Ep 226 Glanders: Straight from the horse’s mouth

In March 1911, I was at work on an obscure case of disease in an Arab pony in the contagious ward of the Punjab Veterinary College, Lahore, India. At first, there was nothing to lead one to suspect glanders in the pony, and I made several cultures on gelatin agar from an abscess which I opened. The resulting growths aroused my suspicions, which were confirmed. It was during the night of the third March that I first became ill with severe headache and a temperature of 102 degrees Fahrenheit, 39 degrees Celsius. There was no reason why I should connect my illness with my laboratory work, and I did not.

All the fourth March, my temperature was 101 degrees Fahrenheit, but I continued to go about in the usual way. However, on the fifth, I had acute pain between the diaphragm and liver. It was the first internal symptom I had. and seems to point to the bacillary infection as having taken place through the alimentary canal. From the 4th March, when my temperature first rose, a period of three weeks elapsed before the first external lesion appeared on my left hand.

During this period, I had intermittent fever. The case was diagnosed as malaria, and I was treated for this, pending further developments. I was beginning to think I was throwing off my attack of fever when on 24th March I knocked the back of my left hand. The next day, a very painful, deep-seated swelling and redness appeared on the back of my hand. By evening, the pain was intense.

No sleep was obtainable, and my temperature rose to 102 degrees Fahrenheit. The pain necessitated morphia for three nights, and as no improvement set in, I insisted on an incision. A scalpel was pushed into the prominent place without an anesthetic, but no pus had accumulated. Cultures were made and gave a growth which was said to be a bacillus which was most like Glander's, but yet showed differences. My temperature varied between 100 and 102 degrees Fahrenheit, and now red lines began to run up my wrist and forearm. The invasion of my lymphatic system seemed to receive a check at the shoulder. Then day by day, the red lines began to recede and fever to subside. During April, May, and June 1911, frequent operations were performed on my hand

and the two lesions on my forearm. From one of the abscesses on the forearm, I made my own cultures. After 48 hours, the growth was luxuriant, and I was struck by the resemblance to Glander's cultures. I had each year destroyed many horses on such evidence, and yet when the facts showed that I myself had the disease, I could not bring myself to believe it. I gradually persuaded myself there must be some mistake, and as time went on, became nearly convinced of it. Instead of facing the facts, I made no more cultures and destroyed those I already had.

The surgeon who remarked that, quote, must have been very near the truth. Not counting the smallest of the incisions, I have been operated upon 45 times, and of these, 27 operations were done under a general anesthetic. The disease commenced on 4th March 1911, and on 25th June 1913, my last lesion healed. I must finish by saying, that I should not have had the slightest chance of recovery had it not been for the patience and generosity shown to me by the surgeons who treated me and for the kindness of numerous friends who looked after me during my somewhat horrible experience. Thank you.

I'm sorry.

What? Right? Speechless.

100% speechless. Sorry, that was a long inhale of what?

Yes. So this was an account of a researcher, I think it was a veterinarian, who contracted Glanders and then wrote about his experience. Erin, this was such a small snippet. Part of his arm was amputated because of Glanders. And then, so this was published. He wrote this up and published it in 1913. And then two years or three years later, he published a follow-up About his recurrence.

Because it came back.

It came back. And he was suffering from both Glanders and malaria at the same time. And it lasted another two years for him to recover from that.

I can't believe he was alive.

I know.

Fascinating. Brutal.

Just brutal.

Absolutely horrible.

Yeah. My somewhat horrible experience, though, he ends it.

Only somewhat.

It only lasted two years.

Only lasted two years.

And then had a recurrence.

Right.

This was pre-antibiotics.

Pre-antibiotics. Post-antiseptic technique, pre-antibiotics.

Pre-antibiotics.

So you can read the full account by searching for Glanders in Man from the Journal of Comparative Pathology and Therapeutics. It was published in 1913 by S.H. Geiger.

Okay.

Hi, I'm Erin Welsh.

And I'm Erin Allman-Updyke.

And this is This Podcast Will Kill You.

Welcome to Glanders.

Glanders.

So many people are going to have never, ever heard of this because I had never heard of it.

I had never heard of it either until I was watching The Americans. And the episode was called Glanders. And I was like, that's weird. And then it turns out. What season is that?

Oh, Erin. Let me look it up. It doesn't matter because I just never finished it. It's giving me motivation to go back to that series.

It's such a good show.

It really is.

It's really phenomenal.

Okay.

It's season four, episode one. Oh, okay.

I probably didn't make it that far.

Oh, you should definitely, especially I would say, okay, we don't need to go here, but like the way that it concludes the entire arc of the show is phenomenally done.

I love it. Okay. Will do. Check.

So Glanders, what the heck is it? It's a bacterial infection. It impacts horses and humans, as you heard in our firsthand account, and cats and some other creatures potentially. Okay. Really, really deadly.

Really, really horrific. I can't wait to.

Tell everyone about it. Yeah. And before we can do that, though, it's quarantini time.

It's quarantini time.

What are we drinking this week, Erin?

We're drinking typhoid mayor-y.

Like.

Horse. You call it a mare.

It works well written down.

It does.

So I stole this. I lifted this from a– I came across it in a paper published this year called Death of a Pale Horse by C.R. Eliot about Glanders and Warfare in North America from 1812 to 1865. And I was like, Typhoid Mary, brilliant.

Thank you.

I love when that happens in a paper.

Tell us what's in it, Erin.

Yes, yes. It is an iced chai latte. So oat milk. Oat milk. Because mares eat oats and dozy doats and little lambs eat ivy. Kittle eat ivy too, wouldn't you? So it's oat milk. It's chai tea. It's maybe maple syrup, maybe honey, whatever you're feeling.

Yeah, make it a little sweet.

Extra things.

Yeah.

We'll post the full recipe and you can see it written out. So, you know, you get it on our website, thispodcastwithkillyou.com and all of our social media channels. So make sure that you are following us there. Yes.

On our website, you can find all sorts of things. You've heard the spiel. Check it out.

I love it.

Let's get to Glanders. Okay.

We'll take a quick break and dive right in. So So the pathogen that we're talking about today, the causative agent of Glanders, is a bacterium called Burkholderia mallei.

Great.

Yeah. I pronounced it for you.

Thank you.

It is a gram-negative rod-shaped bacterium that is an obligate pathogen. So this is very different than many other bacterial species that we've covered on this podcast, which can exist as free-living organisms in the environment and replicate no problem. This particular bacterial species is an obligate pathogen on mammals, meaning that it only can live and replicate inside of a host.

It can live intracellularly, but it also can live in our bodies outside of cells while it's moving around. Okay. Now, there are a couple of other similar related bacterial species that I do want to mention. Yeah. Because they are perhaps more important or more common causes of disease, especially in humans. And they can be really similar. Okay. So one is a bacterial species called Burkholderia pseudomallei, like fake mallei.

Love that. And this causes a disease in humans called melioidosis.

Yes.

Very, very similar bug. But the big difference is that pseudomallei can breed free living. So it is something that you are exposed to from the environment, from soil and things like that. And it's just an opportunistic pathogen. Burkholderia mallei, on the other hand, is... very similar bacterial species, but with 1,200 less genes and poor survivability outside of a host.

Really? Okay, so then I read somewhere that it, And maybe this was before the distinction was made between pseudomallei and mallei, that it can live for six weeks in the soil in infected areas.

So it can live, but it's not replicating.

It's not replicating. Yeah, exactly.

But it can survive on surfaces or in soils. Yes, that is true.

Okay.

Yeah, 100%.

But it makes sense then, given this sort of obligate parasite lifestyle, how it was able to be eliminated from so many places. Yes. In a relatively short time span.

Yes.

Combined with other things. Spoilers. Spoilers.

But yes, that's very, very true. There's another Burkholderia species that's important for humans called Burkholderia sepatia, which is a very common cause of disease, especially in people with cystic fibrosis. So two more episodes we'll have to do someday.

Burkholderia, we'll do them all.

Okay. But today... We're just talking about Burkholderia malii. Glanders. Glanders.

And Farsi.

And Farsi, yeah.

F-A-R-C-Y, in case anyone was curious.

So this is a bacteria species that causes disease mostly in... I learned a new word, solopeds.

Yes.

That was a new word I never learned. It means one hooves. So these are animals like horses, donkeys, and mules, which have just one hoof rather than like, you know, cows and pigs that have two hooves. Little beep. And we're going to talk about what this disease looks like in those animals, so in equines like horses and donkeys, but also it can cause disease in humans. Humans are considered rare hosts for this pathogen. Usually we have to be exposed like in pretty close contact to infected animals such as occupational exposure or like in our firsthand account, you work in a lab with this organism.

But.

Humans are not dead end host, first of all. It is still possible to transmit person to person, though it's very, very rare. And we don't really have a lot of reports of this happening. And there are a lot of other mammal species that can also be incidental hosts. Right.

For instance, unicorns.

For instance, unicorns. I'm wearing a unicorn t-shirt. Oh, I was going to say unicorns would just be like a typical host because those are solo pets.

Yeah, but they're rare because so it's like, you know.

Oh, this is going to be a fun episode, Erin. I like it. I was going to say like carnivores as an example.

Oh, yeah. Yeah.

If they feed on the carcasses of sick animals, lions, other cat species.

Wolves, cats.

Sheeps and goats can occasionally get it, but they are relatively resistant. Same thing with cattle. And pigs are apparently quite resistant. Why?

How?

Why? Great question.

Who knows?

I don't know. Okay. It seems like the most common way that animals are being exposed is actually through contaminated food and water sources that get contaminated either from respiratory secretions or from the skin wounds and secretions from skin wounds on infected animals. So they're either ingesting it or, you know, they could inhale it. They could have direct skin contact. So while, like we said, this is not a bacterium that replicates in the environment, it can survive pretty well in the environment.

Okay.

If it's in the right environment, like, say, a nice, juicy, warm, kind of wet stable where you might keep a horse or a donkey, it is susceptible to desiccation. It's susceptible to sunlight. It's really easy to kill with our modern– common disinfectants like alcohol and bleach and things, but it can potentially persist on surfaces. In humans, there's a few main ways that we get infected. Contact with broken skin, so you can get infected via the skin. Same horses can do the same as well. Or contact with our mucous membranes, again, from secretions from infected animals. Or we can inhale it, in which case then the particles are more likely to cause a respiratory infection.

What about ingestion?

Yeah. I mean, in theory, if you get contact with your mouth mucus membrane, it's probably not going to survive your stomach necessarily unless you got a lot of it in your mouth somehow. But it could definitely just infect you via your mucus membranes.

So the firsthand account was like, I think it was in my alimentary canal because there were no respiratory lesions there.

I mean, it could have just been his hands, though.

That's what I was thinking. And I was like, and he because he was like, well, I've never I've worked on Glanders so many times and I've never been infected before.

And.

First time for everything, I guess.

Tiny little cut on your fingers that you didn't know were there and you weren't wearing gloves because it was 1911. I don't know.

And what's the infectious dose? Oh, great question.

No idea.

Okay. Honestly, it makes sense. The modern day literature on Glanders is pretty sparse.

It is so sparse, Erin. I have so many more questions than answers for this episode. Okay. So let's talk about what this actually looks like. There's A few main forms of the disease that can happen in equines, in horses and donkeys and mules. But they're not necessarily mutually exclusive, first of all. And in addition to like the different body systems that it can infect, there's also acute disease versus chronic disease. So the three main body systems that we tend to see have involvement are the pulmonary system, so lungs. As well as the nasal canal, so like the upper respiratory tract. And then the cutaneous system. So we can see, like you said, farsi, which is when the skin is involved. In acute glanders, which is more

likely to affect donkeys and mules, the symptoms usually start with a fever. And then this nasal discharge, which is usually quite purulent, so like a lot of what looks like pus. And can pretty rapidly progress to ulceration of the nasal septum. Of course, the animal is going to look really bad. They're going to be lethargic. They're going to seem depressed. They're not going to be eating. So they're going to lose a lot of weight and end up emaciated. This disease can then progress to involve the respiratory system and the lungs, resulting in a pretty severe pneumonia.

And it's very, very often fatal. In contrast, horses tend to have a more chronic, indolent and prolonged disease. This can start with kind of intermittent or like relapsing and remitting fevers. The horse might have a cough and they might have a little bit of weakness and just sort of not seem like themselves. In some cases, they can get these enlarged lymph nodes, which can then ulcerate and form these wounds that are really difficult to heal. They can also get ulcers in the nose because, again, a lot of times contact is through respiratory secretions. They can have swelling in the joints. The lymph nodes that get enlarged might eventually cause lesions on the skin, these cutaneous lesions that we call Farsi. And then the infection, especially

in horses, tends to spread along these lymph chains and and then eventually to internal organs, which can include the nervous system. And that is often what progresses to fatality in the case of horses.

Okay. How long is the average disease course?

It really can depend. So it can be like a matter of weeks if we're talking acute glanders, but this can go on for months if we're talking chronic glanders. And the incubation period can also range. It's often Between one to five days, so pretty short if we're talking about the acute form. But it has been shown to be up to months, especially in horses, if they're infected via inhalation. And then it's more likely to cause this kind of chronic disease.

Okay. And when are horses, are animals contagious before they start showing symptoms?

It's a great question. It is the secretions from the wounds, from the ulcerated lymph nodes, and from the nasal secretions or the respiratory secretions that are the infectious, that like house the infectious particles. So I didn't see anything in the literature specifically about whether or not We know for sure if animals could be contagious prior to symptoms, but I would guess that the major amount of contagiousness is when they are symptomatic.

And acute versus chronic, how long, chronic, does it ever resolve on its own? What happens at the end of the acute phase? You either develop chronic glanders or die or recover completely?

Yeah, that's a great question. I think it really depends on what kind of situation these animals are in. Because we'll talk about what we do to so-called treat Glanders and spoilers we really don't in animals. And so really it just depends on the situation. It is possible for animals to recover, I think, but I really couldn't find any data on that in the literature because of how Glanders is viewed and how it's dealt with. Okay.

So this bacteria invades your your body in some way and then forms these ulcers internally, lesions externally. And if it progresses enough, like these lesions, like in our firsthand account, they just get worse and worse. More pus, more inflammation until major organ systems are involved, until your nervous system is involved.

Right.

What's the case fatality rate?

It's extremely high. But again, for animals, I don't have great numbers because our numbers are all skewed by how we manage Glanders. Right. And in animals, I'm just now I'm skipping ahead. But in animals, we don't treat Glanders with antibiotics. These bacteria are extremely resistant to antibiotics. And so it is the recommendation of the World Organization of Animal Health. And like the way that Glanders is managed is you eliminate the animal. So animals are euthanized if they are found to be infected. And any animal that has been in contact with an infected animal has to be monitored. If they develop symptoms, then they also have to be euthanized. And it's like really draconian and hardcore. Whoa. Yeah.

And so that's why it's really hard to get like case fatality rate numbers because it is just something that is a really big deal. And so it's managed. if that makes sense. Right.

Yes. It is not treated. It is managed. Yes. Why is it so... What is it about the bacterium that makes it so resistant to antibiotics?

Oh, it's really good at just evading our immune response. A lot of it might be because it's intracellular, but it also just... There's things about Burkholderia that just make it more difficult to treat. It just has like an intrinsic resistance to a lot of different antibiotics.

And this is multiple different. Part of it is that it's intracellular.

Multiple different. So we'll talk about, let's talk about it in humans. And then we'll talk about how we have to treat it in humans. Because even in humans, it's really, really hard to treat. That's why I'm shocked that our firsthand account survived. Yeah. In humans, broken skin, so some kind of break in our skin, is often a primary route of entry. Mm-hmm. If that's the case, then after a few days to a few weeks, there might be an abscess near the site of initial infection that may eventually ulcerate. But often through this time, even, you know, maybe even before an abscess initially forms, you might have kind of nonspecific symptoms, fevers, body aches, chills. You might get some swelling of your lymph nodes, maybe around that

site of infection, or maybe just diffusely, which again, we can see with lots of other infections, so it's kind of nonspecific. But eventually, as this bacteria travels along our lymph nodes, the lymph nodes that are infected can form further abscesses, that if these are untreated, will eventually break down, ulcerate to the skin and actually drain. After another maybe one to four weeks, These bacteria can spread throughout our body and cause severe infection and abscesses in any of our organs. And most commonly, they end up traveling to our solid organs. So things like our liver, our kidneys, and our spleen. And we can see numerous abscesses throughout these organs.

Good God.

If, on the other hand, exposure is via the respiratory tract, then we can have a really severe pneumonia.

Yeah.

So you're going to have, again, fevers, chills, respiratory distress, cough, nasal secretions. It can even progress to having pulmonary abscesses, so abscesses in our lungs, which can then also cause effusions or fluid that collects around our lungs, which you can imagine makes it really, really difficult to breathe. A few cases, and again, we don't have a lot of data on human cases. So a lot of this is just from like individual case reports that this data has been put together. but a few cases have reported improvement.

So an infection that seems nonspecific, fevers, chills, body aches for a first few days, and then improvement, and then a relapse.

Yeah.

How often does this happen? Again, we don't really know. But in any of these cases, whether it's primarily spreading via our lymphatics, eventually getting into our bloodstream and causing a bloodstream infection, or whether it's infecting our lungs and causing a pneumonic infection, It's very often fatal. Case fatality rates in humans are over 90%. It can be a prolonged disease if it's in our lymphatics and in our bloodstream, but in the pneumonic form, it's usually fatal within 10 to 30 days.

And even with treatment.

Mortality estimates are as high as 40 to 50%.

How did we not know about this?

I don't know, Erin.

Hmm. I really don't. That is so high. Over 90% treated, 40 to 50%.

Correct. But it's, again, extremely rare.

Yeah.

It's extremely rare. Is it probably underdiagnosed? Yeah, probably. But it's extremely rare still.

And so when someone is infected, the course of treatment is antibiotics as much as you can. And then how do you deal with the abscesses that form inside your body?

Yeah, it depends on where they are. So the literature at least says for humans, you don't necessarily have to drain them, which is really interesting because a lot of times if you have abscesses other places, we talk a lot about needing to get source control where you have to drain that abscess and you have to clear that abscess before you even have a hope of antibiotics working.

But it's really going to depend on where the abscesses are. Yeah, the literature says you don't necessarily have to drain the abscesses, which is weird and kind of interesting. But antibiotics are incredibly intensive. So you know, Erin, that I don't like the term like big gun antibiotics because it's not good.

But if I used that term, that is the term that people would use here. Because this bacteria is intrinsically resistant to so many different kinds of antibiotics and because it can cause this prolonged and relapsing and very severe disease where it's hard to know for sure if you've eradicated it. The recommendations, which are not even like, they're just sort of consensus recommendations. There's no like official guidance from IDSA because this is so rare.

Yeah.

But that's the Infectious Disease Society of America, by the way. But basically it's IV antibiotics for a prolonged course, like at least 10, if not 14 days of really broad spectrum antibiotics. followed by a year, like six months to a year of oral antibiotics to try and clear this infection.

Or aren't enough probiotics in the world.

Not enough probiotics in the world for that.

Yeah.

And that's if we can actually diagnose it to begin with. And diagnosis is really difficult. Gold standard is still culture, but... like you heard in the first hand account, interestingly, it takes at least 48 hours for this thing to grow. And that's if you have the right medium and if you are looking for this bacterium. We don't have great, like, rapid diagnostics. There's a test that we can use that cross-reacts with the one that we use for melioidosis, that Burkholderia pseudomallei. So sometimes that's used. In animals, we use this really horrific test that uses the same idea as TB skin testing. So it's looking for like a delayed reaction, but they do it in animals' eyes. What?

I didn't know that.

They can do it under the skin, but I think because the, you know, the hide of a horse is quite thick. So I think their eyelids are thinner, so they get a better reaction. So they put this purified protein into their eye and then they look for a reaction like swelling and purulent discharge. That's glanders, Erin.

So we have No great treatment. Case fatality rate still quite high. And control is really the only best course.

Yes. And the only control that we have is early diagnosis and euthanasia. We don't have a vaccine for this at all. Spoilers for later in this episode.

Well, and it's interesting, the firsthand account was he sent off, he did say that he sent off one culture to a research institute to say, make this a vaccine.

Can you make a vaccine?

And he didn't say this is Glanders. He just said, make a vaccine for this specific thing, which does seem a little bit irresponsible now that I'm talking about it. And he's like, but the vaccine had no impact on the course of the infection. Yeah, yeah. But yeah, I can't believe he survived after hearing all that.

I cannot believe he survived. I was just like mouth ajar for that whole firsthand. Like, what? Yeah. Yeah. Because case fatality rate is really, really high.

Really high.

And there's so much that we don't know about this bacteria.

So we've done other intracellular, obligately intracellular pathogens. Rickettsia rickettsii is the first one that comes to mind.

100%.

And I can't remember, is that super resistant to antibiotics as well?

No, it's not. You can treat it with a pretty reasonable course of antibiotics. So it's something else about Burkholderia and Burkholderia malii that makes it particularly resistant to a bunch of different antibiotics.

How strange.

I know. And scary.

But it's really rare.

So Erin, my question for you, because here's what I haven't even talked about. One of the reasons that this thing, which is so rare, is such a big concern for a lot of people is that it is considered a tier one, meaning it has a huge potential for use as a weapon of bioterror because it is highly infectious when aerosolized. It's obviously highly incapacitating. It's quite deadly. So Erin, can you please tell me about this?

Sure, sure. Can do. So No one talks about Glanders anymore.

Anymore?

No. Anymore. Key word. Unless you happen to watch the Americans or work in a biodefense lab, you may have not even heard of the disease, much less chat about it over the water cooler with friends or colleagues or whatever. And this... Relative obscurity of Glanders would come as a straight up shock to veterinarians of the 1800s.

Wow.

For them, Glanders was a widely prevalent, deeply feared disease of equines against which they were powerless. And it's easy to forget, I think, just how dependent on horses and mules and donkeys much of the world used to be before they were replaced by cars and trucks and buses and other machines.

Yes.

For thousands of years, horses held a revered and valued place among domestic animals, and their well-being was really closely guarded. In fact, some have suggested that the first veterinary schools, which were established in France in the mid-1700s, were founded not because of devastating cattle diseases like rinderpest, but horses and glanders. I mean, why not both, I think, but...

But I think that even, yeah, even the fact that Glanders was part of the rationale for veterinary training, I think puts this disease into perspective, how important it once was. And so today I want to take us through the history of Glanders and what its rise and fall can tell us about the contagion debate, war horses, and bio-warfare.

I can't wait.

So Glanders goes way back to at least 425 BCE when Hippocrates described symptoms of the infection. And in 350 BCE, Aristotle mentioned a disease of equines, quote, the ass suffers chiefly from one particular disease, which they call mellus. It arrives first in the head and a clammy humor runs down the nostrils thick and red. If it stays in the head, the animal may recover. But if it descends into the lungs, the animal will die, end quote.

Hmm.

And throughout the following centuries, Glanders attracted attention here and there as it infected horses and other equines in Europe and Asia, and early veterinarians argued over its cause and treatments. So for instance, in a book on husbandry by Fitzherbert published in 1523, he describes Glanders as contagious. But a book about 140 years later called Markham's Masterpiece discusses both Glanders and Farsi, the superficial form of but doesn't link the two and suggests that only Farsi sores are contagious.

But Glanders is like a, you know, an imbalance type of thing. Exactly.

Yeah.

Another writer from the 1660s wrote that Farsi could be more or less severe, depending on if the moon was waxing or waning. But he also linked the two diseases. Interesting. And he advised people that, quote, as soon as you perceive the least sign of Glanders, you must separate the sick horse from all his companions, So knew that.

It was contagious.

Knew that it was contagious. But this debate continued. It continued, you know, whether Glanders was contagious, whether Farsi was contagious, whether they were one and the same disease or different diseases. I mean, this went on until the 19th century. And I know that we have the benefit of hindsight today, but it is amazing what a chokehold the humoral theory had on science and medicine.

Yeah.

Where you're just like the mental gymnastics to ignore contagion in this situation.

Right. Intense.

Yeah. So, for example, in 1817, a veterinary student died of glanders after injuring his hand while performing a dissection on a glandered horse. A professor looking into the case took samples from the student's body and then inoculated two donkeys, both of which developed Glanders. The professor concluded that Glanders was not contagious and that what caused the student's death was actually cadaveric poison. What? Yeah, like he got sepsis from dissecting the horse.

I mean, he did. From Glanders.

From Glanders.

The cadaveric poison in question was Glanders.

Yeah, but no. Wow.

Okay. Wow.

Yeah. Yeah. So that was a little bit, I think a few authors were like, that was an unfortunate conclusion. That is really quite unfortunate.

You were so close and you just missed it entirely.

But fortunately, this opinion that Glanders was not contagious was increasingly in the minority as people recognized that not only horses and donkeys could get Glanders, but also, of course, people, cats, dogs, and other animals were susceptible. So by the mid-1800s, the debate had largely been settled by a series of experimental infections.

And just like the growing number of veterinary professionals who were trying to turn what had always been an art into a science. So like as more people came into the field, they were like, let's figure out what this is and treat it or prevent it. Why? Why did veterinary medicine grow so much during this time? Truth, but also money.

Money.

It's always money.

It's always, I mean, yeah. Horses were an extremely valuable resource, and this was never truer than during times of war. So Glander's cases in humans remained fairly sporadic throughout much of history, but this was certainly not the case for their horses. Since at least the Crusades of the 12th to the 14th centuries to the First World War, Glanders posed a considerable challenge. Horses and other equines were not just useful in war, they were essential. And so when they fell sick with Glanders, people tried anything. They're spraying urine into a horse's nostrils, forcing warm chicken guts rolled in salt down its throat.

What?

Yeah, and even more upsetting ones that I don't even want to go into because I don't want to put that image in your head.

No, I already have such a bad image already.

There are worse ones out there. Let me just say that.

I believe you.

But these didn't work, of course. Given that there was no effective treatment for glanders, the only options were prevention and control. And they were practiced pretty much the same 150 years ago as they are today. So Glanders had probably been introduced to North America during the American Revolutionary War or the War of 1812. But by the Civil War, it had grown into a widespread pressing issue. Wars or conflict during this time, during the 1800s, were powered by horses.

And when a disease swept through that slashed the number of healthy horses, the scales could easily tip in unexpected ways. So to put this into perspective, just how important and how prevalent horses were, during the first two years of the Civil War, the Union Army consumed over 284,000 horses and mules. Consumed not meaning like eaten, but like they died, they became injured, they were used in some way. So they went through that many horses and mules.

Whoa.

Yeah.

That's a lot.

It's a lot. Yeah. This was, so I have a quote here from 1862 that I think kind of sets the scene a bit. And it's from an inspector looking over a camp in Washington, D.C. Quote, the atmosphere is impregnated with a malarial odor arising from the decomposition of animal matter just below in an open field where a large number of dead horses are deposited upon the surface and allowed to remain and decompose.

End quote.

Oh, that's so sad.

Brutal.

Yeah. Yeah. I mean, and these huge losses of horses and mules and donkeys, they weren't just a result of Glanders. It was injury, death during battle, just other things. But Glanders greatly impacted both armies during this war. And both sides, of course, blamed the other for introducing the disease. So let's dig into how Glanders became such a problem.

Okay.

It comes down to two basic reasons. How horses were housed and, of course, Glanders itself.

Mm-hmm.

As the war went on and the need for a continuous supply of horses grew, giant depots were built to house thousands of horses together.

Yeah.

They hung out together in corrals. They ate at the same trough. They greeted each other the way that horses do by rubbing noses together because they're social. They're friendly.

Yeah.

They're like smoochy kisses. What's up? Yeah. But these depots created the perfect conditions for Glanders to spread not only within the bounds of the depot, but outside of it. As horses were sent from the depot to the battlefield or to another area they were needed, another depot. The largest depot which is in, I'm probably pronouncing this wrong, Guy's Borough in Washington, D.C., could hold 30,000 horses at once at its peak capacity. Oh, my.

That's a lot of horses.

It's a lot of horses. Imagine how much manure. Tons. That's the first thing that I thought of.

The amount of poop.

So much, so much. And in this large depot, there were no structural really controls for how to prevent the spread of disease. There were stables, so you could house horses there. There was a veterinary hospital that could hold a few thousand if necessary. But horses were only removed or separated after they started showing symptoms of Glanders. And as we know, sometimes the symptoms show up After the horse has already been contagious for a period of time.

Well, and especially because horses can have this kind of chronic, you know, indolent course. Yeah. So it's like, what is the first symptom that someone else actually recognizes? Right. Right. A human has to be able to notice like, hey, this horse is not acting right versus they could have had a wound. They could have had nasal discharge that's going on before you notice necessarily that they're sick.

So. Yep. There's a picture of the depot where you can see hundreds of horses just milling about. You know, they're social creatures. They're hanging out. They're chit-chatting over hay and spreading glanders. And so then there's the glander side of things, right? So there's the fact that some horses can remain chronically infected, but not apparently acutely ill. And so they can spread the infection to a bunch. Glanders is easily spread through contact. And it can last in the soil for, I've read, up to six weeks.

Six weeks, yeah.

And so, yeah, you've got some real problems on your hand. The huge prevalence of Glanders during this time was kind of a big wake-up call in some ways for the veterinary profession where they were like, okay, we, first of all, it's contagious. We see this. Like, finally, yes, everyone's on board. Right.

And this is when the first clinical examination of Glanders was really done systematically, where you were like, okay, this is the prognosis, this is the symptoms, transmissibility, so on and so forth.

Interesting.

But between January 1864, which is when the depot was established, to April 1865, so a year and a few months later, 17,000 horses were lost to disease at this depot. And that means both directly died from infection and destroyed to prevent spread.

Wow.

So for instance, there was one day where I think like over 180 horses died from Glanders. In one day.

In one depot.

In one depot. How many horses died after leaving? How many died after being infected by those horses that were left? How many died that we don't have records for? A lot of the, for instance, in the record to the Confederate Army weren't as complete. Many were destroyed. But they fared possibly even worse than the Union Army. At one Confederate depot, of the 7,000 horses that came through over 15 months, only 1,000 went into the field. The rest died, were shot, or deemed not fit for service. So much life lost.

It's wild.

And if you think about what these numbers meant in terms of the war effort, how are you going to replace this many horses, this many mules, this many donkeys? So the union could actually, they had a better chance of doing this. They could buy horses from Canada. They could buy horses from the out West, the American West.

The South was out of luck. The Confederacy was out of luck. And so I don't think that Glanders has ever said that this is why the whatever, Civil War.

Glanders is how the union won the war.

The right side won. But no, but I do think the loss of life in horses and donkeys was very keenly felt across the board. So war is over. So many thousands and thousands of horses have died. Some are still alive, hanging in there. What do you do with them? You sell them to the public. And you say, hopefully you can help this horse recover on your farm. And in fact, it then spreads to the rest of your farm.

And so Glanders remained a problem for a number of years. But because you were no longer having these huge centralized depots of horses— These outbreaks tended to be much smaller.

Okay, that makes sense.

And so Glanders did not become like a, you know, an outbreak across here, an epidemic across the entire country. It was just like a really unfortunate.

Sporadic cases here and there. Exactly.

But yeah, the field of veterinary medicine would really never be the same after this. It could no longer be argued that Glanders arose spontaneously... due to the phase of the moon or weather or something, contagionism was here to stay. And this also marked the start to the continued involvement of the U.S. government in the livestock industry. Glanders and other diseases were not issues restricted to one farm. They had potentially huge economic costs to the nation as a whole.

And this is something that became ever more relevant as imports of horses and other livestock increased to try to replace all of those animals lost during the war. But Something must have changed, right? Because no one talks about Glanders anymore. So why? What happened?

It's true.

Many things have changed. So the first major advancement happened in 1882 when Loeffler and Schutz isolated and cultured the causative agent of Glanders, which they named Bacillus Maliae. fulfilled all of Koch's postulates. And to put the importance of Glanders into perspective, that was the same year that Robert Koch himself isolated mycobacterium tuberculosis. And so Glanders was up there in terms of like, we got to figure out what this is. Yeah. And like with tuberculosis, the research didn't stop there. Once it was isolated, inspired by Robert Koch developing tuberculin in 1891, researchers came up with something similar for Glanders. They created what they called malion. So this is what you were describing where they drop it

in the horse's eye to be like, at first they thought this will be the treatment, this will be the vaccine, the antitoxin, the cure, just like they thought with tuberculin.

Okay.

Turns out no. And so then they were like, but at least, you know what, it makes for a great diagnostic tool.

Yep, exactly. Interesting.

And so we can screen horses as they come in and other animals as they come in to wherever to then try to prevent. And so with these two things, control of the disease became much more feasible. But all of this research, it came at a huge cost, not to mention the thousands and thousands of lives of horses and donkeys and mules that were lost. Between 1891 and 1892, one year, at least seven European scientists who were working on Glanders died from accidental infection.

Whoa.

Including the two who came up with Malian, Kalnig and Hellman.

Whoa. Jeez.

Yeah. That's depressing. I feel like tularemia is the other one that a lot of scientists working on contracted or died. But while these advancements in the study of Glanders held promise for the future, it really did take a while for this new knowledge to be implemented in a meaningful way to make an impact. And until it was, horses, cats, and people continued to die from Glanders, especially during times of war. The U.S. brought Glanders to Mexico and Cuba.

And the British Army brought Glanders to South Africa during wars in the late 1800s. In the South African War from 1899 to 1902, Glanders was a huge issue. And 326,000 horses, 51,000 mules, and 195,000 oxen died mostly due to disease, including Glanders. Whoa. Yeah. Those numbers are. I know. Shocking. Yeah. Yeah. Of course, Glanders was left behind after the war was over.

Toots.

Eventually, these control measures, you know, especially screening for horses, they did catch up to the infection and cases gradually dropped. So that by the mid-20th century, Glanders had been eliminated from many countries.

Yeah.

Which is kind of remarkable. It is. But in the meantime, a new side of this bacterium had emerged, a weapon of war. Long before Philip and Elizabeth on the Americans got their hands on a sample. Glanders had been used as a potential bioweapon. So in World War I, where horses were still very much used, the infection spread among army horses, as it tended to do during conflicts. But the German army also intentionally tried to use it as a bioweapon. So they tried to contaminate shipments of horses, mules, cattle, and sheep owned by the Allied forces. And I'm not sure how successful it was in that circumstance. But it didn't stop Japanese forces in World War II from deploying it against horses, civilians, and prisoners of war. So now

on to the Americans and the show. So if you haven't seen the episode, what they're trying to do is get a sample of Burkholderia malii to then send back to the USSR to use as a potential bioweapon. And I'm not sure if they even say in the episode specifically what it's for. Is there any truth to any of this at all? It seems possible. So there are reports of the Soviet Union using Burkholderia malii in Afghanistan in the early 1980s, intentionally infecting Mujahideen horses. But I couldn't quite find out if those were confirmed infections or just suspected infections.

Yeah.

But regardless, Glanders is still very much considered to have a strong potential for weaponization. It's deadly. You know, we've talked about this. It's there are limited treatments, and there's antibiotic resistance. And these are the justifications for the US declaring it a tier one select agent in 2000. And putting this into perspective again, what else is on what else is a tier one, you've got smallpox virus, you've got Yersinia pestis, the causative agent for plague, you've got Marburg virus, tularemia, the bacterium that causes tularemia, Ebola virus, anthrax, Nipah virus, and so on. It's, It's a list of notorious deadly pathogens.

Yes.

But that same year that it was declared a Tier 1 select agent in 2000, a 33-year-old microbiologist at USAMRID who was working on Glanders, so this is like the Military Microbiology Research Institute in the U.S., he became infected. The first reported human case in English-language medical literature since 1949. Wow.

According to the case report in the New England Journal of Medicine, he often did not wear gloves. And so that was sort of in the first line, like, admitted to not wearing gloves. But he survived and recovered after six months of treatment. So, Glanders. I mean, definitely one of the deadlier infections that, it might be the deadliest infection that I had never heard of before. doing this podcast.

I think that's valid.

Yeah.

Because when you said it, I was like, I've never heard of it, but sounds great.

I mean, even when we were watching The Americans, I was like, Burkholderia, I know that genus name.

Right. Exactly.

But like, Glanders? But what is Glanders? What the heck? Yeah. And so, yeah. But that's, I mean, that's what I've got. So is there anything new to report since that 2000 case report in the world of Glanders?

Not much, Erin. Probably the best news I have is what you mentioned, Erin, is that this pathogen has been eradicated in large parts of the world, including pretty much all of the EU, Australia, the U.S., North America in general. But it still does cause sporadic disease in horses and donkeys in both northern and southwestern Asia and then into North Africa as well. And there have been cases in parts of South America, specifically in Brazil. So there was an outbreak at the Tehran Zoo in Iran in 2010 that killed four lions and a tiger.

Okay, this was the contaminated horse meat, yeah. Yes, yeah.

Well, actually, at least what I read, they thought that it might have been started by a tiger that was imported from Russia. Oh, interesting. But I don't know. Maybe it was actually contaminated horse meat.

Okay, I might have been reading something else then.

Who knows? There was also the first case reports in Nepal, I believe were conformed in 2022. And then there have been outbreaks in Brazil, mostly associated with animal transportation. So there were 120 cases reported across 43 municipalities between 2020 and 2024. But occasional outbreaks and sporadic cases have also been reported in Iraq, Syria, Bahrain, Afghanistan, Pakistan, India, Mongolia, Turkey.

And that's just in the last like 10 to 15 years. So while we have eliminated this from much of the world, it is certainly not completely gone. It also exists in many labs where people are still researching it and studying it. And despite the fact that per the World Organization of Animal Health or the WHO, this is a reportable disease.

So any single case is supposed to be reported to the World Organization of Animal Health. But it was really, really hard to get hard numbers on these outbreaks. Like exactly how many cases are we having every single year? It was really hard to get like great numbers on that. So that's what I told you is all that I have.

And the elimination in so much of this, so much of the world has happened without any treatment and without a vaccine. Just by these draconian diagnosed early quarantine measures. healthy animals and euthanized animals that show signs of infection or have a positive test, which means that if and when it continues to spread again, we have pretty limited means of control aside from just eliminating these infected animals, which is really depressing. Mm-hmm. In terms of the current research and like how close are we to a vaccine, all that I could see is that things are still just in like early animal studies. So we're not even to say phase one clinical trials. And that's for both an animal or a human vaccine. And I found a

lot more current research on Burkholderia pseudomallei.

Yes.

The causative agent of melioidosis. Yes. which is also a tier one select agent, just like Burkholderia malii, even though the mortality rates for that, which are still terrifying, are between 10 and 40 percent rather than 40 to 90 percent.

That's still pretty dang high.

Still very high. But this is, again, an environmental pathogen whose distribution is across Southeast Asia, Australia, we think probably large parts of Africa and South America. But again, we have not great data on that. as well so that is certainly a future episode that we need to explore definitely but that's what we know about glanders.

Glanders i should have looked into where it got its name.

Yeah i was expecting you to tell me something i assume it's just like glands that's you know my guess swelling glands glanders.

That's my guess but don't know for sure i don't know either citation certainly needed Speaking of, I have a bunch of papers, a lot of which said very similar things, but a kind of a few standouts here that I want to shout out. So there's one by Scherer from 1995 called The Great Glander's Epizootic, 1861 to 1866, A Civil War Legacy. And then by Torres from 2025, Glander's, An Ancient and Emergent Disease with No Vaccine or Treatment on Site.

So, yeah. That was my number one paper, Erin. Okay.

Yeah. It was a great paper.

It was really great.

And then, of course, I want to shout out again the firsthand account by Geiger from 1913, Glanders and Mann. It's really an intriguing read, truly. Yeah.

So that Plasneglectic Tropical Diseases was my number one read. Another one was by Van Zant et al. from 2013. That was called Glanders, An Overview of Infection in Humans. I have a link as well to the case report that you mentioned, Erin, from the New England Journal of Medicine from that case in 2001. But a bunch of other papers, too, about Glanders in animals as well as in humans and a link to the World Organization for Animal Health page on Glanders. You can find all of that on our website, thispodcastwillkillyou.com, under the episodes tab. You can.

You can.

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It does. It does. Until next time, wash your hands.

You filthy animals.

Ep 226 Glanders: Straight from the horse’s mouth

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