This Podcast Will Kill You - Ep 74 Naegleria fowleri: The "brain-eating amoeba"

Episode Date: June 1, 2021

Every summer, when the warm weather rolls around and the local ponds and lakes heat up enough for a tempting dip, remember that there may be something else lurking in those waters besides the people looking to cool off. Naegleria fowleri, the topic of today’s episode, makes its home in warm, fresh waters, and that’s mostly where it stays, until a chance encounter between human and amoeba introduces it to a new locale: the brain. In this episode, we explore the brutal biology of the so-called ‘brain-eating amoeba’, walk through its recent but global history, and discuss the possible future of this pathogen, both good (e.g. treatments, awareness) and bad (e.g. climate change, land-use change). Even though this is a very rare disease, its deadly potential is deeply felt by those impacted by it. We are very grateful to Dr. Sandra Gompf, who shares her story of how her son Philip’s fatal encounter with Naegleria fowleri led her to create Amoeba Season, a Philip T Gompf Memorial Fund for Infectious Disease Research project. You can learn more about Dr. Gompf’s story on her website, amoeba-season.com, where you can also find many helpful links for raising awareness, fact sheets on amoebic meningitis, and a wonderful set of resources for healthcare professionals. As Dr. Gompf says, amoebic meningitis is 99% fatal but 100% preventable, and the best method of prevention is knowledge - Amoeba Season is a great place to start. See omnystudio.com/listener for privacy information.

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I'm Sandy Gumpf. I'm an infectious disease special of Staten faculty with the University of South Florida since 1999. In 2009, our son, Philip, went boating with his family, his aunt and uncle and cousins, on Lake Arenda and Polk County. It's a freshwater lake, spring fed, and they spent the day swimming and tubing and just generally enjoying the day on the water. And about five or six days after he returned, he developed, he came over and during the evening and said that he had a headache, which was kind of unusual for him. And so we checked to see if he had a fever, did he have any other symptoms? We thought maybe he just was a bit dehydrated to summer.

And he seemed like he was okay. He didn't have any neck stiffness. We think about meningitis right away, and that wasn't the case. So we just let him go to bed. By the next morning, he was difficult to wake up. up. And I had gone to work early, and my husband, who's a pediatric hospitalist, went into check on him, and his neck was stiff at that time. He had trouble bending his neck forward. And obviously, that's a warning sign of meningitis. So he rushed him into the hospital

where he works and very quickly had him receive his spinal tap. And shortly after that, he was diagnosed with a very severe meningitis. He had a lot of inflammation. And our assumption was that he had a bacterial infection at the time. The fluid, his spinal fluid was examined for bacteria. They didn't see any. He just had a lot of intense inflammation. the worst inflammation that I have seen.

The type of inflammation that's associated with death. The laboratory did look for amoeba. They didn't see any. And within three days, he began to develop seizures. He was brain dead. So from the time of symptoms, it was about three days. before he was gone. And we had to decide whether to stop life support and donate his orphans, which we at the time, that was a real shock to us. We're physicians who work in the

hospital. We deal with serious infections, serious illnesses, and we see this all the time. We didn't expect it to happen on us, not to ourself. and we couldn't do anything for him. So it was a very helpless feeling. And we assumed, again, that it was just a bad luck, very bad meningitis. And then about six weeks later, we had requested an autopsy as part of donating his organs, and the diagnosis came back with nanglary pary meningitis, amoebic meningitis, which is what's commonly known in the media is brain eating amoevo.

And literally that's what it does. After this happened, you know, it took us a while, took me a while to recover. But one of my mentors are a division director of infectious disease at USF at the time. Dr. John Senate established a memorial fund, the Philip T.Gongf Memorial Fund for education and possibly, research, we thought about what to do with the fund. And we figured the most impact that we could make with the fund is to work on prevention and awareness. Because really, you know, even now,

we have some options for treatment, but it takes really early diagnosis. It takes somebody who knows what they're looking for and knows how to treat it. And it's really, really intensive. And therapy afterwards just for a person to survive. And that's happened in a few cases recently, very fortunately. But it's still the best treatment is still prevention. And it's really easy to prevent. So that's what we've decided to do with the front.

We decided in 2014 to start a campaign, which we call summer as amoeba season, sort of modeling it on the flu season. When it's hot, when it's warm, when people are swimming in lakes and rivers and ponds, and that sort of thing, be aware that there could be a risk of amoebic encephalitis. And we don't want to scare anybody. I mean, this happens rarely. However, when it does happen, it's almost 100% lethal. We say as part of our campaign that it is 99% lethal, but 100% preventable.

A couple of things that we've done with it is a Billboard campaign. And then we also have a social media campaign on Facebook and Instagram. We have wristbands and handouts and postcards and informational materials that we give out as well. We mail those materials to people free of charge, anyone who asks. Probably one of the most, I hate to say it's wonderful, but it's been so positive coming out of two tragedies is that we've partnered with. the Jordan Smelski Foundation for Amigo Awareness, the Smelskies lost their only son from Nygduria Fowleri. He was swimming in Costa Rica in a hot spring-fed pool.

And they have a foundation, and we've partnered with them to continue to offer information to the public, to bring together researchers in Nyglaria Thaleri and parents and the few doctors in the country who were familiar with treating this type of infection. We've helped to develop a best practices treatment regimen using the input from all of these individuals, including the CDC. We're very proud of our work so far. We know there's a lot more to go. There's still, there's so many people that still don't know and so many people that since

our children have. died that have been impacted who themselves and didn't know a thing about it. You know, there's just not enough awareness among even healthcare professionals. So we're still plugging away. We're still trying to advocate for awareness and advocate for parents to try to prevent this from happening. Just to say, the main tools for prevention are either overweighting, you know, activities that will force water up the nose during the summer when you're in fresh water or using

nose clips and anything that really prevents getting water forced up the nose. And, you know, avoiding things like using a netty pot with unboiled water, untreated water. You know, again, just building the awareness or reaching out, you know, monitoring the climate situation and trying to be good advocates for, prevention and education has been our goal. Thank you so much, Dr. Gomp, for taking the time to chat with us and for being willing to share your story on the podcast. We really appreciate it. Yeah, thank you.

Hi, I'm Erin Welsh. And I'm Aaron Alman Updike. And this is, this podcast will kill you. And today is obviously a doozy of an episode. Mm-hmm. Because today we're talking about Nogleria Fowler. which is commonly called the brain-eating amoeba. Yes.

It is, I think, one of our most requested episodes. Yeah, definitely. We've gotten a lot of requests for this. I think it'll be a very interesting one and I think enlightening. Yeah, I think so too. I also had heard of it, but I think only in a very like a sensationalized way, I guess. I mean, the name. And eating amoeba, right?

Right, right. And, you know, with a name like that, I think you assume it's going to be something horrific, but I was not prepared for how terrifying and horrific this disease really is. And just, like, devastating. Yeah. Yeah. Yeah. Well, I guess before we dive into the actual part of the episode, should we do our important business?

Yes. I suppose it's quarantini time, huh? I think we might need one to get through this. Yeah. What are we drinking this week? We're drinking uncharted waters. Yeah. And I think that the name will make more sense as we go into the episode, but basically, spoiler alert,

there's still so much we don't know about this amoeba and about how to control it or prevent it or treat it. and so we're kind of still dealing with like uncharted waters. It's an appropriate name. What's in our drink today, Aaron? It is mescal, ginger ale or ginger beer, and pineapple juice, maybe a little squirt of lime juice. It's pretty simple and it's super tasty, so it's how we like them. Yeah, we'll post the full recipe for our quarantini as well as our non-alcoholic placebo rita on our website. This Podcast Will Kill You.com and all of our social media channels.

and a little bit more business is just that you should go to our website where you can find everything you can ever want to find. We have the sources for all of the episodes that we have ever done. We have all the quarantinis. We have bookshop.org affiliate account. We have Goodreads list. We now have a Patreon. We have a place where you can find all the promo codes that we mentioned.

We have transcripts. I mean, there's probably more. There's a lot. You should check it out. This podcast will kill you.com. There you go. All right. Should we get started? I think we should. We'll take a quick break and then dive in. Dinner shows up every night, whether you're prepared for it or not. And with Blue Apron, you won't need to panic order takeout again. Blue Apron meals are designed by chefs and arrive with pre-portioned ingredients so there's no meal planning and no extra grocery trip. There, assemble and bake meals, take about five minutes of hands-on prep. Just spread the pre-chopped ingredients on a sheet pan, put it in the oven, and that's it.

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quince.com slash this podcast. So, niglaria falari is our pathogen today. Like you said already, Erin, this is an amoeba. I actually didn't realize that it had such a kind of interesting life cycle. I just thought it was just an amoeba. I mean, just saying it's just an amoeba, I'm like, I don't know what that. I don't know what that is or does, really, except I just imagine like, you know, little bloopy edges. That is correct. Little blueby edges.

Sudapods, those are called. And that's how they move around. So this is a free-living amoeba. It lives in freshwater sources, warm freshwater, although it can exist in colder water. We'll get into it. But it exists pretty much across the globe. And I think, Erin, you're going to talk even more about where all we find this. And like some other environmental pathogens that we've kind of talked about on this podcast

before, it has at least one life stage that's very environmentally tolerant, so it can persist even in bad environmental conditions. In this case, that stage is a cyst stage. And so this is the stage that can persist, let's say if a lake freezes over and gets very cold for a period of months, the cyst can persist. A little, yeah, persistent cyst. Yeah, I like that. A little overwintering persistent cysts. or if a small body of water dries out and there's not water, the cyst can persist in dust or dirt. And we've seen this before with other, you know, like fungus that have spores or bacteria like that have spores, etc. So environmental pathogens, not surprising that this guy can withstand harsh conditions.

But then there's also another stage of this amoeba that's actually a flagellate stage, has little flagella. And this is a stage that I didn't know existed of this pathogen, but it's also not really that important to the biology in terms of disease. So that's all I'm going to say about it. It has like an extra, an extra fast swimming stage, but it just doesn't really do much else. I mean, it helps it get food. Yes. From my understanding, which is kind of cool. It just helps it move to a new environment and then it has to go back into the amoeba or trophazoid stage. It's pretty cool, though. It's pretty cool because it also can do that in your body.

Like it's been found flagellates in our CSF, in our cerebral spinal fluid. So it's like moving around. It's like trying to get around to look for food? Presumably, potentially. It's very interesting. Okay. But in general, it's the trophazoid stage or the amoeba. The stage that you think of when you think of the word amoeba.

Yeah. That's the stage that is infective to humans. that's the stage that eats and divides, etc. Okay. So how does one become infected with niglaria falarii? This is an organism that lives in the water. And unlike any other organism that we've talked about so far, the root of transmission is specifically getting water up your nose.

Not by drinking it, not by being exposed to it on other parts of your body, but specifically getting this amoeba up your nose. It's a very specific and interesting mode of transmission because it's very direct. Yeah. What happens is this amoeba, once it's in our nose, penetrates the nasal mucosa, so the mucosa lining up in our nose, and then travels through the cribiform plate, which is the part of your skull, like at the very back, upper part of your nose, in between kind of where your eye sockets start in your skull.

This is a plate, a little piece of bone that has a bunch of holes in it through which the olfactory nerve, your smell nerve that is responsible for allowing you to smell, travels through those holes in your skull, and that's where the nerve fibers come into your nose. So Nigleria phalleri exploits these holes. That's the root of entry that it uses to gain access directly. to our brain. So there are a number of other species of niglaria, but they don't do this. They can't infect humans. They haven't been shown to infect humans. There are some that can infect mice, but it's very interesting, and it is very specific. So nigleria travels along our olfactory

nerves through this cribeform plate directly into our brain. The first place that it invades, unsurprisingly, is the olfactory bulbs, which are like that first part of your brain that they're going to access in that region, kind of right behind your eyes in the front part of your brain. And then from there, once it's in our brain, it's able to divide, grow, eat, continue to live, and spread throughout the entirety of the brain. Literally, it travels throughout the whole brain, invading potentially any and every part of the brain. So what is to stop other pathogens from exploiting those same holes? Right. It's a good question. So we have a lot of barriers, like natural barriers that would

normally prevent pathogens from entering. So your nose is usually full of snot, right? Mewcus. That's our first line of defense against pathogens that would try and enter through our nose. Turns out that niglera phalleri has a number of mucolytics, which are like certain enzymes that are able to break down that mucus. Then they have to not just invade through that mucous, but they actually do have to penetrate through the epithelial cell layers of our nose. Okay. So it's a little bit of a brute force entry. Exactly, right. It's not just like free-form holes in our skull just absolutely open to the world.

Right, right. So it would take something that would bust through those cells. Right. And do so without causing enough of an immune response that our immune system takes care of it before it actually gains entry into our brain. Right. But, well, that's jumping the gun. Okay. Because I was going to say, aren't there people who seem to have been exposed but don't, like, they have antibodies against it?

But they've never had, you know, PAM or whatever? Right. I read a little bit of that. I also read that there have been very few, but a few cases where people have tested, especially children, and found actual amoebas in their nose, but with no infection. And so there are some, there's a school of thought that is perhaps you need to have quite a high infectious dose. And so perhaps that's part of the, you know, sort of spectrum of risk is how much amoeba are you exposed to? And then, yeah, is there something about the immune response as well that's allowed. for only some people to end up becoming infected in others to mount an immune response and not become infected. Right. Yeah. These are all still open-ended questions, Aaron. Uncharted waters.

Uncharted. So once it does gain entry into our brain and is able to spread throughout our brain, it's pretty horrific. It causes something that's called an acute, hemorrhagic, necrotizing meningioencephalitis. That's the kind of most medical of medical descriptions that you can give it. So what it means essentially is that in environmental water sources, where these amoebas are free living, they're feeding on bacteria and things like that. They're engulfing them with their little pseudopods, and that's what they're eating in order to grow and live and continue to divide. In our brain, they're able to do that by engulfing our cells.

they engulf red blood cells, they engulf nerve cells themselves, and various other types of cells that they encounter. So they're causing direct damage to the brain tissue, which causes hemorrhage and bleeding, as well as necrosis, which is just a fancy word for tissue death. And this damage, this direct damage caused by proliferating amoeba, engulfing our cells, unsurprisingly, provokes a pretty massive inflammatory response. Our body goes, this is not okay. And so you have a lot of fluid and a lot of white blood cells that come into that area to try and help and tamp down this infection. The problem is that in the brain, inflammation like that has nowhere to go because our brain is surrounded by our skull, which is rigid and immobile

and doesn't stretch. So this combination of hemorrhage and severe inflammation causes swelling or cerebral edema, and that massive increase in volume of fluid increases the pressure in the brain, which can lead to coma and death because that pressure gets too high and it's pushing on the brain. Yeah. Yeah. It's horrific. So that's kind of the pathophysiology of the disease. If we look at the symptoms of it and what it looks at.

like when someone becomes infected. The disease itself is called primary amoebic meningioencephalitis, which listeners of this podcast I think could figure out a lot from that name. It's obviously caused by the amoeba. That's the amoebic part. And meningioencephalitis tells us that we're dealing with inflammation of the lining of the brain and the brain itself. And the reason it's called primary is to distinguish it from other forms of meningitis that can be caused by amoebas, but other amoebas like entomoeba histolytica, for example, they invade our brain only after travel through the bloodstream, essentially, so they don't go directly to our brain. Right.

So because of this name, we already know a lot of the symptoms because they look a lot like other causes of meningitis or encephalitis that we've actually talked about quite a lot on this show. The difference here is that it's a very, very rapid infection. So usually within anywhere from one to 12 days after infection, average is about five. The symptoms start with a very, very severe headache. And usually one that's unsurprisingly right between the eyes, like a frontal headache. Yeah. With that massive, massive headache, you'll have nausea.

and vomiting, and then often a stiff neck, which is a very classic meningitis sign because of that inflammation. With this particular form of meningitis, you often have loss of sense of smell since your olfactory bulb is very inflamed. But all of these other symptoms are kind of so much bigger that you might not even really notice that necessarily. But then often people will have mental status changes, not sort of just not feeling right, not thinking right, but very quickly will slip into a coma, perhaps having seizures before that. And this disease is almost always fatal. Something like 90, I saw 99% fatal. 97, 99. Yeah. And usually that happens within 7 to 10 days after.

onset of symptoms, often within five days. So this whole course of disease is happening in less than two weeks most of the time. Okay. So there's that incubation period is five days, you said? Yeah, on average. It can be like one to 12 or so, but on average it's about five. And then once onset of symptoms, people usually die within five days as well. And how much variation is there in age groups? Like, does the course of infection, does it, is it, is Is it longer or shorter in certain age groups or? Good question. I didn't look specifically into that.

So in general, in the U.S., especially, the most commonly infected age group are young teenage boys. That's not the case epidemiologically across the globe in other parts of the world. Like in the Indian subcontinent, it's an older age group, but it is still primarily men that are infected. Right. But I don't know if there's a difference in incubation period or symptoms between. age groups, not that I saw, at least in what I read. Okay. It just is, yeah, just exposure patterns for that, yeah, okay.

But you can imagine that for anyone with such a very rapid acute illness, if somebody is misdiagnosed at first with, for example, a bacterial meningitis, which is much more common or a viral meningitis, and started on a treatment for that instead of for primary amoebic menendiocephalitis. then that delay, even a matter of hours, can of course be fatal. But even with prompt identification and treatment, it's still a very, very lent pathogen. What is treatment? Yeah, great question.

There is a, this is a very rare disease. And so there, you know, there haven't been like large clinical studies and things like that. but there is a pretty precise treatment schedule that is recommended based on the few people who have survived with this treatment. So it's a combination of a number of different drugs that are given both IVs and intrathecal, which means directly into the CSF, so usually through like a lumbar puncture. And it's a combination of amphotericin B, which we've talked about a number of times on this podcast.

It's usually an antifungal. but it basically works by disrupting membranes, and so they think that's why it's effective for treatment of this, as well as in combination with another antifungal, one of the azal drugs, either fluconazole or ketoconazole, one of those. And then a couple of different antibiotics, Rifampin, which is often used to treat tuberculosis, as well as meningoccal meningitis,

which is another bacterial form of meningitis. Often also azithromycin, which is another antibiotic, And then a drug called miltifocene, which is an anti-leshmaniasis drug and also a breast cancer treatment, of all things. Did we talk about that drug? I don't know. I don't remember. That name sounds very familiar. Yeah.

It sounded familiar when I read it, but then I was like, I am not good at remembering drug names. Not good for my future career. But yeah, so those and then, that's not the end of the list, it's a very long list, also steroids, dexamethazone, to help with the inflammation, as well as in some cases, people have been treated with something as severe as therapeutic hypothermia where they cool your body down to like 95 Fahrenheit, 35 Celsius or lower to try and help with that swelling in the brain. Or there are other methods to try and reduce that swelling as well. essentially in combination with all of those drugs, keeping track of the pressures in your brain and making sure that you're dealing with any increase in pressure. But even despite all of that, there have been, from everything that I read, there have been five well-documented survival cases that we have good records of.

I saw one paper that said there's maybe up to eight, but some of those didn't, could have maybe not actually been Pam, but might have been a different disease. Gotcha. So I have a question about testing. Mm-hmm. And how do you test for this? Like, obviously you could rule out a bacterial meningitis, but how do you test for this, like, Pam, like one that's caused by niglaria phalitis? but how do you test for this like Pam, like one that's caused by niglaria fowleri? Yeah, yeah, that's a great question.

So there's essentially the same way that you would test for any type of meningitis for the most part. So you diagnose it by lumbar puncture, which is something that if somebody came in with meningitis symptoms, they're going to get a lumbar puncture. The question is just like, are you going to analyze it every single possible way, including looking for amoebas or do you just analyze it in the ways that you might miss the amoebas if they're not live and swimming around. So there's actually on the website that Dr. Gomph mentioned, amoebasseason.com, they have a tab for medical professionals and they had a really great algorithm that they recommend for if somebody

comes in with acute meningitis. And one of the first things is essentially trying to ask someone if there's any history of exposure. So do you have any contact with freshwater sources? Did you go swimming? Did you go rafting? Like have you been in a lake, a river, a stream? Or had contact with well water or groundwater? Have you used a netty pot? Anything that could potentially put contact between your nose and potentially contaminated water sources? And if someone has that history, then you would want to make sure to do the type of test on that lumbar puncture fluid to check for an amoeba. There are also other tests that you can do.

Like there are PCR-based tests and things like that. But lumbar puncture is kind of the standard. So you can see them in the cerebrospinal fluid. Yep. Yeah. Okay. You can see them swimming around. Yeah.

So that's the biology of naglaria fowleri. Okay. Yeah. That was, yeah, horrifying. and scary. It is. It is. It's all of those things. So, Erin, how did it get here? And why are we dealing with something so terrifying? I'll try to answer those questions. But let's take a quick break first. Anyone who works long hours knows the routine. Wash, sanitize, repeat. By the end of the day, your hands feel like they've been through something. That's why O'Keefe's working hands hand cream is such a relief. It's a concentrated hand cream that is specifically designed to relieve extremely dry, cracked hands caused by constant hand washing and harsh conditions. Working hands creates a protective layer on the skin that locks in moisture.

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always on the verge of cracking. It keeps them soft and smooth, no matter how harsh it is outside. We're offering our listeners 15% off their first order of O'Keefs. Just visit O'Keef's company.com slash this podcast and code this podcast at checkout. Texting privacy policy and terms posted at textingterms.us. Texting enrolls you for recurring automated text marketing messages. Message and data rates may apply or apply or place. Stop, opt out. Visit ISSA online for details. Excuse me, what do you do for a living?

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Award-winning adults-only Alaska cruising from Virgin Voyages, Sailing from Seattle. Explore Sailings at Virgin Voyages.com. In 1965, a paper was published in the British Medical Journal, written by Fowler and Carter, two Australian physicians. And in this paper, which is now considered a classic, they described four case studies of meningitis,

all fatal and all originating from a very geographically restricted region, the northern region of the Gulf of St. Vincent in South Australia. Three of the cases were young children, a boy nine years old, and two girls that were eight. All three were in perfect health before they suddenly started to appear lethargic, and then a fever occurred, headaches or throat, stuffy nose. And for each of them, the course of their disease progressed almost the exact same way, with a rapid decline, almost similar day-to-day and no response to antibiotics. And the fourth case described in this paper was that of a 28-year-old man

whose disease progression was a lot longer, but also ultimately fatal. The first case that they described, which was the nine-year-old boy, occurred in 1961, but the other three happened in 1965. All of these individuals were treated as though they had acute bacterial meningitis, and no other causative organism was even suspected, despite the fact that none of them responded to any of the antibiotics administered, and that cerebrospinal fluid samples didn't result in the culturing of any bacterial pathogens. It wasn't until the doctors performed the autopsies that they began to suspect that what they were seeing were not cases of runaway bacterial meningitis,

but something else altogether. Within some of the brain fluid and meningial exudate, they caught a glimpse of unusual small amoebae with extremely high abundance in some areas. It wasn't the fact that they were seeing amoebae in the fluid that was the unusual part. It was the type of amoeba they were. Amoeba infections had been known to happen, like as you mentioned Aaron with the obligate parasitic species, Entomiba histolytica as the primary culprit usually. And infections with this species did occasionally lead to meningitis as a rare, severe complication. But like you said, those cases of meningitis usually arose out of this more systemic infection. And also, if there was an entomiba histolidica

infection, you would pretty much always find it in the gut, at least. But there were no amoeba in the gut of these individuals. And on top of that, the amoeba that the doctors were seeing didn't look at all like entomoeba histolitica. Maybe it was something new. A few years before Fowler and Carter published this article of their case reports, a couple of researchers had demonstrated that free-living amoeba in the genus Acanthamoeba could be pathogenic, at least when they inserted cultures of the amoeba into the noses of mice, which then led to their deaths a few days later. How weird. I know. I know.

Like, why was someone just doing that as an experiment? That's a good question. I probably should have read that paper. Or there are two papers, actually. But Fowler and Carter were aware of these studies, and they cited them in their paper to suggest that the amoebae they were seeing in these four individuals that had died in Australia, that they were likely a pathogenic species of this free-living acanth amoeba. And there was a bit of understandable reluctance to suddenly declare that this group of organisms could pose a threat to human health, since before these mouse studies, free-living

amoebae were not thought to be of any medical interest, really. But, quote, such occasions. Asians are not without precedent, and we consider that the evidence we have points to some species of acanthamiba as a causative agent of acute meningitis in humans. And Fowler and Clark were right, except for one thing. The amoeba that had caused the death of those three kids and that one adult were not a canthamiba, but rather a different species and an entirely separate genus. One that would be given Fowler's name to signify his contribution in bringing this type of meningitis to light. Miglaria, Fowleri. What about the other guy?

You know, I don't know. I don't know why Clark didn't get any cred. He didn't get it. I know. They were probably co-authors. It's not fair. Also, if he was second author and there were just two on the paper, then he was senior author. So, like, it's true. I don't know. I don't know. Is it a post hoc finally getting credit for something? Or, no, I'm just kidding. Maybe there's a non-pathogenic niglaria, Clarki. Clarki. Clarki. Clarki. Yeah, Clarkorai.

So, 1965 marked the beginning of people. recognizing that Nykleria fowleri could be a cause of meningitis in humans, but we know it must have been around before then. And to get a sense of this amoeba's history, I need to talk a bit about the global distribution of this species, which is, in short, like, global, right? It has been found on every continent, except for Antarctica, with infections primarily occurring in subtropical or tropical regions or countries. Basically, the closer to the equator you get, the more cases of this you're going to see.

Although I will say that the distribution is still pretty dang patchy, like very patchy. Very patchy. And that completely makes sense, the warm closer to the equator distribution because the ecology of this amoeba really makes it so that it likes warm things.

I'll get into a little bit of that part later. And Aaron, you asked, when did this get here or how did this get here? And I really wish that I could supply some kind of timeline to the emergence of this pathogenic species and then trace when it spread across the globe. But I couldn't really find any articles describing that. Maybe that's an oversight on my part. Maybe it's just a difficult thing to tease out, partly because like the number of samples from humans is pretty low.

Right. And so it might be difficult to reconstruct this evolutionary history in terms of like a timeline thing. We don't know how fast they evolve maybe. I don't know. What I did learn though is that Nyglaria Fowleri is not the same across the globe and that there are different types within the species

marked by like a base change here or there, whatever. It's not known whether there's a big, amount of variation in like the pathogenicity across these different types. But by looking at genetic analyses of the different types that are present in different parts of the world, we can get a sense at least as to where this species likely originated. And that looks to be North America, where it's thought that Niglaria fowleri evolved from the non-pathogenic free-living amoeba niglaria lovaniansis. Yeah. And that's based on like that, that's So type 1 is present in North America.

A bunch more types are present here. And then it's thought to have spread possibly to Europe and then disperse to Asia and then Australia and New Zealand. Interesting. Yeah. And that's obviously not a complete story. But like I said, we don't have a lot of great data for the different types and prevalence is, especially because you may have noticed that I left out South America and Africa

in that global spread timeline. We just don't have good samples yet, or we're still working on getting good samples. Yeah. Although I didn't see any paper that talked about just how long these amoeba have been infecting humans, I would feel pretty comfortable myself, guessing that it's been a very long time. And that the fact that it was recognized so recently, is causing disease is just a product of like where we were with medical technology and microbiology knowledge at the time. Yeah, definitely, definitely. And like you said, Aaron, the primary sources of exposure are warm pools of fresh water and also like the netty pot thing. And yes, water warmed by electricity power plants may be a relatively recent thing, which is like a place where a lot of

people have gotten infected. Yeah. But natural spas and hot springs, like geothermally warmed water, those have been around forever, as have just like standing pools of warm water, puddles. Puddles, buckets. Yeah. Yeah. And humans have probably always enjoyed a dip in the warmer months to cool down.

And so the genus Nigelaria had been described all the way back in 1899, But like I said, these were not really thought to be of any medical importance. And so they're kind of like overlooked as being able to cause any sort of disease. And it was only in the 1940s that bacterial meningitis could even begin to be treated through the use of antibiotics. Right. And even then you weren't guaranteed success. Right. So it's like before that, of course you weren't, you're not distinguishing your types of meningitis.

Of course not. Right. Right. Exactly. Yeah. And so, yeah, you're trying to treat symptoms rather than cause because it had no tools to treat the cause. Right. And so it's not surprising that these primary amoebic meninoencephalitis cases slipped through the cracks.

It's like that saying when you hear hoofbeats, you think horses, not zebras. Oh my gosh, Erin, I was going to say that later. Really? Yes, it's such a common saying. Well, and I also wrote, I guess which animal you think of probably depends on where you live. Sometimes you may think as debras because whatever. It's a U.S. medicine saying maybe. For sure.

Anyway, so besides me just supposing that it was likely that Nigelia Fowleri caused Pam and humans before those first cases were described in 1965, there's also actual evidence. So once Fowler and Clark's paper came out, it definitely wasn't ignored or forgotten about. It seemed to spark other people around the world to re-examine past meningitis cases that had maybe seemed a bit unusual, or ones where they had seen amoeba floating around in the cerebro spinal fluid, but assumed it was entomoeba histolytica. And that turned up more than a few cases. One of these, which is thought to be the earliest example of Nyglaria Fowleri causing an infection, came from an old specimen in a London pathological museum. This specimen, which had been set aside for re-examination,

before being tossed to make room for, quote, activities more in keeping with a contemporarily scientific approach to medical studies. Oh, interesting. They were basically just like tossing a bunch of stuff, and they were like, we should look at these things again. And one of those things set aside was this preserved brain. from 1909. Whoa.

Yeah. And on this specimen container had the label cancerous dissemination in the lepto meninges, April 1909, a lad of Essex. But reexamination in the 1960s of this brain showed that it wasn't cancer at all, but rather an amoeba that was morphologically identical to niglaria fowleri.

And the pathological findings in the brain also mirrored those more recent cases as well. And there were a handful of other suspected or confirmed Pam cases that preceded the 1965 publication by Fowler and Carter. It was like a possible one in Northern Ireland in 1937. And then like immediately in 1960s, you know, there were some early 1960s in Florida, smattering of cases later on in Texas, Czech Republic, New Zealand, Virginia, and so on.

It really like became here. it is in Australia and then people around the world were like, oh, it's also in my backyard. Oh, it's here. Oh, it's there. As soon as they started looking for it, they found it. Exactly. Yeah. Throughout the 1970s, 1980s, 1990s, cases of primary amoebic meningoencephalitis continued to trickle in. And one of these cases I learned was cared for by my mom.

Nuh. Yeah. So I was talking to her the other day. about how we were doing this episode, and she was like, oh, I'll never forget that patient I had. I was like, mom, what patient? And it turns out that she had a patient with primary mevic menino encephalitis when she was an ICU nurse. This is sometime during the late 1970s or early 80s. Oh, my gosh.

Yeah, this person had gotten it while swimming in some fresh water near Tampa. And unfortunately, the kid didn't make it. And my mom remembers it is just absolutely devastating. She's like, I will never forget it. They tried to fly in medication, but it didn't get there in time. And it was just like horrible. Oh, my God. That's awful.

Yeah. And, you know, that story is like so many others because it doesn't seem as though we've made a whole lot of progress in the treatment arena. But that being said, we have made substantial progress in our understanding of, the amoeba itself, Niglaria Fowleri. It's biology, its pathophysiology, and its ecology. So this history section isn't super long because this is such a newly recognized pathogen of humans, but I do want to go into one more aspect of this amoeba, and that is its ecology and how that plays a role in the number of cases that we see and when we see them. And I know that you're going to talk about current numbers and a bit more in detail about distribution and so on. But one of the

questions I wanted to address in this context of ecology is, is this an emerging parasite? I read that paper too, Aaron. I was just going to say, it's that it's that McIver-At-all paper from 2020. There's like such great info in there. And there's also a beautiful figure of the worldwide distribution of these cases. I was like, oh, perfect. Like, There it is. You can visualize it. But to get at that question of, is this an emerging parasite? We need to think not only about whether numbers are increasing, but if they are, why they might be increasing. Yes. So, first of all, there doesn't seem to be a sharp increase in the U.S. specifically in terms of cases. But it does appear that cases are increasing globally, like overall around the globe.

And it's hard to say whether this increase. actually represents more infections or rather just that like growing awareness of this amoeba is driving the increase, especially in areas like Karachi, Pakistan that are increasingly recognized as hotspots. And so maybe that's that's when you start to shift. You know, when you hear those hoofbeats, you start to think of zebras and not horses, for example. Exactly. Once it once it, once you've seen one, it's also too, I think like your mom would probably think of it anytime that she saw a case because she's seen one before. So anytime you've seen one before, it's going to be something that comes up earlier to your mind. Right, exactly. And so we also know, without a doubt, that this is a very

underreported disease. Right. For example, I saw one number that was for every three Pam cases reported in the U.S., there are likely to be another 13 unreported cases. And with this amount of uncertainty surrounding the numbers of cases, like are these actual cases versus is this just the tip of the iceberg, it's kind of hard to say like what is causing the rise or whether this is on the rise. But that being said, there are a few things that certainly have the potential to increase both prevalence of this amoeba as well as exposure to it. And one of those things is, of course, climate change. Climate change. Climate change. Nigelaria Fowlerai, as we've said, loves warm water.

It's found in fresh water and some brackish water, but not salt water. And some researchers believe that part of the reason it thrives in warmer waters is that those temperatures knock out the competition, like other amoebae. Most cases of Pam happen when exposure is most likely. So the summer months, when people are more likely to be trying to find ways to cool down or the water. is just like happens to be warmer because it's been heated by the sun, et cetera. And a warming climate means warmer waters, not only potentially helping Nyglaria Fowleri to thrive in those places where it's already prevalent, but also allowing it to spread pole wards. This has already been seen with a case in Minnesota, 550 miles north of a previously

reported case. So it was just sort of like isolated out there. And this case, there was no, like, outside travel. And the person had swum in a lake, though, in Minnesota that had been uncharacteristically warm that year. And then another case happened in that same lake two years later. And then these cases, along with another that happened in northern Pennsylvania, have been used as examples of the impacts that climate change is already having on this disease. And it's not just a warming climate that may impact it either. Some areas of the world are predicted to have more drought. And although water exposure is the most common way to pick up this amoeba,

it also appears to be able to breathe in the cyst form of the parasite in dust. I know. I didn't get into that because it's terrifying. Yeah. And it's rare. It's very rare. Yeah, it's definitely, what, less than 10%. Yeah, I think I read about 6% or less of cases that we know of don't seem to have any sort of water exposure.

And so the thought is that it's from dust because the parasite has been found alive and infectious from dust kicked up in the air. Right. But I also like not to not to make this super scary, a lot of the places where it seems to be dust born, there's really poor monitoring. Very poor monitoring. And those are also the places where people have found the amoeba in people's noses without infection. So it's thought that that is a pretty big route. Well, maybe not big, but that is an important route of transmission there. Yeah. Yeah. Yeah. So yeah. So more drought might mean more dust, might mean more insisted Nyglaria Fowleri, more chance for infection. And increasing drought has already led to more people using other ways to store water, like rooftop rainwater. systems or artesian wells, both of which tend to have higher abundances of this amoeba.

In roof harvested rainwater tanks in Australia and South Africa, for instance, Niglaria fowleri is often found in like pretty good numbers. And there's been a lot of great work looking into how different abiotic factors like temperature, pH, salinity, etc., and biotic factors like the presence of predators of Nuglia Fowleri and prey abundance, how these things all affect their abundance and life cycle. But it's kind of difficult to put all of these pieces together. And I think we're still, you know, trying to get a picture of what determines whether or not this amoeba is in this lake versus that lake.

And at this abundance in this lake, is it seasonal? Is it not? Well, and on top of that, how much does abundance in the lake track with infection risk? Because we still don't know that. Like, how many do you need to be exposed to? Like, what is a safe level versus an unsafe level? We don't know that information. Yeah.

No, exactly. But I do think that there's one thing that we do know, and that is that it doesn't seem as though this amoeba is going anywhere, anytime soon. If anything, it seems like we can only expect to see more of it. understanding what drives this patchy distribution of Naglaria Fowleri is super important for estimating and predicting risk, but also getting that information out there is crucial. Yeah. I feel like increasing monitoring, making that information accessible either on signs or in a

public database, like those things seem pretty important in terms of like, you know, having, being armed with the knowledge where you can, you know, understand risk. I suppose. So to be honest, I don't know how much we're doing that here in the U.S. currently. But, Erin, maybe you'll tell me what we're doing about this horrible disease in terms of awareness, control, vaccines, all the things. Well, I'm not going to make any guarantees on any of those, Erin, but we'll take a break and then get into some of it. So nigleria fowleri, primary amoebic menenoencephalitis. It's a very rare disease.

But like you said, Aaron, we absolutely don't have an exact handle on how many cases there are every year. Because not only are there cases inevitably misdiagnosed, assumed to be bacterial or viral, never confirmed to be caused by niglaria fowleri. But inevitably as well, like you said, in many parts of the world, cases are likely never identified because of lack of awareness or because of poor health care infrastructure and inability to test for the disease. But with all those caveats in place, let's talk about what these numbers actually are because there's no definition when we say a rare disease, what does that mean? A review paper, the one that you mentioned, Aaron, that came out in 2020, suggested that there have been a total of 431 cases reported in the literature. Globally. 431 cases from 1965 to now. Mm-hmm.

In the United States, annually, anywhere from zero cases to eight cases are reported. So the average is about three cases every year in the U.S. But across the globe, it's a very uneven distribution, and it's also not uncommon for this to be a disease of outbreaks. There have been a number of large outbreaks that have killed anywhere from 16 to 24 people in one outbreak. And over the last decade, in Pakistan, the number of cases have been increasing dramatically. where, for example, in the United States, from 1968 to 2019, there were 142 cases reported in the U.S. Where in the last decade, 146 cases have been reported in Karachi alone. So this distribution of these 431 cases is not equal.

The vast majority have been diagnosed in the U.S. and Pakistan, and then Australia and a number of other countries. And like you said, Aaron, at least one study that has actually tried to estimate what the difference likely is in reported versus true cases, estimated that while we see documented reported about three cases, that number is likely more like 16. And that was based on epidemiological data as well as like diagnostic codes for unspecified or unidentified meningitis. Okay. And like you said, Aaron, this is an environmentally. transmitted pathogen that could likely continue to increase. Like we don't know how much of this increase is just due to an increase in awareness and reporting, which is a good thing, versus an increase, like a true increase in incidents. But at this point, it is still a very rare

disease. But I want to talk about that a little bit. Because I want to talk about the fact that sometimes I think when we think about something that's very rare, it's easy to kind of brush off. And despite this rarity, this disease has absolutely devastating consequences for individuals and for families when it happens. And the numbers and statistics can only tell us so much about the impact that this disease has. And like just sort of stopping to take a minute to recognize that even though you can say there's only been 400 cases documented across the globe in all these years, those numbers might seem so small. But they're not small to the people that they happen to. And so I think that's one of the reasons why we wanted to do this episode is because even though the numbers might be small, that doesn't mean that they don't have a big consequence. Yeah.

I mean, I think that that goes for like a lot of the diseases that we cover. Yes, I agree. I think it's also very difficult to capture that in numbers, to capture the impact that these diseases have and will continue to have. Yeah. So with that being said, kind of looking forward what's on the horizon, from what I could tell, the vast majority of research that's being done is still in pretty early stages.

So there's a lot of work kind of in vitro studies in, you know, petri dishes, as well as in mouse models, trying to do things like identifying the underlying mechanisms of virulence and investigating a lot of different potential therapeutics. There's a lot of work on that. There's also a lot of work being done to develop better diagnostic tools and detection tools, not just for the clinical setting, but also for environmental detectives. like we talked about. And like you said, Aaron, there's a lot of work that's being done on kind of the environmental side, which I think is really interesting, just looking at like the basic

life history of this amoeba and trying to figure out the more that we know about it, the more that we can potentially use to help treat and prevent this disease. Yeah, it's fascinating. It's a very, because like this is a free living. This isn't an obligate parasite. Right. This has a whole other life. A whole other life that has nothing to do with humans. It does not rely on us. It, I mean, it really is incidental in that way. There's no. There's no drive for this thing to infect humans. Right. And we're not transmitting it on to anyone, you know. Right. It's, yeah. And so I think that a lot of the work, too, is sort of in focusing on prevention as well. So making sure that, especially in areas where the exposure is not necessarily due to recreational water, but is due to water that's used for like nasal cleansing or just cleaning in general, making sure that that water is treated adequately in those places and things like that is also a really important part of prevention. Yeah.

Yeah. Gosh, awareness, awareness, prevention, filtration. It's, yeah. And speaking of prevention and awareness, like Dr. Gompf mentioned, in our first-hand account, she has an awesome website. It's amoeba-sseason.com. There's a lot of great information about my glia fowleri, about prevention, and for health professionals, there's some really great information there about diagnosis,

treatment, all that kind of stuff. So definitely check out that website. And thank you again so much to Dr. Gompf for taking the time to chat with us and sharing your story. Yeah. Thank you. Thank you so much. We really appreciate it. Yeah.

Well, should we do sources? Oh, we should, yeah. I have a lot of sources. I already shouted out one, which was that paper from 2020 titled Is Nigleria Fowleri in Emerging Parasite? And then there are several papers by De Yankier about all about Nygduria Fowleri. I'm pretty sure he's like the leader in the field because the papers were incredibly thorough and informative and very helpful, especially about like the origin and evolution and like the different types and so on. And then there were a lot of other helpful

papers and I will post them all on the website. I also had a few papers. One that I found very comprehensive was called Biology and Pathogenesis of Naglera-Faleri from 2016. And another, if you want to read the actual paper where they estimated, called Estimation of Undiagnosed Noglera-Falleri primary amoebic meningioencephalitis in the United States, that's the one where they estimated the difference between reported and actual cases. As well as a number of others, we post the sources for this episode and every single one of our episodes on our website, this podcast will kill you.com under the episodes tab. Thank you to Bloodmobile for providing the music for this episode, and every single one of our episodes.

And thank you to the Exactly Right Network, of whom we are very proud to be a part. And thank you to you, listeners. We know this was a tough episode. And thank you for sticking with us. Yeah. Well, until next time, wash your hands. You filthy animals.

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