bartonella associated with so many different mammals. Many of these can potentially cause zoonotic disease. They can spill over into humans, whether from whatever vector potentially, right? And so I think in terms of like where is the

research going, one of the biggest things we have to get a handle on is really just the breadth and depth of this genus of bacteria worldwide. What is its true distribution? What the heck are the details of how it causes disease? We really don't know a lot. For people who are interested, we do have more detail on how it causes neo-angiogenesis, like the formation of new blood vessels and things. So we'll cite those papers. But we still don't know a ton. Vaccines, we don't have any. I will link on our website to a paper that was interesting that found potential targets because there is at least a theoretical possibility that people do mount a protective immune response to infection if they don't just become chronically infected. Okay. But, you know,

it just, it comes down to both do we have the baseline knowledge that would be necessary, first of all, and is there any funding for it? And I don't know. Yeah. So that's a bunch of different diseases and a few different bacteria. Probably more than anyone bargained for. Definitely. I mean, we did try and warn them three episodes. Yeah. Maxisodes. I like that. Yeah. Should we do sources?

We should, definitely. Okay. I have a ton, but I'm going to shout out four that I found really helpful. one by Anstead from 2016, the centenary of the discovery of trench fever and emerging infectious disease. One by Carithers from 1970, cat scratch disease, notes on its history. One by Eiler from 1996, Bartonella Bacilliformis, dangerous pathogens slowly emerging from deep background. And finally, one from 2021 by McKee at all. Bats are key hosts in the radiation of mammal associated Bartonella Bacte. I had a lot of papers for this one. I think my favorite of just an overview of all of the different species of Bartonella was just called Bartnolosis. It was by Manguania at all, and I'll post that. And then there were a couple of others like Bartonella species throwing light on uncommon human infections. There was one that was all of the different Bartonella species called historical pathogens of emerging significance. There's a bunch of,

good papers and we'll post every single paper on our website, this podcast will kill you.com under the episodes tab. We sure will. Thank you to Bloodmobile for providing the music for this episode and all of our episodes. Thank you to the exactly right network of whom we are very proud to be a part. And thank you to you listeners. We really appreciate you listening. Let us know how you liked this one.

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