Ep 226 Glanders: Straight from the horse’s mouth

It’s got all the ingredients for a classic TPWKY episode: Deadly zoonotic bacterium (Burkholderia mallei). Tier 1 Select Agent role in war (greatest risk from a bioterrorism perspective). Historically caused devastating outbreaks resulting in mass casualty (of equids). And yet few people know what glanders is (unless you’ve recently watched The Americans tv show). This week, we’re aiming to lift glanders out of obscurity and bring it the attention it so deserves. What exactly is Burkholderia mallei and how does it cause the painful and lingering symptoms it’s known for? When did glanders first strike, and how did it play a role in the US Civil War? Why does it currently rank high up on the list of possible agents of bioterrorism? Tune in to find out all this and more! Support this podcast by shopping our latest sponsor deals and promotions at this link: https://bit.ly/3WwtIAu See omnystudio.com/listener https://omnystudio.com/listener for privacy information.

• 0:01Speaker 00

  This is exactly right.

• 0:06Speaker 01

  Hey, it's Lunchbox from the Bobby Bones Show. Buy smart, drive for less, and trade for more. That's Toyota affordability, and it starts with a great deal on an all-wheel-drive Camry, Corolla Cross, or a Corolla Sedan with the latest features in tech. Or test drive a spacious Grand Highlander or an adventure-ready RAV4. And with so many hybrid models available, you can enjoy longer trips without all the stops, while Toyota's legendary resale value means you could get more at trade-in. Get a deal today and great value tomorrow. Shop toyota.com for deals and details. Toyota, let's go places.

• 0:44Speaker 02

  Morning, Carmen.

• 0:44Speaker 03

  Good morning.

• 0:45Speaker 02

  Quick questions.

• 0:46Speaker 03

  Just one second.

• 0:46Speaker 04

  Sorry. Carmen's worked at this office for 20 years. She knows everything, which is why Carmen has to help with, well, everything.

• 0:54Speaker 02

  Hey, Carmen, what did Faye pitch in 2023?

• 0:56Speaker 05

  Who owns the Nordic account?

• 0:57Speaker 04

  Oh, uh, where's the printer? But Carmen's revenue report is due in five minutes, so she shows them work IQ.

• 1:03Speaker 03

  Hey, Copilot, who owns the Nordic account? And what did we pitch them in 2023?

• 1:09Speaker 04

  Get the context you need with Microsoft Copilot. Work lives on.

• 1:13Speaker 06

  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 3rd 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 4th March, my temperature was 101 degrees Fahrenheit, but I continued to go

• 1:58Speaker 06

  about in the usual way. However, on the 5th, 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.

• 2:41Speaker 06

  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 glanders, 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.

• 3:26Speaker 06

  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 glanders 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.

• 4:08Speaker 06

  The surgeon who remarked that, quote, "Glanders is the most painful disease from which man can suffer," 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.

• 5:36Speaker 02

  I'm sorry. What?

• 5:39Speaker 06

  Right?

• 5:42Speaker 06

  Speechless.

• 5:43Speaker 02

  A hundred percent speechless. Sorry, that was a long inhale of what?

• 5:48Speaker 06

  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. He, part of his arm was amputated because of glanders. And then, so this, this was published, she wrote this up and published it in 1913, and then, two years or three years later, he published a follow-up about his recurrence, where he-

• 6:15Speaker 02

  Because it came back.

• 6:15Speaker 06

  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.

• 6:23Speaker 02

  I can't believe he was alive.

• 6:25Speaker 06

  I know.

• 6:26Speaker 02

  Fascinating, Erin.

• 6:27Speaker 06

  Brutal, just brutal.

• 6:29Speaker 02

  Absolutely horrible.

• 6:30Speaker 06

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

• 6:32Speaker 02

  Only somewhat.

• 6:33Speaker 06

  Only somewhat.

• 6:34Speaker 02

  It only lasted two years.

• 6:36Speaker 06

  Only lasted two years.

• 6:37Speaker 02

  And then had a recurrence.

• 6:38Speaker 06

  Right.

• 6:38Speaker 02

  This was pre-antibiotics.

• 6:40Speaker 06

  Pre-antibiotics.

• 6:41Speaker 02

  Yeah.

• 6:41Speaker 06

  Post-antiseptic technique, pre-antibiotics.

• 6:44Speaker 02

  Pre-antibiotics.

• 6:44Speaker 06

  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.

• 6:56Speaker 02

  Okay.

• 6:56Speaker 06

  Hi, I'm Erin Welsh.

• 6:58Speaker 02

  And I'm Erin Olman Updike.

• 6:59Speaker 06

  And this is This Podcast Will Kill You.

• 7:02Speaker 02

  Welcome to glanders.

• 7:03Speaker 06

  Glanders.

• 7:05Speaker 02

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

• 7:09Speaker 06

  I had never heard of it either, until I was watching The Americans, and the episode was called glanders. I was like, that's weird, and then it turns out-

• 7:17Speaker 02

  What season is that?

• 7:18Speaker 06

  Oh, Erin, let me look it up.

• 7:20Speaker 02

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

• 7:24Speaker 06

  It's such a good show.

• 7:26Speaker 02

  It really is.

• 7:26Speaker 06

  It's really phenomenal. Okay, it's season four, episode one.

• 7:30Speaker 02

  Oh, okay. I probably didn't make it that far.

• 7:32Speaker 06

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

• 7:42Speaker 02

  I love it, okay.

• 7:43Speaker 06

  So.

• 7:44Speaker 02

  Will do, check.

• 7:45Speaker 06

  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?

• 7:57Speaker 02

  Oh, we'll get into all of it.

• 7:59Speaker 06

  Really, really deadly?

• 8:00Speaker 02

  Really, really horrific. I can't wait to tell everyone about it.

• 8:02Speaker 06

  Yeah. And before we can do that, though, it's quarantiney time.

• 8:06Speaker 02

  It's quarantiney time.

• 8:08Speaker 06

  What are we drinking this week, Erin?

• 8:09Speaker 02

  We're drinking Typhoid Mare-y, like, horse. You call it a mare.

• 8:17Speaker 06

  It works well written down.

• 8:19Speaker 02

  It does.

• 8:20Speaker 06

  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. Elliott, about glanders and warfare in North America from 1812 to 1865. And I was like, Typhoid Mary, brilliant. Thank you, love when that happens in a paper.

• 8:37Speaker 02

  Tell us what's in it, Erin.

• 8:39Speaker 06

  Yes, yes, it is an iced chai latte, so oat milk, because maresy-dotes and dozy-dotes and little lamsey-divy, kittley-divy too, wouldn't you? So it's oat milk, it's chai tea, it's maybe maple syrup, maybe honey, whatever you're feeling.

• 8:55Speaker 02

  Yeah, make it a little sweet.

• 8:55Speaker 06

  Extra things, yeah.

• 8:57Speaker 02

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

• 9:09Speaker 06

  Yes, on our website, you can find all sorts of things. You've heard the spiel, check it out.

• 9:14Speaker 02

  I love it.

• 9:15Speaker 06

  Let's get to glanders.

• 9:16Speaker 02

  Okay. We'll take a quick break and dive right in.

• 9:20Speaker 01

  Hey, what's up? This is Kelvin Washington from The Odd Couple with Rob Parker and Kelvin Washington. Buy smart, drive for less, and trade for more. That's Toyota affordability, and it starts with a great deal on off-road-ready Tacoma or half-ton Tundra, two of Toyota's longest-lasting trucks, combining power for work, tech for adventures, and style in between. Built on a reputation for quality and reliability, Toyota trucks are known for holding their value, which could mean big savings when it's time for your next Toyota. So get a great deal today and a great value tomorrow. Shop toyota.com for more. Toyota, let's go places.

• 9:57Speaker 02

  Morning, Carmen.

• 9:58Speaker 03

  Good morning.

• 9:59Speaker 02

  Quick questions.

• 9:59Speaker 03

  Just one second.

• 10:00Speaker 04

  Sorry. Carmen's worked at this office for 20 years. She knows everything, which is why Carmen has to help with, well, everything.

• 10:07Speaker 02

  Hey, Carmen, what did Faye pitch in 2023?

• 10:10Speaker 05

  Who owns the Nordic account?

• 10:11Speaker 04

  Oh, uh, where's the printer? But Carmen's revenue report is due in five minutes, so she shows them work IQ.

• 10:17Speaker 03

  Hey, Copilot, who owns the Nordic account? And what did we pitch them in 2023?

• 10:23Speaker 04

  Get the context you need with Microsoft Copilot. Work lives on.

• 10:58Speaker 02

  So the pathogen that we're talking about today, the causative agent of glanders, is a bacterium called Burkholderia mallei.

• 11:08Speaker 06

  Great.

• 11:09Speaker 02

  Yeah, I pronounced it for you.

• 11:11Speaker 06

  Thank you.

• 11:11Speaker 02

  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.

• 11:48Speaker 06

  Okay.

• 11:48Speaker 02

  Now, there are a couple of other similar related bacterial species that I do want to mention.

• 11:54Speaker 06

  Yeah.

• 11:55Speaker 02

  Because they are perhaps more important or more common causes of disease, especially in humans. And they can be really similar. So one is a bacterial species called Burkholderia pseudomallei, like fake mallei. Love that. And this causes a disease in humans called malleoidosis.

• 12:15Speaker 06

  Yes.

• 12:16Speaker 02

  Very, very similar bug, but the big difference is that pseudomallei can be 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.

• 12:43Speaker 06

  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.

• 12:58Speaker 02

  Yes, so it can live, but it's not replicating.

• 13:00Speaker 06

  It's not replicating, okay, but so.

• 13:02Speaker 02

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

• 13:06Speaker 06

  Okay.

• 13:06Speaker 02

  Yeah, 100%.

• 13:07Speaker 06

  But it makes sense then, given this sort of obligate parasite lifestyle, how it was able to be eliminated from so many places.

• 13:15Speaker 02

  Yes.

• 13:16Speaker 06

  In a relatively short time span.

• 13:18Speaker 02

  Yes.

• 13:19Speaker 06

  Combined with other things, spoilers, but.

• 13:20Speaker 02

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

• 13:36Speaker 06

  Burkholderia, we'll do them all.

• 13:38Speaker 02

  Okay, but today, we're just talking about Burkholderia mallei glanders.

• 13:44Speaker 06

  Glanders and Farsi.

• 13:46Speaker 02

  And Farsi, yeah.

• 13:47Speaker 06

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

• 13:52Speaker 02

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

• 14:02Speaker 06

  Yes.

• 14:03Speaker 02

  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 hosts, first of all.

• 14:46Speaker 02

  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.

• 15:00Speaker 06

  Right, so for instance, unicorns.

• 15:03Speaker 02

  For instance, unicorns.

• 15:04Speaker 06

  I'm wearing a unicorn t-shirt.

• 15:05Speaker 02

  Oh, I was going to say unicorns would just be like a typical host, because those are solopeds.

• 15:11Speaker 06

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

• 15:15Speaker 02

  Oh, this is going to be a fun episode, Erin. I like it. I was going to say, like, carnivores, as an example. Yeah, if they feed on the carcasses of sick animals, lions, other cat species. Sheeps and goats can occasionally get it, but they are relatively resistant. Same thing with cattle, and pigs are apparently quite resistant.

• 15:37Speaker 06

  Why?

• 15:38Speaker 02

  Why? Great question, who knows? I don't know.

• 15:40Speaker 06

  Okay.

• 15:41Speaker 02

  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.

• 16:12Speaker 06

  Okay.

• 16:13Speaker 02

  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.

• 16:54Speaker 06

  What about ingestion?

• 16:56Speaker 02

  Yeah, I mean, in theory, if you get contact with your mouth mucous 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 mucous membranes.

• 17:09Speaker 06

  That's what, so the firsthand account was like, I think it's, I, it was in my alimentary canal, because there were no respiratory lesions that I found.

• 17:18Speaker 02

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

• 17:19Speaker 06

  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, you know, first time for everything, I guess, like, yeah.

• 17:30Speaker 02

  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.

• 17:35Speaker 06

  And what's the infectious dose?

• 17:37Speaker 02

  Oh, great question, no idea.

• 17:39Speaker 06

  Okay, that, yeah, honestly, it makes sense, like, the, the modern day literature on glanders is pretty sparse.

• 17:44Speaker 02

  It is so sparse, Erin, I have so many more questions than answers for this episode.

• 17:51Speaker 02

  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.

• 18:35Speaker 02

  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.

• 19:18Speaker 02

  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.

• 19:36Speaker 06

  Okay.

• 19:37Speaker 02

  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 then eventually to internal organs, which can include the nervous system. And that is often what progresses to fatality in the case of horses.

• 20:20Speaker 06

  Okay, how long is the average disease course?

• 20:23Speaker 02

  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.

• 20:52Speaker 06

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

• 20:59Speaker 02

  The 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.

• 21:25Speaker 06

  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?

• 21:39Speaker 02

  Yeah, that's a great question.

• 21:41Speaker 06

  Okay.

• 21:41Speaker 02

  I think it really depends on what kind of situation these animals are in. Cause 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.

• 22:08Speaker 06

  Okay, so you, 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. What's the case fatality rate?

• 22:32Speaker 02

  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.

• 22:42Speaker 06

  Right.

• 22:43Speaker 02

  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.

• 23:17Speaker 06

  Whoa.

• 23:18Speaker 02

  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.

• 23:27Speaker 06

  Right, yes, it is not treated, it is managed.

• 23:31Speaker 02

  Yes.

• 23:31Speaker 06

  Why is it so, what is it about the bacterium that makes it so resistant to antibiotics?

• 23:36Speaker 02

  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, to treat. It just has like an intrinsic resistance to a lot of different antibiotics. 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. Cause even in humans, it's really, really hard to treat. That's why I'm shocked that our firsthand account survived.

• 24:05Speaker 06

  Yeah.

• 24:06Speaker 02

  In humans, broken skin, so some kind of break in our skin is often a primary route of entry. 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 non-specific 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 non-specific.

• 24:51Speaker 02

  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.

• 25:28Speaker 06

  Good God.

• 25:29Speaker 02

  If on the other hand, exposure is via the respiratory tract, then we can have a really severe pneumonia. 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, 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 non-specific, fevers, chills, body aches for a first few

• 26:13Speaker 02

  days and then improvement and then a relapse.

• 26:18Speaker 06

  Yeah.

• 26:18Speaker 02

  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.

• 26:53Speaker 02

  And even with treatment, mortality estimates are as high as 40 to 50%.

• 27:00Speaker 06

  How did we not know about this?

• 27:02Speaker 02

  I don't know, Erin.

• 27:05Speaker 02

  I really don't.

• 27:06Speaker 06

  So high, over 90% treated, 40 to 50%.

• 27:10Speaker 02

  Correct. But it's again, extremely rare.

• 27:16Speaker 06

  Yeah.

• 27:17Speaker 02

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

• 27:23Speaker 06

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

• 27:35Speaker 02

  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.

• 28:20Speaker 02

  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.

• 28:44Speaker 06

  Yeah.

• 28:44Speaker 02

  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.

• 29:06Speaker 06

  Or aren't enough probiotics in the world?

• 29:08Speaker 02

  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 firsthand 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.

• 29:50Speaker 02

  So it's looking for like a delayed reaction, but they do it in animals' eyes.

• 29:54Speaker 06

  What? I didn't know that.

• 29:55Speaker 02

  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.

• 30:14Speaker 06

  So we have no great treatment. Case fatality rate's still quite high and control is really the only.

• 30:24Speaker 06

  Best course.

• 30:25Speaker 02

  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.

• 30:37Speaker 06

  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.

• 30:46Speaker 02

  Can you make a vaccine?

• 30:47Speaker 06

  And he didn't say this is glanders. He just said, make a vaccine for this specific thing.

• 30:52Speaker 02

  Oh, dear.

• 30:53Speaker 06

  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.

• 31:01Speaker 02

  Yeah, yeah.

• 31:02Speaker 06

  But yeah, I can't believe he survived after hearing all that.

• 31:04Speaker 02

  I cannot believe he survived. I was just like mouth ajar for that whole firsthand, like, what?

• 31:10Speaker 06

  Yeah.

• 31:12Speaker 02

  Yeah, because case fatality rate is really, really high.

• 31:16Speaker 06

  Really high.

• 31:17Speaker 02

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

• 31:22Speaker 06

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

• 31:30Speaker 02

  A hundred percent.

• 31:32Speaker 06

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

• 31:35Speaker 02

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

• 31:53Speaker 06

  How strange.

• 31:54Speaker 02

  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?

• 32:29Speaker 06

  Yeah.

• 32:29Speaker 02

  About this?

• 32:31Speaker 06

  Sure, sure. Can do.

• 32:36Speaker 01

  This is Jason Timp from Hoops Tonight with Jason Timp. Buy smart, drive for less and trade for more. That's Toyota affordability. And it starts with a great deal on an off-road ready Tacoma or half-ton Tundra. Two of Toyota's longest lasting trucks, combining power for work, tech for adventures and style in between. Built on a reputation for quality and reliability, Toyota trucks are known for holding their value, which can mean big savings when it's time for your next Toyota. So get a great deal today and great value tomorrow. Shop toyota.com for more. Toyota, let's go places.

• 33:07Speaker 03

  Morning Carmen. Good morning. Quick question. Just one second.

• 33:10Speaker 04

  Sorry. Carmen's worked at this office for 20 years. She knows everything, which is why Carmen has to help with, well, everything.

• 33:17Speaker 05

  Hey Carmen, what did Faye pitch in 2023? Who owns the Nordic account?

• 33:20Speaker 04

  Oh, uh, where's the printer? But Carmen's revenue report is due in five minutes, so she shows them work IQ.

• 33:27Speaker 03

  Hey co-pilot, who owns the Nordic account? And what did we pitch them in 2023?

• 33:32Speaker 04

  Get the context you need with Microsoft Copilot. Work lives on.

• 34:02Speaker 06

  No one talks about glanders anymore.

• 34:05Speaker 02

  Anymore? No.

• 34:06Speaker 06

  Anymore. Keyword. 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, you know, friends or colleagues or whatever. And this relative obscurity of glanders would come as a straight up shock to veterinarians of the 1800s.

• 34:27Speaker 02

  Wow.

• 34:28Speaker 06

  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. 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 rinder pest, but horses and glanders.

• 35:10Speaker 06

  I mean, why not both, I think, but still, 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.

• 35:33Speaker 02

  I can't wait.

• 35:34Speaker 06

  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. 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.

• 36:19Speaker 06

  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, but doesn't link the two and suggests that only Farsi sores are contagious. But glanders is like a, you know.

• 36:43Speaker 02

  An imbalance type of thing?

• 36:44Speaker 06

  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. And he advised people that is, quote, "As soon as you perceive the least sign of glanders, you must separate the sick horse from all his companions and not suffer him to drink out of the same pail with him."

• 37:08Speaker 02

  Hmm. So knew that it was contagious.

• 37:11Speaker 06

  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's, it's, it is amazing what a chokehold the humoral theory had on science and medicine.

• 37:32Speaker 02

  Yeah.

• 37:33Speaker 06

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

• 37:37Speaker 02

  Right.

• 37:38Speaker 06

  Intense.

• 37:39Speaker 02

  Yeah.

• 37:40Speaker 06

  So for example, in 1817, a veterinary student died of glanders after injuring his hand while performing a dissection on a glandered horse.

• 37:48Speaker 02

  Okay.

• 37:49Speaker 06

  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 cataviric poison.

• 38:05Speaker 02

  What?

• 38:06Speaker 06

  Yeah, like he got sepsis from dissecting the horse.

• 38:09Speaker 02

  I mean, he did, from glanders.

• 38:11Speaker 06

  From glanders.

• 38:13Speaker 02

  The cataviric poison in question was glanders.

• 38:16Speaker 06

  Yeah, but no.

• 38:18Speaker 02

  Wow. Okay. Wow.

• 38:20Speaker 06

  Yeah, yeah. So that was a little bit, I think a few authors were like, that was an unfortunate conclusion.

• 38:25Speaker 02

  That is really quite unfortunate. You were so close and you just missed it entirely.

• 38:30Speaker 06

  What, what? 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, 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.

• 39:14Speaker 02

  Money.

• 39:15Speaker 06

  Money.

• 39:15Speaker 02

  It's always money.

• 39:16Speaker 06

  It's always, I mean, and yeah, horses were an extremely valuable resource. And this was never truer than during times of war. So glanders 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. And horses and, 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.

• 39:56Speaker 02

  What?

• 39:57Speaker 06

  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.

• 40:04Speaker 02

  No, I already have, that's a bad image already.

• 40:07Speaker 06

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

• 40:10Speaker 02

  I believe you.

• 40:11Speaker 06

  But these, 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, you know, 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

• 40:54Speaker 06

  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.

• 41:07Speaker 02

  Wow.

• 41:08Speaker 06

  So they went through that many horses and mules.

• 41:10Speaker 02

  Whoa.

• 41:11Speaker 06

  Yeah.

• 41:12Speaker 02

  That's a lot.

• 41:13Speaker 06

  It's a lot. And 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 DC. 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.

• 41:40Speaker 02

  Oh, that's so sad.

• 41:42Speaker 06

  Brutal, yeah.

• 41:43Speaker 02

  Yeah.

• 41:44Speaker 06

  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.

• 42:04Speaker 02

  Okay.

• 42:05Speaker 06

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

• 42:21Speaker 02

  Yeah.

• 42:22Speaker 06

  Where 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, they...

• 42:32Speaker 02

  Yeah, they're like, "Hi."

• 42:33Speaker 06

  Yeah, they're like, "Hi."

• 42:34Speaker 02

  Smoochy kisses.

• 42:35Speaker 06

  "What's up?" 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, Geisborough in Washington DC, could hold 30,000 horses at once at its peak capacity.

• 43:01Speaker 02

  Oh my, that's a lot of horses.

• 43:04Speaker 06

  It's a lot of horses. Imagine how much manure, tons a day.

• 43:07Speaker 02

  That's the first thing that I thought of. The amount of poop.

• 43:10Speaker 06

  So much, so much. And in this, in this large depot, there were no structural really controls for how to prevent the spread of disease. You know, there were stables, so you could house horses there. There was a veterinary hospital that could hold a few thousand if necessary.

• 43:28Speaker 02

  Okay.

• 43:29Speaker 06

  But horses were only removed or separated after they started showing symptoms of glanders. And as we know, sometimes that, the symptoms, show up after the horse has already been contagious for a period of time.

• 43:43Speaker 02

  Well, and especially because horses can have this kind of chronic, you know, indolent course.

• 43:49Speaker 06

  Exactly.

• 43:50Speaker 02

  So it's like, what is the first symptom that someone else actually recognizes?

• 43:53Speaker 06

  Right.

• 43:54Speaker 02

  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.

• 44:05Speaker 06

  Yep. There's, 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 they don't, 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.

• 44:36Speaker 02

  Six weeks, yeah.

• 44:37Speaker 06

  And so, um, yeah, you've, 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, that's like, finally, yes, everyone's on board. 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.

• 45:10Speaker 02

  Interesting.

• 45:11Speaker 06

  But between January 1864 and, uh, 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.

• 45:22Speaker 02

  Whoa.

• 45:23Speaker 06

  At this depot. And that means both directly died from infection and destroyed to prevent spread.

• 45:28Speaker 02

  Wow.

• 45:29Speaker 06

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

• 45:35Speaker 02

  In one depot.

• 45:36Speaker 06

  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 records of 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.

• 46:00Speaker 02

  Ah.

• 46:01Speaker 06

  The rest died, were shot, or deemed not fit for service.

• 46:04Speaker 02

  Ah.

• 46:05Speaker 06

  So much life lost.

• 46:08Speaker 02

  Yeah.

• 46:09Speaker 06

  It's wild.

• 46:10Speaker 02

  Oof.

• 46:11Speaker 06

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

• 46:39Speaker 02

  Glanders is how the Union won the war.

• 46:41Speaker 06

  The right side won. But no, I, 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 this, 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, these outbreaks tended to be much smaller.

• 47:20Speaker 02

  Okay.

• 47:21Speaker 06

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

• 47:29Speaker 02

  Sporadic cases here and there.

• 47:31Speaker 06

  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 US 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.

• 48:11Speaker 02

  Right.

• 48:12Speaker 06

  So why? What, what happened? Uh, it's true, many things have changed. So the first major advancement happened in 1882, when Loffler and Schutz isolated and cultured the causative agent of glanders, which they named Bacillus mallei, 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.

• 48:41Speaker 02

  Yeah.

• 48:42Speaker 06

  And like with tuberculosis, the research didn't stop there. Once it was isolated, inspired by, uh, Robert Koch developing Tuberculin in 1891, researchers came up with something similar for glanders. They created what they called mallein. 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.

• 49:09Speaker 02

  Okay.

• 49:10Speaker 06

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

• 49:14Speaker 02

  Yep, exactly.

• 49:15Speaker 06

  And so we can screen horses as they come in, and other animals as they come in, uh, to wherever, to then try to prevent. And so with these two things, control of the disease became much more feasible.

• 49:27Speaker 02

  Okay.

• 49:28Speaker 06

  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.

• 49:47Speaker 02

  Whoa.

• 49:48Speaker 06

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

• 49:52Speaker 02

  Whoa.

• 49:53Speaker 06

  Yeah.

• 49:54Speaker 02

  Geez.

• 49:55Speaker 06

  Yeah.

• 49:56Speaker 02

  That's depressing.

• 49:57Speaker 06

  It's like, I feel like tularemia is the other one that a lot of scientists working on contracted or died.

• 50:02Speaker 02

  Ended up dying from.

• 50:03Speaker 06

  Yeah. 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. So, and until it was, horses, cats, and people continued to die from glanders, especially during times of war. The US brought glanders to Mexico and Cuba, and the British Army brought glanders to South Africa during wars in the late 1800s. In the, 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.

• 50:46Speaker 02

  Whoa.

• 50:48Speaker 06

  Yeah.

• 50:49Speaker 02

  Those numbers are.

• 50:50Speaker 06

  I know. Shocking.

• 50:53Speaker 02

  Yeah.

• 50:54Speaker 06

  Yeah. Of course, glanders was left behind after the war was over.

• 51:00Speaker 02

  Toots.

• 51:01Speaker 06

  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.

• 51:13Speaker 02

  Yeah.

• 51:14Speaker 06

  Which is kind of remarkable.

• 51:15Speaker 02

  It is.

• 51:16Speaker 06

  But in the meantime, a new side of this bacterium had emerged. A weapon of war.

• 51:24Speaker 06

  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 in the show.

• 52:04Speaker 06

  So if you haven't seen the episode, what they're trying to do is get a sample of Burkholderia mallei to then send back to the USSR to use as a potential bioweapon in, well, 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 mallei 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.

• 52:50Speaker 06

  It's deadly, you know, we've talked about this, it's deadly. It can infect both humans and animals. There are limited treatments, and there's antibiotic resistance. And these are the justifications for the US declaring it a Tier 1 Select Agent in 2000. And putting this into perspective again, what else is a Tier 1? 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, nepevirus, and so on. It's a list of notorious.

• 53:24Speaker 02

  Yep.

• 53:24Speaker 06

  Deadly pathogens.

• 53:25Speaker 02

  Yes.

• 53:27Speaker 06

  But that same year that it was declared a Tier 1 Select Agent in 2000, a 33-year-old microbiologist at USAMRED, who was working on glanders, so this is like the Military Microbiology Research Institute in the US, he became infected. The first reported human case in English-language medical literature since 1949. 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.

• 53:57Speaker 02

  Yeah.

• 53:57Speaker 06

  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.

• 54:14Speaker 02

  I think that's valid. Yeah. Because when you said it, I was like, I've never heard of it, but it sounds great.

• 54:19Speaker 06

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

• 54:24Speaker 02

  Right, exactly.

• 54:25Speaker 06

  But like glanders?

• 54:26Speaker 02

  But what is glanders?

• 54:27Speaker 06

  What the heck?

• 54:27Speaker 02

  Yeah.

• 54:28Speaker 06

  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?

• 54:37Speaker 02

  Not much, Erin.

• 55:12Speaker 02

  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 US, 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.

• 55:48Speaker 06

  Okay, this was the contaminated horse meat, yeah.

• 55:51Speaker 02

  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.

• 55:56Speaker 06

  Oh, interesting.

• 55:57Speaker 02

  But I don't know, maybe it was actually contaminated horse meat.

• 56:00Speaker 06

  Okay, I might have been reading something else then.

• 56:02Speaker 02

  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.

• 56:45Speaker 02

  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, 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 diagnose early, quarantine, healthy animals, and euthanize animals that

• 57:30Speaker 02

  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. 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 1 clinical trials. And that's for both an animal or a human vaccine. And I found a lot more current research on Burkholderia pseudomallei.

• 58:03Speaker 06

  Yes.

• 58:04Speaker 02

  The causative agent of melioidosis.

• 58:06Speaker 06

  Yeah.

• 58:07Speaker 02

  Which is also a Tier 1 Select Agent, just like Burkholderia mallei, even though the mortality rates for that, which are still terrifying, are between 10 and 40% rather than 40 to 90%.

• 58:18Speaker 06

  So pretty dang high.

• 58:19Speaker 02

  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.

• 58:39Speaker 06

  Definitely.

• 58:40Speaker 02

  But that's what we know about glanders.

• 58:43Speaker 06

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

• 58:47Speaker 02

  Yeah. I was expecting you to tell me something. I assume it's just like glands.

• 58:51Speaker 06

  That's my guess.

• 58:53Speaker 02

  Lymph node swelling, glands, glanders.

• 58:55Speaker 06

  That's my guess, but don't know for sure.

• 58:59Speaker 02

  I don't know either.

• 58:59Speaker 06

  Citation certainly needed.

• 59:01Speaker 02

  Speaking of. Speaking of.

• 59:05Speaker 06

  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 Sharer from 1995 called "The Great Glanders Epizootic, 1861 to 1866: A Civil War Legacy." And then by Torres from 2025, "Glanders: An Ancient and Emergent Disease With No Vaccine Or Treatment On Sight." So, yeah.

• 59:33Speaker 02

  That was my number one paper, Erin.

• 59:35Speaker 06

  Okay, yeah, it was a great paper.

• 59:37Speaker 02

  It was really great.

• 59:38Speaker 06

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

• 59:48Speaker 02

  Yeah, so that plus neglected tropical diseases was my, like, 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.

• 1:00:20Speaker 06

  You can. Thank you to Blood Mobile for providing the music for this episode and all of our episodes.

• 1:00:27Speaker 02

  Thank you to Leanna and Tom and Mark and Pete and everyone else at Exactly Right for everything that you do to make this podcast possible.

• 1:00:35Speaker 06

  Thank you, thank you. And thanks to you, listeners, watchers, anyone who participates in this podcast. We appreciate it. You are the reason we do this, so thank you, thank you.

• 1:00:45Speaker 02

  Yeah, thank you. And thank you, as always, to our patrons for your support over on Patreon. It really does mean the world to us.

• 1:00:51Speaker 06

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

• 1:00:54Speaker 02

  You filthy animals.

• 1:01:23Speaker 07

  Hey, it's Lunchbox from the Bobby Bones Show. Buy smart, drive for less, and trade for more. That's Toyota affordability, and it starts with a great deal on an all-wheel-drive Camry, Corolla Cross, or a Corolla Sedan with the latest features in tech. Or test drive a spacious Grand Highlander or an adventure-ready RAV4. And with so many hybrid models available, you can enjoy longer trips without all the stops. While Toyota's legendary resale value means you could get more at trade-in. Get a deal today and great value tomorrow. Shop toyota.com for deals and details. Toyota, let's go places.

• 1:02:01Speaker 04

  With ChatGPT, you can do more than get answers. You can get things done. Whether you're leading a big project, planning an elaborate trip, or trying to balance work and life, ChatGPT can help. Give it a goal, plus things like files, notes, or project plans, develop a trip itinerary with daily updates, or create a prioritized schedule. So you can spend less energy sorting out the details and more on bringing your biggest ideas to life. Get started at chatgpt.com.