Ep 188 Candida yeast: Here, there, and everywhere

This is exactly right. Let me take you back to when I was a weird, nerdy 14 year old. I'd recently started menstruating and was incredibly self-conscious about managing my periods at school. The popular girls would congregate in the school bathroom so they'd hear the unzipping of my bag and the crinkle as I unwrap sanitary products from their packaging. I was terrified about what gossip would be spread around school if people found out that I was on my period. I made the decision to avoid changing my sanitary products at school. This created a lovely warm moist environment for yeast so it's no surprise that I got a yeast infection or thrash. If you have not had the pleasure, it's like an infected horsefly bite. It's an incessant itch that is constantly screaming for attention. I couldn't sleep, it hurt to pee. I couldn't concentrate on anything except for the pain of the itch. This, coupled with being a teenager, with hormones coursing through my body, the shame and self-loathing of my poor decision made this a really distressing time. To add to my humiliation, I had to tell my GP about my symptoms, but I let the polite vernacular to do so. I eventually stammered that I had an itch at the front of my bum and the GP took pity on me and my mum was able to take over the consultation. I was asked no further questions and no invasive tests were performed. I was given a prescription for canister and this was the first time I had ever used a pessary and had no idea whether I was inserting it correctly. However, I recovered and became scrupulous about my vaginal health and changed my sensory products at least every four hours as recommended. Fast forward, about 10 years, I'm in a sexual relationship and I get the itch. I assume it's thrush and get canister over the counter at the pharmacy and then carry on with my day. The thrush clears up for a while, but then it comes back. So I call the GP and they tell me to go to the sexual health clinic. To do this, I have to take annual leave to travel there in the opening hours. Even then, they only accommodate walk-ins. So I may not have been seen. If these barriers are not enough, I was also extremely embarrassed with the whole idea of going to a sexual health clinic. Eventually, I saw a GP who gave me a swap and confirmed I did have recurrent thrush. My partner at the time laughed and told me that thrush was no big deal, which is probably because he couldn't catch it. Because my first was recurrent, the GP gave me a blood test for diabetes, which came back negative. There was no obvious cause, so I fell through the cracks a little bit. The GP had never asked about my environment. If they had, we probably would have figured out the cause pretty quickly. In the office, my desk was positioned directly underneath the aircon, and I really feel the cold. So the office administrator had very kindly given me a little heater to put underneath my desk. I liked to have it snuggle between my knees, which created a really lovely warm environment for myself and also for the East. At the time, I didn't put two and two together. I just carried on in discomfort for the next few months with the added expense of Caniston on my regular shopping list. There were other knock-on effects, my sleep suffered, my relationship suffered. My partner at the time really struggled with the reduction of intimacy. So on the nights when saying no wasn't worth the drama, I would grab my legs, close my eyes, and think of England as the saying goes. For those who haven't had the pleasure, it feels like having sandpaper shoved inside that Hawksfly bite I described earlier. Several years later, I'm happily single. I work from home and can control my environment, and I am thrush-free. I found thrush to be extremely isolating, and I hope that if anyone can relate to my story that they find comfort that they are not alone. Thank you very much for listening. I feel like that story really exemplifies some of the shame that's surrounding things like yeast infections. Yeah. I feel like no one wants to talk about yeast infections. I was going to say literally every person with a vagina has had a yeast infection. 75% actually. Almost everyone. That is pretty much close to everyone. Yeah. Yeah. Thank you so much for sharing your story with us and everyone listening. We really appreciate it. Yeah. Thank you. Thank you. Hi, I'm Erin Welsh. And I'm Erin Almond Updike. And this is, This Podcast Will Kill You. Welcome to Yeast Infections. And I mean, yeast infections- It's broader. Yeah. Well, I feel like, but it's all yeast or yeast-like. And so it's, yeah. Candida. Yeah. And not just Candida Albicans. Candida, Oris, Candida. All the Candida's. Those are the only two I know right now, at this point in our conversation. I can't believe we haven't done this. I can. Our list is simply too long. Oh, that was good. No, it wasn't. Our list is long. And you know, we're doing it now. That's all we can say. We're doing it now. I learned a lot. We're about to learn some more. And we're about to tell you about a recipe for our quarantine. Or placebo read it today. Plessy, yeah. Actually, you can make it a quarantine if you want. Sure. It's called a Candida. The Candid Shot. Yeah. The Candid Shot or just a Candid Shot? Well, the only reason I was thinking a Candid Shot is because Candida, and then what happens to that A, we just move it over. But the Candid Shot also works. Your grammar. I like it. I mean, I can't do shot. A Candid Shot is fairly simple. It is like rose, soda and rhubarb. I was going to say like you just stand there and someone takes your picture. That wouldn't be candid. No, you were right. Anyways, you can find the whole very complicated recipe for that Plessy Burrida. And if you want to add alcohol, a quarantine on our website, this podcast.com and our socials. Are you following us on socials? Aaron's making videos of these drinks. Poor videos. Yeah. Not very good, but they exist. We're trying. We're trying. Instagram, TikTok, Facebook, website. This podcast will kill you.com. Check it out. Transcripts, links to merch, links to bookshop.org. Affiliate account links to GoodreadsList, links to music by Bloodmobile, the sources for each and every one of our episodes. There's also embedded YouTube videos there. So if you check out our... Oh, you've been doing that? Aaron, look at you. Sometimes I'm a little bit late because I have to wait for the day that they publish. It doesn't matter. They're there. And some other things. A Contact Us form. Thank you, everyone, who has submitted your story for our first hand account using our first hand account form. Just know it could be years before we contact you, but we read them all. But we do read them all. Yeah. Yeah. Yeah. Yeah. I think that's it. That's it. You did a great job. Thank you. Do you want to hear about the biology of Canada? Of course I do. Let's take a break and get into it. So the star of today's show is a fungus. And as we've learned in previous fungal episodes, fungi tend to be a little bit complicated. They do. Yeah. They really do. And in the case of Canada, often people cite it as a yeast, right? We think yeast infection. And a yeast is a single-celled fungus, right? Right. Like the kind of yeast that you use for bread. But Canada also exists as a filamentous mold with its little hyphae or sometimes pseudo-hyphae branching out. Okay. So it's really quite multifaceted. And it might not be surprising that in part because of that, Canada can cause a really wide range of potential infections, not just vaginal yeast infections. There are several different species of Canada that cause infections in humans, the most common of which is Canada albicans. But there are, I think there's a push to group all of the other ones as like non-albicans, Canada. Or non- yeah, NAC. N-A-C-Y. Non-Albicans, Canada yeast. Anyways. And these actually, some of them have been growing in abundance and posing a growing concern to infectious disease specialists and in public health officials and infection preventionists in hospitals. Well, because that's what I was wondering. So why would you, like, are all non-albicans, Canada as pathogenic, like equally pathogenic and problematic? All of them tend to be more apt to resistance, which is one of the big concerns about them. Yeah. Very interesting. Yeah. So the kind of most notable ones, and there are more than these two, but kind of the most notable ones are Canada auris, and we'll talk more about that later. And then what used to be called Canada glabrada, but what is now has been reclassified as NACA seomyces glabratis. Okay. And I think that's also part of why they're saying call everything non-albicans, because it's like they've been renaming some things, which is important, but also gets confusing. Yeah. Yeah. And then also Canada parasilosis. So that's the other one. Sure. And all of three of these do tend to have more resistance to antifungals than Canada albicans. And so we'll talk a little bit more about them a little bit, and you can ask questions, and I might not have the answers. But for most of this episode, especially for the, like, pathogenicity part of things, I'm going to focus on Canada albicans. It is by far the most common, something like 90% of us are colonized right now as we speak on our skin or in our mouths or in our vaginas or in our guts, because it can live there too. So Canada is or causes what we often call an opportunistic infection, meaning that when the opportunity arises, it will cause infection. And when it does not arise, it simply co-exists with us. And maybe even beneficial. Maybe, though I didn't research that at all. That's okay. I have a paper. Love it. And it lives not just on our skin and in our mucous membranes, but also in the environment, and mostly just hangs out there a little bit unobtrusive until it becomes a problem. I think of it as just getting too big for its britches and deciding to take over the place, writing executive orders, and all of the judges and other lawmakers are nowhere to be found. Can't keep it in check. Just kidding. I guess this is fine for me to take over. No one's here. Yeah, no one else is here. I'll just move in. So let's talk about what kinds of problems it can cause, because it's really varied and not all Canada infections are created equal. There are broadly two big categories of Canada infections. There's mucocutaneous infections, so skin and mucous membranes. And then there are systemic infections. You can probably guess which one is more severe. The most, I don't even know if this is, I don't know if it's true to say the most common, but probably like the thing that I certainly I think about and that most people probably think about with Canada is a vaginal infection or vulva vaginal candidiasis. And we kind of said this already, but something like 75% of people with a vagina will have candidiasis at least once in our lives. 6% to 10% of us may have recurrent vulva vaginal candidiasis, which is usually defined in the literature as more than four per year with resolution of the symptoms in between each episode. Okay, not just like persistent. Right. Like so, I mean, okay, that is the chronic part. Are there, how long, oh, okay, never mind. Am I getting ahead of things already? Yeah, you're asking a lot of questions. I'm like, how long does a yeast infection last? How long does treatment, how long does it take to resolve things? How long do, does it ever self-resolve? Yeah, certainly can, certainly can self-resolve. How long it lasts just totally depends on the person and their immune system and what kind of treatment they get if they get treatment. Treatment depends on the situation. It can be topical. So sometimes we use like vaginal suppositories or vaginal creams or it can be oral. And that's usually a shorter course unless it's a more resistant strain or you have recurrence or something like that, then sometimes you need a prolonged course of oral antifungals. Okay, real quick one question. Okay. So for the people who have recurrent yeast infections, what is driving that recurrence? Isn't that a great question? We don't know. We don't know. Okay. Yeah. What I can tell you a little bit about since I haven't even mentioned it yet is what the symptoms of a vaginal yeast infection are. Sorry. I just got excited. I love it, Erin. Don't ever apologize. For your excitement. But again, most of us is probably... For other things, yes. Most of us have probably experienced this. We can see inflammation. We see a white, chunky, cheesy kind of cottage cheese discharge, itching, burning, pain. And this is an infection that is very easy for people to dismiss. And by people, I mean the people not experiencing it. But it has a substantial economic and morbidity burden. And we'll talk a little bit more about that later on in this episode. The risk factors for why do people get yeast infections and some people don't, or when does someone get a yeast infection. Risk factors can include poorly controlled diabetes. Sometimes we see associations with sexual activity, but it's not considered by any means a sexually transmitted infection because again, this is like a commensal. Right. We also can see an increase in cases with increased estrogen states. So like during pregnancy and things. But by far the most common is antibiotic use. And that's true for a lot of candle to infections, not just vulva vaginal infections. But it's not just the vagina. Our other mucus membranes can often get infected. So we can see oral or esophageal candidiasis, which at least in the US, we often call thrush. And I think that they call thrush like a variety of candle infections in other countries too. But that is when you get infection of the tongue, the oral mucosa, the gingivus, or your gums, or your throat, or esophagus. And you usually will see this kind of off white, yellowish. It can almost be like almost so dark that it looks kind of brownish or blackish, just depending on like how long it's been there and things. But this plaque that forms in the mouth or in the throat, most of the time with these infections, we see them with some type of immunocompromising condition. So something like HIV AIDS or chronic steroid use, including, yes, inhaled corticosteroids, if you're not rinsing your mouth. And that's why you're supposed to rinse your mouth after you use like a inhaler. Interesting. Okay. Okay. Or conditions that cause like a reduction in saliva, which is going to help to wash out the yeast that's in your mouth and keep it moving. What would that, what reduces saliva? Oh, something like Sjogren's syndrome, which is quite rare. But then there's other things that, I don't know, other specific conditions where people might have less saliva or people who wear dentures, I think too, are at higher risk of oral candidiasis. Okay. But we can also see it on our skin or in our nails. We can get into Trigo. So like in the skin folds, maybe say axilla groin diaper rash for babies. You can get it on the penis. We call that balanitis. You can also get it on the nails. So either with like an ingrown nail. So we call that perinica or onicomycosis, which is like the nail infection. Is that like on top of your nail or under your nail? Or like, how does that happen? It's like within the nail itself. Within the nail itself. Yeah. Okay. Okay. Yeah. It's here, it's there, it's everywhere. So given the right set of circumstances, it can absolutely flourish. And sometimes it can really go too far and cause a systemic or invasive infection inside of our bodies. The most common and most serious of these invasive, candidial infections is called Candidemia, which is a bloodstream infection. So yeast growing in our bloodstream. And this has a mortality rate of 30 to 40% depending on how you calculate it. And that's today. And that's in high income countries. And that's with all the treatments available. Exactly. Yep. Yep. Wow. And part of that is because of just how hard it is to diagnose and treat these infections, especially once they've gotten into our bloodstream, but also because the vast majority of people who end up with a bloodstream infection are very sick to begin with. So we see this really commonly in things like ICU's when people are already, you know, their immune systems are kind of at their limit. And things like that. Once someone has an invasive, candidial infection, they can end up with a number of other places that this Candida infects thereafter. So you can get an infection in the eye and it can cause Candida endophthalmitis, which can potentially cause permanent blindness. It can go into the heart and cause endocarditis, so infection of the heart and the valves of the heart. Okay. It can get into the central nervous system and we see this commonly in premature newborns, something like 15 to 20% of the time, if a preemie ends up with invasive Candidaeusis, it will end up in their central nervous system. So with amenindritis or encephalitis, I know. And then especially after surgeries or other like abdominal procedures, people can get abdominal Candidaeusis and that can result in like a fungal abscess or can sometimes infect the liver or the spleen. And in those cases can sometimes cause a really prolonged infection that's really hard to treat. Do we have a more granular answer as to how this happens then there's a breakdown immunosuppression and things just sort of spill over? It's a good question, not a super more granular one than that. Okay. There's always, I mean, almost always there's going to be some, I say almost just a hedge, but realistically there's always going to be some kind of like precipitating events, right? Whether it's some other infection, whether it's a bone marrow transplant, a solid organ transplant, you're on immunosuppressive drugs, you have HIV AIDS, you're born with an immunodeficiency, so many potential conditions that lead someone to be more susceptible. And then it's like those right set of circumstances. The other thing that's very commonly predisposed to someone to an invasive infection, especially a bloodstream infection, would be having indwelling lines. So if you have ports, if you have catheters, as we'll see, Canada forms biofilms very easily. And so they can colonize and form a biofilm on those indwelling lines and then put you at risk for invasive infection because it's just bopping off little yeasties from the biofilm. I feel like, so on this podcast, we have talked about a few other opportunistic pathogens that tend to just hang out and then crop up when something is a little bit out of balance. There's dysbiosis, whatever. Do we know why Canada rather than Staph aureus or why Canada rather than strep? What is that deciding factor? I don't think it's always an either or. Sure, of course not. But yeah, I don't know. It's a good question. And it could be any of those. So it might just depend on that individual. What is their skin more colonized with? What do they happen to have on their bodies? What other antibiotics are they being exposed to? What happens to gain that foothold to begin with? Because our immune systems respond to bacteria and to fungi in different ways, so what type of immunocompromising condition do you have? And does it leave you more susceptible to fungus because your immune system is just not as good at getting at that fungus versus a bacteria or something like that? Are you already on all the antibiotics possible? And so you've killed all those and now only the yeast are left. And as a fungus, Canada is already in some ways kind of harder for us to fight off compared to some bacteria because it's a eukaryote, right? So it's a little bit closer to us. So it's harder for us to have antifungals. It's harder for our body to recognize it sometimes. However, Canada is also special and has quite a number of virulence factors that facilitate its ability to infect us and cause disease. For one thing, it can do that switching thing that I mentioned at the top. It can exist as a yeast or as this filamentous hyphae form, depending on its environment. And this allows it to disseminate widely when it's a yeast, right? It's really hardy. It can exist in the environment. It can be between people. And then it allows it to invade through our epithelial barriers when it's in its hyphae form. And then that also allows it to evade a lot of our immune responses. Okay. So the hyphae form does impact our immune, like its immunogenicity or something detection. Majorly, majorly. And so it's really the hyphae form that we tend to see that ends up being the reason that we have invasive disease. And so are all Canada albicans individual, cells or whatever, capable of this transformation? As far as I know, yes. And there are differences. And it does seem like the switching part of it is what makes them so good at causing disease. Because when you breed strains that are only hyphae or only yeast, they're not quite as good. But in general, they all can do both. They're quite adept like that. Canada also has a bunch of proteins that we call adhesions, which I feel like we've talked about this who knows on what episode. But they're basically sticky proteins that allow it to make these biofilms and to colonize places like our skin and mucus membranes, and also things like catheters, pick lines, like all of these lines that especially if someone is already ill and in the ICU, they usually have quite a lot of lines. And a biofilm, for anyone who's forgotten the glory that is biofilms, they're these really complex assortments of a bunch of different microorganisms that end up forming their own protective barrier, this little extracellular matrix that completely blocks our immune response from accessing them, which means that they can continue budding off these little yeasties or having their little filamentous forms just kind of creep out and go invade deeper into our bloodstream, for example. Where did we, was it Legionnaires' disease where we talked a lot about biofilms? Definitely talked about them. Yeah, but something since then too, because that was a long time ago, but I can't remember what it was. Someone else, do you remember? Probably have a better memory than us. But lastly, they also have a bunch of enzymes that they can secret these, this fungus, to help break down our endothelial cell barriers and damage our cells and hide from our immune system. And what's so fascinating is that part of the way that Canada does this is actually by recognizing some of our metabolic cues. So they're sensing what's going on in their environment, aka in our bodies and changing the way that they grow, changing the structure of their own cell wall, they are just really, really well adapted to our human bodies. And probably the two biggest challenges when it comes to dealing with candidul infections, especially the severe ones, but even, you know, muco-cutaneous infections, which I'm not saying those are not severe, just in comparison to bloodstream infections, it's diagnosis and treatment. And the diagnosis of Canada is really challenging in part because the gold standard is to grow it in culture. And these grow really slowly. They take a really long time to grow in culture. And our culture methods are imperfect. So if you have, say, a low abundance, you might get negative cultures, even though you have plenty of yeast growing in your body. Well, and then how do we, because it's a commensal, and it's on, you said, over 90% of people, how do we know whether detection of Canada is a problem or like regular growth or overgrowth? Great question. So yeah, you can have false positives and false negatives both directions, right? Depending on exactly what site you took it from, depending on how you took the samples. In general, though, it does not belong in our blood. So if Canada is growing from a blood sample, yeah, but you're right, if it's from like a skin sample, is it overgrowth or is it not? And some of that comes down to like clinical diagnosis as well, too. What do things look like and stuff like that? What are your symptoms? Are you experiencing discomfort? Yeah, exactly. There are PCR methods and things, but they're not always available. And then treatment is hard, in part because of the toxicity of a lot of drugs that we use, and because of increasing antifungal resistance. Yeah. Yeah. Yeah. That's it. I could talk a little bit more about the details of the treatment, but it's a little bit boring and niche. Well, maybe there are times when I talk about treatment in the history, and so maybe then we can figure out if there are some... There you go. If you have questions. If there are gaps. Yeah. So tell me, Erin, about the history of this little fungus, won't you? I will. I will. Modern Society. I simply love when episodes start like this, Erin. I just love it. Keep going. Honestly, sometimes I write this and then I read it over and I'm like, why did you write this? And it's too late now. Here we are. Because it's great. That's why. Keep going. Modern Society is blamed for a whole host of diseases and disorders. Depression and other mental health disorders, certain kinds of cardiovascular disease, metabolic dysfunctions, even allergies and asthma to some extent. This is not a novel concept. The Industrial Revolution in the 19th century sparked intense discussion over how things like long working hours and stress, poor nutrition, lack of sunshine and education for women contributed to the rise in these nervous disorders like neurasthenia or hysteria. Yeah. Setting aside the problems with some of those diagnoses, especially neurasthenia and hysteria, and whether their relationship with modernity can truly be described as causal, I think that this idea of diseases of modernity captures a reality that we sometimes struggle with. And that is that progress comes at a cost. Most of the costs that people are concerned with are general or hard to quantify, just as like a feeling that we have. So for example, our computers are capable of more than we could have dreamed of. And at the same time, we are more sedentary and overconnected than we have been in, you know, for most of human history, contributing to chronic and mental health conditions. Have things improved overall thanks to computers? Are computers a net positive? Absolutely. Like there's no doubt about that. But we can also consider the cost factored into that equation. 100%. Yeah. And I think that we are especially prone to thinking that science and medicine moves in one direction, more knowledge, more treatments and cures, better healthcare when it's not being thwarted by uninformed disinformation spreaders like RFK Jr. and his ilk. But unfortunately, this forward progress, it's not always the case, or at least there's a more nuanced story to tell. Sometimes it's more of like a two steps forward, one step back kind of a thing. And rarely are we able to predict what that backwards step might look like. This was certainly the case with antibiotics. And no, I'm not talking about antibiotic resistance. I mean, people did that is a step back and people did see the writing on the wall almost immediately when they came out. But I mean, Canada. Oh my gosh, I love this. Yeah. When penicillin came onto the scene in the 1940s, quickly followed by other antibiotics, such as streptomycin in the 1950s, they led to a revolution in healthcare. It's a powerful story that we all know well. And if you don't, you should check out our antibiotics episodes from years back. But the miraculous recovery of patients on the verge of death from a bacterial infection, that's just one of the transformations brought about by the advent of these drugs. The other was Canada changed from a mostly benign, which is not to say it wasn't uncomfortable or caused issues, superficial fungal infection to a sometimes invasive systemic disease. And ultimately, it led to a few fringe doctors promoting an unsupported hypothesis that to this day is used to sell people snake oil supplements that can harm much more than they can heal. Oh, I'm so shocked to hear that. I got so like just frustrated with this episode anyway. I bet. And that part of it. But before we can tell the story of that transformation, let's first go back in time to the early history of candidiasis. Okay. Of course, it's Hippocrates. Like it's always Hippocrates. Honestly, I was going to get a little sad if there wasn't because I was like, gosh, is this only going to be a modern thing? But like, no, it must have been around forever. It's been around for it's been around forever. Yeah. Forever. Yeah. Yeah. It's our friend. It lives with us. Yeah. Yeah. Yeah. Sometimes it's like, you know, a little not even codependent, but just like dependent and we're like, we need to stop. Stop calling me. Stop calling me. It's too much. Do not disturb mode. Just like, yeah. Yeah. Okay. Hippocrates. In one of his classic texts, he describes Thrush. Like oral Thrush is what I'm referring to, particularly in people who are already sick or in poor health. Galen also made mention of Thrush, especially in sick kids. And there's a smattering of mentions throughout the 1600s and 1700s where Thrush, Thrush really is what predominates throughout history. And that's understandable because yeah. Yeah. Because it would have been there and no one was going to talk about vaginas. Of course not. Yeah. No. But it was actually Thrush was recognized as relatively common in newborns and apparently so common in France that in 1786, a medical society offered a reward for its study. Oh, interesting. Yeah. Outbreaks of Thrush were known to happen at lying in hospitals where people came to give birth and then spend some time in recovery afterwards. And so there would be like outbreaks throughout the hospital. And in the 1800s is when the many faces of Candidiasis or Candida began to be noted. Esophageal, vaginal. So the first vaginal yeast infection was clinically described in 1849. It's so late. And published in the Lancet. Yeah. Wow. Okay. Okay. Mouth lesions, brain lesions even, intestinal disease, even some systemic infections. But disentangling what caused these infections was much more challenging, especially when this yeast can overgrow or cause infections on so many different parts on the body, in the body, everywhere. Or when there are like moral or ethical considerations like doctors were reluctant to examine women. And even when a doctor did conduct an exam and found a yeast infection, they were like, oh, it's just a symptom of another disease. It's not a condition in its own right. Yeah. Oh, that's so interesting. Okay. I mean, but similarly oral thrush, you know, you talked about how it can almost be like brown. It was recognized or thought to be the precursor to diphtheria in a lot of cases because that thick membrane as well. Yeah. Okay. And in some cases, the infectious nature of these lesions was suspected or like couldn't really be ignored. It was like, well, it has to be infectious. And in other times, it was, the infectious nature was proven by experimental infections, one of which at least one of which led to an infant's death. Oh, my God. Healthy infant. Let's just infect a bunch of these with this and see what happens and one died. Isn't that absolutely horrific? That's horrible. Yeah. This was in the 1800s. 1800s. Yeah. Oh, God. Yep. And, you know, I think that around this time, when germ theory rose to prominence, it reinforced this idea of one microbe, one disease, one cause, one disease kind of a thing where one pathogen was responsible for one infection in particular, which is great for diagnosis and developing treatments or vaccines. But at the same time, it made it harder for people to realize or recognize when something didn't fit that paradigm, such as Canada, which by this time, let's say by the early 1900s went by a million different names. And so for the full picture of what Canada was capable of, we needed someone who was able to look past the trees to see the entire forest. And that someone turned out to be Rhoda Benham, who later became a leader in the emerging field of medical mycology. In a 1931 article in the Journal of Infectious Diseases, she put forth the idea that all of these diverse infections, from mouth to vaginal to intestinal, all of these different things, each of which had been attributed to different fungal species with different names, because they were like, oh, we isolated this from the mouth. Oh, this came from the fingernail. It must be this different thing. It actually just came from one species, one organism, which at the time was manila albicans, later turned into Canada albicans, which also, did you know, means whitening white? Like it's like, I did not. White, white. White, white. I mean, does tend to have white, cheesy, miss. Exactly. She wrote, quote, if one were ignorant of the source of these cultures, one would be unable to distinguish, for example, M. albicans isolated from thrush, from M. celosis isolated from sprue, and it would seem necessary for the present to regard such forms as merely strains of one species. And quote. There you go. She said other words like, just look at it. They're all the same. It's all the same. Stop calling these things different names. It's the same thing. It's the same thing. Yeah. Which was a pretty like novel idea, I think, for like the concept that this thing could be cause infections in such diverse, basically everywhere in the body, it seemed like. It's a new idea. And so at this point, let's say the 1930s or so, Canada had caught the interest of a few researchers. But to be honest, it was more of an afterthought, like not super pressing. It was like, there were a lot of other things that people were concerned with at the time. It wasn't the hottest thing. But the birth of the antibiotic era was about to change all that. By the 1950s, antibiotics had saved countless lives around the world. But the excitement that had accompanied the emergence of this new class of drugs was beginning to be tempered by a few unexpected consequences. New antibiotic resistant strains causing infections that couldn't be treated, allergic reactions, toxic side effects and some of these and a rise in Canada infections, both superficial and invasive in those receiving antibiotics. And this last observation led the Council on Pharmacy and Chemistry of the American Medical Association to release a statement in June of 1951 that said that bottles of the three leading antibiotics should carry the following warning, quote, patients receiving these drugs may be more susceptible to monilial or other yeast like organisms, end quote. Wow. Yeah. Way back when. Way back when. And it's interesting. This is this was not without controversy. Right. Because first of all, it was hard, I think, for people to draw the connection between how were, how exactly were antibiotics causing this greater susceptibility? And secondly, since Canada is a commensal of humans, how do you distinguish between what is a harmless or a harmful overgrowth? Right. And thirdly, what are we supposed to do about it? Right. Right. At that time. At the time. 1951, no treatment. Okay. But within a few years, that last question, what do we do about it, would be answered 1954 with the first antifungal on the market, niastatin, which is the market name Mycostatin. This is developed by Elizabeth Hazen and Rachel Brown a few years before. I think it was like in production. And then by 1954, it was on the market. Okay. Most of the antibiotics then available were derived from fungal species like penicillin, which had used these compounds to compete with bacteria. Like I feel like, yeah, it's, it's, I just love, yeah. And so using that same logic, niastatin was developed from a bacterium, streptomyces norsii, found in soil from a friend's garden, like one of their friends garden. And because Hazen and Brown reasoned that soil was this battleground for all sorts of microbes that are all like, let's bring out the big guns. You know what, we're gonna, here's this compound for this and this compound for that. And I'm gonna out compete you and I'm gonna just destroy you. You're gonna think ecologically. I love it. Ecology matters. And so that's, yeah, voila. There you go. Nice satin. And then, but the other two questions, sort of like, when is Canada a problem? And what, why is it doing this? Those proved a little bit more challenging to answer. Clinical evidence was mounting that while antibiotics were associated with systemic and deadly infections with Canada through disrupting the microbiome, these weren't as common as initially thought. And it might actually have been a combination of our detection methods improving for this. And so that being partially responsible for the apparent rise, both in systemic as well as superficial. And by superficial, I mean like, on your skin, exactly infections. But the important lesson was that antibiotics could disrupt someone's microbiome, which provided Canada an opportunity to grow more than it ordinarily would. And that disruption could happen from other things besides antibiotics. Like for most people, any yeast infection would be handled relatively simply through an antifungal like nice statin, and then some of the later ones that came onto the scene. But for some, such as those who are immunocompromised, that microbial dysbiosis, regardless of whether it was triggered by antibiotics or not, could result in more invasive and difficult to treat infections. And Canada ended up around this time, let's say the 1970s and 80s, being labeled a, quote, unquote, a disease of the diseased, which is like not maybe the nicest way to put it. It's not the best way to put it. But I think what it does is it conveys that this was an infection of disruption, something that would become even more clear in the 1970s and 80s in these decades with more patients than ICU use, you know, as healthcare and our ability to help people improved overall. We had more people who were, you know, alive in a hospital. People alive even as they got sicker. And that comes with its own set of problems and complications. And then things like organ transplant. Also, you know, people who were on immunosuppressive drugs to prevent rejection, organ transplant was a very relatively, very new thing, not just relatively new. And so, and then in, especially in the 1980s, the rise of the HIV AIDS pandemic. And candidiasis, you touched on this a bit, but it was especially a problem for people with HIV AIDS. And one estimate suggested that by the mid 1980s, 75% of people with AIDS had oral candidiasis. And that, of course, had the potential to become more invasive because their immune systems were so suppressed. And fortunately, by that time, there were newer antifungal drugs that had come on the scene that were usually quite effective in treating these infections. And their development was in part motivated by the spread of this yeast. But the increase in awareness that Canada received during this time, it also inspired a different movement. One not entirely grounded in scientific evidence. Okay. In 1982 and 1983, two books came out claiming that Canada was the cause of a host of poorly understood and ill-defined physical and mental health issues. Okay. One book was titled The Missing Diagnosis by Orian Truss. And the other was The Yeast Connection, a medical breakthrough by William Crook. Okay. Literally, Dr. Crook. Okay. I can't believe it. I can't believe it. I mean, I guess you don't have control over that, but. You don't. Yeah, it just is, it just was funny to me. Yeah. And the overall premise of both of these books were that many people were unknowingly living with a chronic overgrowth of Canada, which led to an overall more immunosuppressive state and predisposed them to a variety of conditions, ranging from tissue injury and mucosal infections to mental health issues. A self-diagnosis checklist was included along with a nine-step program with also many sub-steps for treating this alleged overgrowth. Okay. Diagnosis was confirmed only with a positive response from the nine-step program. What were the nine steps? Were they like, eat healthy and exercise? Basically. Basically. Will make you feel better? Yes. Exercise was one of them. Okay. As the diet was another. Okay. Here we go. I found it. Continuing observation in order that concomitant diseases can be detected accurately diagnosed and specifically treated. Exercise program. Okay. Mental health program. Okay. Avoidance of chemical pollutants. Okay. Maybe there's more information in the book on that. What does that mean? Do not know. Okay. The use of antioxidants. Okay. Use of special laboratory tests, like the ratio of helper cells to suppressor cells. Okay. Blood vitamin studies, mineral studies in hair, blood and urine, amino acid studies in urine, essential fatty acid profile. That's step six. Right? Okay. Okay. Special dietary program. We'll get into that in a second. Including supplements. That was one on here. Of course. That you can only get from them. Yep. The use of antifungal agents for months. Okay. Topically and orally. The use of allergenic extracts of candida albicans for immunotherapy or provocation neutralization. Okay. That's, yeah, that is, that's nine. Okay. Yeah. Okay, Erin. So, so you do all these things at once so you have no idea what's helping. You do all these things at once. Right. Right. As far as I can tell, it's not a stepwise thing. Okay. Cool. Yeah. Okay. So just to give you a better sense of like the picture of this, I'm going to quote from Truss's missing diagnosis. Okay. This is just, this is just excerpted. There's a lot more where this comes from. Okay. Quote. Depression is common, often associated with difficulty in memory, reasoning and concentration. These symptoms are especially severe in women who in addition have great difficulty with the explosive irritability, crying and loss of self-confidence that are so characteristic of abnormal function of the ovarian hormones. Poor end-organ response to these sex hormones is confirmed by the common association of acne, impairment or total loss of libido and the whole range of abnormalities of menstrual bleeding and cramps as well as a very high incidence of endometriosis in those who have undergone hysterectomy. Many of these patients also start developing multiple intolerances to foods and chemicals, making it increasingly difficult for them to live in a normal environment. Many or all of these intolerances disappear as the yeast problem is brought under control. End quote. What? Yeah. Okay. So yeah, bringing it under control, I went through the nine steps there. It's a lot of it's that long term, not just antifungals though. Also, antibacterials were prescribed like antibiotics. What? Yeah. Okay. Canada extracts that one for immunotherapy and this anti-candidate diet. So there's a lot to unpack here. So first, there's the vague and diverse array of symptoms of what was termed candidiasis hypersensitivity syndrome. Okay. And then women being called out in particular because of something about like sex hormones, it was unclear to me from that, what the connection was. What any of that meant? Yeah. And like, why does that have anything to do with Canada? Canada. Okay. Birth control was also blamed. Of course. Birth control has been blamed pretty commonly. Yeah. Like realistically, even if you're on an estrogen-containing birth control, you're probably having lower estrogen levels on average than you would if you were, well, certainly if you were pregnant, but also then if you were like cycling. And so there isn't really a good association between, there is a slight association between like menopausal hormone therapy and a slight increase in yeast infections, but even that is not like major. Right. And also we're talking about yeast infections. Right. Vaginal yeast infections. Not. Whatever this is. Yeah. Yeah. Yeah. And I like the other symptoms are like when I said earlier that like, these are really vague in general, it's things like headache and malaise. So things that people do experience probably regularly in association with who knows what many different things. I mean, it just definitely feels like this is something that's preying on people who haven't found an answer from somewhere else. Literally, that's what I have down here. Yeah. We'll get there. But I want to tell you about the diet too, because like, I think that this is still incredibly, incredibly popular. So the diet requires strict adherence and is incredibly limiting. So there's no sugar at all, even fruit, like you can't have fruit. Oh my God. Okay. No pork, no gluten, no popcorn, coffee, nuts, mushrooms, truffles, no alcohol. Many grains are excluded, but fresh and organic meats and fish, but again, no pork are allowed. Why no pork? Something about pork, allegedly, according to this, pork contains some sort of retroviruses that. What? Yeah. Yeah. Like that retroviral something. I'm not like pro-poimette. I love bacon, but I know it's terrible for me, but like, it's not causing Canada. It's not. It's not. And these books though, and the idea that they promoted became wildly popular, like selling out book prints or whatever, and leading many people to seek months of systemic and topical antifungals from their doctor. They discontinued birth control and they started to take a suite of supplements that were probably not great. Actually, there have been a few cases of people who either go on the diet or start taking these supplements that end up putting them in a hospital. Oh, geez. Or they're on these antifungals for so long. So it got to a point, it got to be such a problem that by 1986 or in 1986, the Executive Committee of the American Academy of Allergy and Immunology released a statement listing their critique of the Candidiasis Hypersensitivity Syndrome. And I'll link to this because it has like almost like a point by point refutation. And their ultimate conclusion was that, quote, on the basis of the evidence so far reviewed and until appropriate published evidence to the contrary is brought to its attention, the practice standards committee recommends that the concept of the Candidiasis Hypersensitivity Syndrome is unproven. And quote. I mean, pretty straight forward. It didn't really do anything. Over the next decade, though, researchers like started to look into this with carefully designed clinical trials because they're like, if this is the thing, this is, we have a path forward, right? Let's figure out. Let's figure it out. So we can treat it well. They tested the anti-Canada diet. There was a test or a trial with prolonged treatment with Nystatin and also looking, screaming for Candida throughout the body. No strong evidence emerged for the condition. And if you look at Candidiasis Hypersensitivity Syndrome on Google Scholar, you will find a few papers from the 80s and early 90s. But anything that's more recent tends to come from things like the Candida Clinic or like the Candida, whatever sort of Candida Pro, right, Pro this idea. They're clearly like they have an angle because they're trying to sell you a supplement or something. Yeah, a book. Yeah. But and in fact, because one of the ideas that they promote is that, okay, you need to like, and why the diet is there is that it cuts down Candida in your gut. And there's actually a paper from 2022 that suggests that Candida in your gut is a mutualistic beneficial back to your beneficial organism. And it's a sign of it can be a sign of a healthy gut. I mean, you want your gut microbiome to be quite varied. Yes, you do. You do. But yeah, nevertheless, this persisted. This idea of Candida overgrowth or Candidiasis Hypersensitivity Syndrome, and you've got countless organizations, supplement companies, and forums dedicated to spreading the word. And why it has remained so popular, I think, comes down to two main things. And the first is that is what you touched on. Medicine doesn't have all the answers. And people seeking help are sometimes dismissed or have their questions ignored and their concerns ignored. And I don't doubt that people who think they have this condition or are experiencing symptoms of Candidiasis overgrowth or Candida overgrowth are probably experiencing uncomfortable, disruptive, or even debilitating symptoms. But so far, no evidence points towards Candida as the culprit. Doesn't mean that someone isn't having headaches or digestive issues, but that it's probably not Candida. Right. And the Candida diet probably helps because you're paying attention to what you're eating. You're cutting out a lot of things that probably don't make you feel great. Right. It would be great if we could all cut out sugar. Yes, probably. I mean, yeah, there are some great if we focus. At least tone it down a bit or like some elements, but like not yeah. Although not fruit. Not fruit. Yeah. Please. I eat so much, so many blueberries. I know that about you. Yeah, it's one of my absolute favorites. I mean, it's why I love Costco. Just just for the blueberries. Everything else. Clanshells. Yeah, fistfuls of blueberries. But but again, these, just because you're receiving a benefit or feel better from the Candida diet doesn't mean that your Candida levels are changing. In fact, there have been studies that indicate that there is no change. And honestly, it would be great if it were Candida. Wouldn't that be nice? Because there'd be here's here's the straightforward answer. There's probably a straightforward fix. Right. This is what we can do. People who are desperate for answers, desperate for relief may find themselves looking outside of medicine for someone to tell them what's happening, which brings me to the second reason why I think this has remained so so popular. It's because there are countless people who are happy, more than willing to profit off of it. There was once I just I googled anti-Candida supplements just to see what was out there. And it's like endless options, of course. And I just I am I'm so livid, like livid isn't even the right word. I'm just so exhausted by the fact that this is a thing that is continuing to grow and grow and grow. There was one supplement business, and I won't name the name of it, but it popped up as one of the companies when that's selling these anti-Candida supplements. And I looked up, okay, what is their net worth? What is their income? What do they get every year? Tens of millions of dollars every year for medicine backed quote unquote, absolutely not medicine backed cleanses that promise to restore gut health or make you free from Candida. I mean, it all just makes me want to do a whole other supplements episode because there's still so much more there. It's even like when we did that what last year? Yeah, was that last year already? It's worse. It's worse. It's growing and growing and growing. There are also I've been looking at this a lot. There are so many because you said these, a lot of these people who promoted this idea back in the 80s were physicians. Oh, so is the person who has the supplement. Right. That is what is on the social medias right now, which I won't call out my name, but like almost every very prominent, even physician, influencer, or whatever sells at least one supplement or has advertised for at least one supplement or whatever. And it just makes it like, it makes it so, so, so hard because you just can't. And it's not like we said in our supplements episode. It's not like supplements are evil. It's not like they're all bad. It's just that they're completely unregulated and so many of them are profiting off of mis and disinformation. I mean, yeah, in terms of the morality question, I feel like it is pretty immoral to manipulate people and put fear into them to sell, to make money, to make yourself richer. A hundred percent. But I just meant like we do use supplements themselves. Sure. In men's for things. Yes. Yes. And it, we're painting with a broad brush here, but I think that like when we're talking about someone who's taking a supplement to reduce their candida levels, absolutely. There's no evidence. There's no evidence. Yes. It's all, it's all, yeah. It's predatory, predatory garbage. So, yes. And then I think the other issue with the, sorry, I didn't really mean to get this like upset about things, but I got you into it. So keep coming. But there's, you know, I was also looking up, I was just curious because especially yeast infections, I have heard so many different home remedies and you've got people who are like, put a clove of raw garlic cut in half, tie it around a string, just coat it in yogurt, coat, just like shove a bunch of yogurt up your vagina. That'll get rid of it. A jade egg or whatever. You know, like, I'm sure that there's something on that website that we, yeah, yeah, disapprove of. But all of these things, like they're misguided and it is, oh, it just, it reveals so much of what is wrong with expertise, medicine, people being missed by medicine. Yeah. And like our limited capacity to answer all these questions, probiotics, do they work? Maybe, maybe not. Maybe not. That question, we cannot answer right now. What is even in a probiotic, right? Which bacteria matter in what quantities, which don't matter. Each person is unique, their microbiome is unique. I mean, we don't even have like, you know, thinking about this in like an actual puzzle and you know, you always put the edge pieces together first. Like we're still flipping over pieces. Like we're not even close to having that. That's so true. That's so true. We don't even know how many puzzle pieces we're dealing with. Absolutely not. Could it be a 1000 piece puzzle or like a 100,000? Yeah. That's so true. I think that, yeah, I think that the fact that the anti, the anti-candidate diet and these alternative approaches to treating yeast infections, just as an example, the, as, are as prominent as they are, I think speaks to the failure of medicine to adequately meet people's needs, the disgusting greed and lack of regulation that allows people to sell snake oil on the basis of fear and lies. And also, I think it shows the very human tendency to want answers, to want to take action. And Erin, I, I'm sure that, you know, things have improved or maybe there's reason to hope. Good news on the horizon. Sorry to end this so depressingly. Oh, that's okay. I don't know that what I'm going to say is going to be any less depressing, but we can get into what the landscape of Canada is like today. Let's do it. Okay. So when it comes to, I'll start with invasive candidiasis, because that's obviously the most severe forms of candidiasis. We're talking systemic infections. A Nature Reviews Disease Primers from 2024 reported an estimated community-wide incidence rate. So if you're just looking at general population, you might think it's not that bad. It's around four cases per 100,000 people in high-income countries. Oh, not that bad. But you would be wrong if you thought of it that way, because this is not a disorder, systemic invasive candidiasis that is particularly prevalent amongst the general population. Right. But in hospitalized patients worldwide, we see about a hundred cases per 100,000 hospital admissions. And in the ICU, an estimated five to seven cases per 1,000 ICU admissions. In newborn babies, especially premature newborn babies, we see 12 cases of invasive candidiasis per 100,000 births of premature babies in the U.S. Wow. So this is a disorder, a disease that for most people who are listening or walking around, like on your commute to work, if you're hearing this, you might think it's not that common. But if you work in a hospital, if you're unlucky enough to end up sick in the ICU, this is a very serious and seriously common problem. And with the rise of other strains of Canada, like Canada oris, which was first found only in 2009, it's a very, very new, newly identified pathogen. Yeah. This is a species that was first identified in Japan. And since 2009 has been found in more than 30 countries, it spreads really rapidly through hospital settings. And it really rapidly gains resistance. A lot of times this, the different strains of C. aurus have resistance to begin with, but then it picks up new resistance. So we see pan resistance, we see resistance in C. aurus, some strains to almost all of the antifungals that we use. And it's been in the U.S. since at least 2013. And according to the CDC in 2023, there were 4,514 new clinical cases of C. aurus in the U.S. in 2023. And it's been increasing. Like when you look at the graphs on the CDC C. aurus page, it is like, it's exponential growth right now. It is scary. Because it gains a foothold, I feel like in hospital settings so easily too, where it's just like you can't get rid of it. Right. And that's not the only species that is of increasing concern. Canada parasilosis is a whole species complex that is also found really commonly. It's not like a new infection per say, but we're seeing increases in fluconazole resistance, which is one of the main antifungals that we use, especially for like mucocutaneous infections and things like that. We also are seeing increasing rates of what is now called Nakaseomyces glabratus, which used to be Canada glabrata. That just rolled right off your tongue. I'm so impressed. I practiced so much. Like every time I wrote it, I practiced saying it out loud. But this we also are seeing both increasing and distribution. It's like the second most important species in the United States and in Northwestern Europe. But infection tends to be more severe and it rapidly requires resistance compared to Canada albicans, which tends to it's not like you can't have resistance, but it's just for whatever reason not as good at acquiring resistance genes. So there's a lot of different species that are kind of of concern and that are on the rise. When it comes to volvovaginal candidiasis, which we talked about already affects 75% of people with a vagina at least once, literally so many of us, but even recurrent volvovaginal candidiasis affects an estimated 138 million people with a vagina every year worldwide. And it's on the rise and estimated to hit close to 160 million by 2030. Okay, a couple questions. You said this is four to five times a year. At least four recurrent infections a year. Some papers call it at least three recurrent infections a year, but most most of them are four. Okay, a quick question before we talk more about about vaginal yeast infections. The other species that you mentioned of Canada, do they tend to colonize the same or like cause infections because albicans is a commensal, but these don't seem to be commensals. They seem to be pathogenic or are they? Yeah, so with Canada auris, it's so new that I don't know that we know. Okay. It like, you know, it wasn't ever found before. So has it been, you know, certainly it can colonize our skin. I think it's estimated that like 10% of people, if you just like screen people coming into a hospital or something that, 10% of people who are colonized will go on to develop an invasive infection. So it's not like it causes infection in all of them. And same thing with, you know, what is now Nacocyo-Mycosiclabritis and paracelosis. Why is that one harder? Yeah, the other ones you're like, right. And there's also, there's more too, right? Like there's other Candidol or what used to be Candida and they're now, you know, reclassified. So most of these can be found on some percentage of the human population just as commensals. But in terms of the infections that they will cause, it's the same sort of sweet of infections. In theory, in theory, yes, they could. But because I think because, especially with sea auris, we are screening for it in, we are seeing it more as an invasive infection. Okay. Where because and what does this just come down to the fact that Candida albicans is still the most prevalent. So if there's going to be an overgrowth, it's going to win out in most cases. I don't know. Okay. Certainly what used to be Candida glabrata and is now Nacocyo-Mycosiclabritis, it causes quite a lot of vaginal yeast infections. And we see, you know, paracylosis as well. So we see all of these, but still overwhelmingly, albicans is the most prevalent. So if recurrent yeast infections are on the rise, vaginal yeast infections are on the rise, are they caused by albicans or is it one of these other species? Like how much when you have a yeast infection, it's not like they will necessarily culture or do they always? Not necessarily. That's the problem. You don't necessarily have to culture to get the data on what species it is. Like where I work, we do PCRs and we can then strain type it and species type it. But you always do strain type and species type or that's what does happen? Yeah. The PCR that at least where I work, and this is not everywhere, but where I work, I swab everyone if I'm worried, try not to treat empirically. Lots of people will just get empiric treatment. And the PCR test that we do checks for multiple different strains. So it's able to different species. So it's able to tell us what that species is, which also will give us a hint as to whether it's more likely to be resistant, for example. If you're talking about an invasive infection in a hospital setting, yes, you're going to be culturing that or you're going to be doing something to figure out exactly what species we're talking about. But for a lot of muco-cutaneous infections, people might be treated just empirically, meaning just based on clinical exam, which I'll be honest, it's usually pretty obvious, but not always. And the reason I always swab is because a lot of times you've got BV and yeast overgrowth. Like it's not only just a one thing, but a lot of people will be treated empirically either because they don't have access to something like PCR or they can't afford it because it might be cost prohibitive. Or a lot like what we would do where I worked during residency is put it under a microscope and look at it under the swab, look at the swab under the microscope, and then you can see the hyphal growth, but I don't know what species that is. And so then you're at least knowing for sure that it's a yeast infection and not a yeast plus other things, but then you don't necessarily know what species it is. So it totally just depends where you are and what the healthcare infrastructure is like. And so we don't know, to answer your question of is it just see, it's probably mostly still see abacons on the rise, but it's contributed by all of these other species as well and by the increasing antifungal resistance that we see. Especially in these other species of Canada, which again are on the rises in a lot of cases. And so that is a very real and very scary aspect of Canada right now is just the rise in antifungal resistance, especially when it comes to C. auras, something like 13 to 35% of isolates are found to be resistant to essentially all the antifungals that we have. And we just detected this 16 years ago. Correct. That is very scary. I know. There's a lot of need, obviously, for research in better, more accurate and faster diagnostic tools and better treatment options. There are some that are like being fast tracked and you know, we're trying, there is actually a new drug approved for, I believe it's approved for recurrent vulvovaginal candidiasis that just got approved a couple of years ago. I guess it reduces adverse reactions compared to fluconazole, but it doesn't necessarily help with easel resistance. Another thing that's commonly used for vulvovaginal infections is boric acid, boric acid like vaginal suppositories. It's quite effective. It's like a broad spectrum antimicrobial and it generally is pretty safe and well tolerated, but it's not approved for use by the FDA. It's also not commonly used in Canada or the EU. So it's actually really hard to get access to. You have to go through a compounding pharmacy or you have to make your own suppositories. I don't really understand why. I guess nobody, no pharmaceutical company has bothered to try and make a profit off of it. Is that the answer? I don't know. Yeah, maybe it's in public domain or whatever. Why can't you just get a suppository? I don't know. I feel like I remember and I'm probably going to completely butcher this recollection because my memory is not good. But in, so last season, I did a book club episode on vagina obscura with Rachel Gross. She's amazing. In her book, she talks about using a vaginal microbiome transplant, kind of like fecal transplants for, but I don't know if it was to treat recurrent yeast infections or like a really persistent BV. But anyway, I loved that idea. I love all of the ideas that are looking more at our microbiome and our microbial communities and how they interact because we know that that's such a big driver of these kinds of overgrowth infections, opportunistic infections. So I don't know a lot about that, but it's really interesting to look into. And I feel like we were, I was a little bit like down on probiotics or like that's maybe the impression that I gave and I'm not like, I think there's a lot of potential. I just don't think we're at the stage where we can say, this will do this. No, and we're definitely not at the stage of saying put yogurt in your vagina. This is not a medical advice podcast. No. There is though also people are working on a vaccine for recurrent vaginal candidiasis specifically. It's an interesting type of vaccine because it is based on like a Canada protein of some kind. But the idea at least who they're targeting right now, like who they're testing it on is people who've had recurrent infections. So it's kind of like to reduce the risk of recurrence rather than just like something to give to the whole population or something like that. But yeah, it's really promising. I think the last paper that I saw on it, which might have been a year or two old now, they were in stage two trials. So I don't know if they've moved further from that. And then there's also a new type of antifungal that was recently approved. And the reason for invasive infections and the reason that's exciting is because it's easier to administer. You don't have to do it daily. You can do it once weekly and you can kind of front load it, which means because the other thing and I didn't even get into this because there's so many components you could talk about. When it comes to invasive candidiasis, these systemic infections, the long term sequelae of them can be really severe. And there's not enough research into the quality of life effects that we see after a systemic infection. But they're really substantial. You know, if it gets into the eye, it can cause permanent blindness. People tend to be really sick before they even get a fungal infection. And so then the recovery from that, like from a prolonged hospitalization or ICU stay is really substantial. So the fact that people are working on trying to make treatment so that it could potentially be done more in the outpatient setting is really, really huge and important. So there's a lot more that you can read about when we tell you about our sources. Sources time? Okay. Okay. Let's see. I have several, a bunch, but I'm going to shout out two in particular. So one is a book titled Fungal Disease in Britain and the United States, 1850 to 2000 by IHOMEY and Michael Warboys. And then there was, oh, if you're interested in reading like a paper about this niostatin relationship and like the hyper sensitivity candidiasis hyper sensitivity syndrome, there was a paper from 1990 published and I feel like it was the New England Journal of Medicine that studied the administration of niostatin and whether it relieved any symptoms and like anything like that. And it's called, it's by dysmukes, a randomized double blind trial of niostatin therapy. Love it. I had a number of papers for this. One of my favorites just for like overview of Canada was a nature reviews disease primers from 2024 called invasive candidiasis. I also loved a couple of papers I had about the like virulence, but my favorite I think was from the journal virulence, who knew, in 2022 titled Pathogenesis and Virulence of Canada Out the Cans. And then I have several on the introduction and emergence of some of these other species of Canada and what used to be Canada. And then the paper that was really great on recurrent vulva vaginal candidiasis was called Global Burden of Recurrent Vulva Vaginal Candidiasis a systemic review in the Lancet infectious diseases from 2018. But I've got more and you can find all of them on our website, this podcast with Kali.com under the episodes tab. You certainly can. A big thank you again to the provider of our first hand account. It really means so much to for us and other people to hear your story. We appreciate it. Yeah. Thank you. Thank you. Thank you also to Blood Mobile for providing the music for this episode and all of our episodes. And thank you to Leanna and Tom and Brent and Pete and Jessica and everyone else at Exactly Right Network for helping make this podcast and the video. Did you know we're on YouTube? Possible. And a big thank you to our listeners, our patrons. Your support means the world to us. Like we do this for you and it means so much that you actually tune in and hear what we have to say. Thank you so much. Thank you. Well, until next time, wash your hands. You filthy animals. You