103. Fungal infections overview and series intro

My my! Mycology?

Join Callum and special co-host Alyssa for this, the first in the all new ID:IOTS Mycology Mega-series.

Here we cover:

1. What the British Society of Medical Mycology is and what they do 
2. Why we're doing this series on fungi  
3. The Global and UK Burden of fungal disease. 
4. The spectrum of fungal disease clinically, 
5. The taxonomy of these pathogens, 
6. and the WHO Fungal Pathogen List.

Notes for this episode can be found here.

Transcript

Callum: 0:00

Hello, Alyssa.

Alyssa: 0:01

Callum.

Callum: 0:02

It's my pleasure to introduce this first episode in our upcoming fungal series. And to introduce Alyssa, who is our. Co host for this series. I'm Calum. I'm gonna be your fun guy for this series. And I'll pass over to Alyssa to introduce

Alyssa: 0:21

So I'm Alyssa. I'm gonna be with Fungal for this series. I am a microbiology registrar, dine and Exeter, and I've got an interest in fungal infection. so I did a clinical research fellow post at the, Exter Center for Medical Mycology, researching fungal diagnostics for mu Mycosis. And I'm the, British Society for Medical Mycology, or BSMM, Junior Clinical Representative. and I'm really happy to join Callum on IDX podcast. to talk more about congenital infection.

Callum: 0:56

Great. Thanks very much for coming on this and for suggesting this collaboration in the first place, which both Jane and I are very excited about the British society for medical mycology. Now I'll be completely honest. I wasn't aware of the society before you got in touch and we'll talk about how fungal stuff is maybe not on everybody's radar as much as it should be. So could you tell us a little bit about what the BSMM, who they are, what they do?

Alyssa: 1:28

Yes, the BSMM is a really longstanding, society in the UK actually, 60 years. and it really aims to bring together clinicians and academic researchers who are interested in fungal infection. So the society supports, numerous conferences. So we're going to be doing a fungal session at Fizz this year. It publishes national guidelines and recommendations, and holds a three day annual conference every year, which is a real mix of clinical and academic research and presentations. so the upcoming BSNM 2025, is the 59th meeting, and it's going to be in September So membership is only 30 a year, and these benefits include, reduced conference fees. But also access to travel grants if you're presenting anything at a conference, which is fungal related. and there are other funding options as well. we've got a website, which is the smm. org, which has got more information about the society.

Callum: 2:34

Great. Yeah, I've had a look at the website and it was really interesting to hear more about the society and what you've been doing and yeah, I'm certainly going to, or will have been at FIS this year. So I'll be sure to check out the fungal session and pick up some tidbits there because Well, I guess that comes under my next question, which is why? Why are we doing this series? Like, why do we why do we even want to talk about fungal disease?

Alyssa: 3:00

So I don't know about you, but I've found that throughout my infection training, fungal infection feels really underrepresented. So, there's a lot of focus on bacterial infection, viral infection, but we really don't get taught a huge amount about fungal disease. And yet, lots of our patients are at risk of fungal infection, and it causes huge amount of morbidity and mortality, which we'll come on to in a minute. so, with this series of podcasts, we're really aiming to Cover a wide range of topics and to introduce listeners to the field of medical mycology. Highlight some additional resources and really dive deeper into the fungal world.

Callum: 3:46

Yeah there's a lot planned and Alyssa has been Working hard to coordinate and there's some really exciting guests who are going to be coming on some very prestigious ones, and one idiot but the, yeah, the sort of things I think we're going to be covering is this episode, which is a bit of an overview, looking into diagnostics, going through the yeasts The molds, the dimorphics, looking at antifungals, and then finally some stuff about the sort of laboratory antifungal testing, and some other extra bonus episodes, hopefully. And so, yeah, I think this is Really important, as you say, and I completely share that. I am nearing the end of training and I still find when there is a complex or unusual fungal infection, or even quite straightforward fungal stuff is something that maybe feel a bit less comfortable with

Alyssa: 4:47

yeah.

Callum: 4:48

because it is more unusual, isn't it? Or is

Alyssa: 4:51

Or is it? Exactly.

Callum: 4:53

Or is it?

Alyssa: 4:54

Are we just not? Are we just not thinking about it enough? We just not diagnosing it enough. So shall we move on and talk about the global burden of

Callum: 5:05

think that'd be Great, because this is a UK based podcast but thinking about the global health impact is obviously important in infectious diseases and there's a lot of this which is important for the UK but also for the rest of the world and we've got lots of international listeners so to hello to everybody in all parts of the world.

Alyssa: 5:27

so fungal infection really does represent, an important and also growing cause of disease and of death worldwide. so there was a recent paper in Lancet ID by, Prof. Dedding, this year, which estimated that over 6 million cases of severe fungal infection occur each year. With a 2.5 million deaths. and I think another paper that, that sort of helps put this in perspective was, by Gordon Brown back in 2012 when they estimated the annual death 12 to be 1.5 million. So in the last 10, 12 years, it's really increased hugely. and this rise in mortality is probably due to the fact that. fungal pathogens that generally all around us or their colonizers, and they're opportunistic. And we've got an increasing number of patients at risk of serious fungal disease. And that's because our population is becoming more immunocompromised due to advances in medical therapies, like solid organ transplant, stem cell transplant, use of chemotherapies and biologics. So that's probably why we're seeing this. this rise in serious, fungal infection.

Callum: 6:46

That's huge. And we noticed that, if you're working in infection, we're probably being consulted on someone who has a biologic that you've never heard of before. And that's increasingly common. And as we're getting more precise with our immune suppression, it potentially that and more broad immune suppression we're seeing unusual consequences of these sort of immune cascade. And as you say that they're all around us, I was always shocked in the lab where I think we just, when I was first training and they got us to leave agar plates out on the bench to see what was growing. And you're like, there's so many fungi. I think someone was saying that because fungi, and you can correct me if I'm wrong, because they're a bit more resistant to things like desiccation and UV and so on they stick around in the environment so much better. So if you're out and about you're breathing in the air there's so much they're all around

Alyssa: 7:38

there are fungal spores, yeah, everywhere in the air that we breathe. And we breathe in thousands every day, but our immune system just clears them. Whereas if you're immunocompromised for whatever reason, you don't have neutrophils, you don't have T cells, then these fungi can start growing and cause disease. and I think some other stats that really help put the burden of mortality of fungal disease in perspective is comparing it to, other important, diseases, say HIV, malaria, and TB, and the WHO in 2022 reported that 1. 3 million people acquired HIV. in 2022. and there were 630, 000 deaths from HIV. malaria, there were lots of cases malaria. So 249 million cases globally with, 600, 000 deaths and TB 10. 6 million cases globally with 1. 3 million deaths. I think what this highlights is that whilst collectively there are far more cases of HIV, malaria and TB. annually, there are pretty much the same number of annual deaths caused by fungal disease. There's all three of these put together. and I think that's something that's really important. You might not commonly see these infections, but when we do, they are frequently fatal.

Callum: 9:13

Why do you think that is?

Alyssa: 9:15

I think part of the issue is a lack of diagnostics. Save enough. We're not necessarily diagnosing invasive disease, serious fungal infection, early enough. and also a lack of, antifungals. When you think about how many classes of antibiotics we have, we've only got four classes of antifungals. and, somebody can't use one of those because of, liver disease or renal impairment that further narrows down, your options for treating them. And also, if you look globally, there are lots of antifungals that just aren't available in certain parts of the world. like ZO1 for teratin B,

Callum: 9:55

and that's a really old drug. It's Jayme and I were talking about this recently on where are all the new drugs going. And there's obviously the WHO essential medicines list, which there are antifungals on and we're very privileged in the UK to have access to a lot of drugs. Maybe not all of them, but most of them at least.

Alyssa: 10:13

yeah. And it'll be really interesting, some of the guest speakers that we're going to have on in the future episodes have worked abroad and, and experienced this lack of access. It'll be really interesting to hear from them because we are so privileged in the UK.

Callum: 10:28

So you said serious fungal disease. So that's quite a scary stat. And certainly recently I guess there's been quite a lot of media attention to things. So the one that springs to mind is mucormycosis and India in relation to COVID and steroids and high glucose. And You talk about media representations like The Last of Us, which was a great series maybe not super realistic to what fungal disease is doing, but highlighting it to the public. But what about the non serious disease? Where is that sitting?

Alyssa: 11:02

so fungi cause a huge burden of non-life threatening disease as well. So thinking about your superficial mycosis, so infection of the skin, hair, nails, mucus membranes, and whilst these aren't gonna kill you, they can be hugely bothersome for people who have these infections. and just as an example, so about 70% of women. will experience, vulvobaginal candidiasis at some stage during their lifetime. And millions of people suffer from fungal toenail infections. So it's important not to forget these more superficial infections that aren't going to kill us, but cause a huge amount of bother to patients.

Callum: 11:46

Yeah, that morbidity is massive. And again, as you said, there's limited treatment options for the severe disease, but for the sort of superficial disease we're talking about months of therapy potentially with significant side effects, and then you reach an intolerance and what do you do with it? And also we thinking about other things, although these might not be that severe in their, in themselves, they might open you up for risk factors for other things. So we quite often talk about things like tinnitus and the risk for cellulitis or more invasive disease. So contributory to other associated health problems. So we've touched on superficial and we've talked on some sort of more severe things What would you how would you divide up the spectrum of fungal disease in the sort of a clinical division? We'll come on to the sort of taxonomy, which is I think it's quite confusing So we'll try and boil that down to make it understandable. But if we're talking about fungal disease clinically How would you divide that up?

Alyssa: 12:49

So I, I think of fungal infection in four main groups. So superficial or mucocutaneous, so infection involving skin, hair, nails, mucous membranes. So that's things like, like you said, tinea pedis, which is fungal infection of the foot. Onychomycosis, which is a fungal infection of the nail. Oral, vulvo, vaginal candidiasis. then you've got slightly deeper, so subcutaneous infections. so Mycetoma, also called nodura foot, or sporotrichosis. Then your invasive fungal infections, so these are your serious, more life threatening fungal infections that cause fungemia, pulmonary disease, or disseminated, infection. So that's things like your invasive candidiasis, invasive aspergillosis, mucomycosis, and pneumocystis pneumonia. And then fourth category, probably allergic. so fungi can cause allergic reactions in lots of people, particularly if you've got predisposing condition like asthma. so an example of that would be allergic bronchopulmonary aspergillosis.

Callum: 14:08

Yeah, anybody who's worked in a respiratory center will be used to trying to diagnose that and sometimes, as you say, the diagnostics you mentioned earlier on were limited and it can sometimes be tricky to decide which category your patient fits into that patient with a chronic lung disease, there's aspergillus and the sputum recurrently, there's imaging changes is that invasive? Is it colonization? Is it allergic? What's causing the patient's symptoms?

Alyssa: 14:36

exactly.

Callum: 14:37

So yeah I think that's a really useful way of dividing them up and we'll, aim to, to cover those, I guess in this series, we're probably going to focusing more on We're going to talk about superficial

Alyssa: 14:53

So we're going to talk about the yeasts and then the mould. and within that, yeah, we'll talk about, how some of them can cause superficial infection, as well as invasive infection. And then one of our mold episodes is going to look at dematophytes, and mycotoma causing mold. That will focus more on, superficial infection, your subcutaneous infection caused by those agents. So I think it will be a bit of a, yeah, a mix.

Callum: 15:21

That's great. I have to say now I don't know if other people will relate to this or not, but as an infection specialist, you're often consulted Or there might be a guideline which says say you're a general practitioner and you're dealing with superficial fungal infection. And it'll say like, try these treatments, and then it'll say at the bottom, consult infection specialist, right? And then they call you, and you're a junior registrar, and you've never really dealt with that, and you have a lot less clinical experience than the general practitioner. And then you look up the guidelines yourself, and you're like, oh that's me. And yeah, so I'm looking forward to that as well because I find those cases quite tricky because I don't really see it much myself and I'm getting contacted on what's a third line, fourth line treatments here and it's not straightforward. So I guess we're saying severe, non severe, but for the patients that can be so, and it it's so difficult to manage

Alyssa: 16:17

yeah. And I think also, like you said, we only get consulted about cases of vaginal candidiasis when the patient's gone through multiple treatment options and, you really got to think outside the box at that stage. So definitely we'll go through some useful guidelines, And hints and tips for treating things like that

Callum: 16:39

Great. So that was the clinical spectra, and now let's, so the taxonomy, so this is tricky taxonomy is always changing as we get more data and taxonomists working hard to make sure that things are precisely in the right box. But sometimes that makes it quite confusing and maybe come on to more in yeast. So how do, how would you divide these up? In the taxonomy? Okay.

Alyssa: 17:05

so basically there are three different fungal kingdoms. So you've got your basidiomycota, your ascomycota, and your mucomycota. So mucomycota used to be called zygomycota, which is one of the big changes that's happened. We used to call mucomycosis zygomycosis, and that's why. And most of your human fungal pathogens are in the ascomycota kingdom. So basidiomycota, um, It's just got yeasts in it. Malassezia ferfea

Callum: 17:42

Trichosporin,

Alyssa: 17:43

and rhodotorola. And then your Ascomycota kingdom has got a mixture of yeasts and moulds and your dematophytes. And

Callum: 17:54

Yeasts first up we've got Candida,

Alyssa: 17:58

Fusarium.

Callum: 18:00

and then in Molds we've got Aspergillus, and Alternaria. Microsporum, and

Alyssa: 18:07

Yep, and then you've got your dematophyte moulds, so your trichophytin and

Callum: 18:11

you've got

Alyssa: 18:13

epidermophytin. Exsophiala. And

Callum: 18:19

moulds, we've got Phon Oh yeah,

Alyssa: 18:23

Pseudalacheria. I

Callum: 18:34

Phoncescaea species. Is that right?

Alyssa: 18:36

think so, yeah.

Callum: 18:38

Blastomyces,

Alyssa: 18:40

you've got your dimorphic fungi. So that's histoplasma, coccidioides,

Callum: 18:49

Paracoccidioides,

Alyssa: 18:50

talaromyces.

Callum: 18:51

and Sporophyx,

Alyssa: 18:54

And then finally you've got your, mucomycota, kingdom. so that includes your, uh, mole. So that's just moles in that kingdom. So it includes your mucorales order. Yeah.

Callum: 19:07

Rhizophos,

Alyssa: 19:09

Nucor,

Callum: 19:11

Lichthymia, which used to be called absidia,

Alyssa: 19:15

Anconigamela,

Callum: 19:17

In the entomophorales order, we've got canidiobolus.

Alyssa: 19:22

and Vesidioglis. So

Callum: 19:26

all the fungal pathogens, yeah?

Alyssa: 19:27

the fungal pathogens. So that's just some examples of the main ones in those

Callum: 19:36

um, if too many to try and remember. I guess it's like a lot of things where you see these on a piece of paper or a notes page and you think It's overwhelming. But certainly for me, there's a couple of bits in there that stand out because I've dealt with that clinically. So then you start to be able to categorize it. So hopefully that helps you Think what, just a question for me and you, we can cut this out if we don't have the answer. But in terms of the free fungal kingdoms, what sort of differentiates that? Is that just a sort of purely genetic taxonomic differentiation or in generally do you see patterns between the sort of Presidio um, ASCO and Mucor? My Cota in terms of what they're like

Alyssa: 20:19

Yeah, so you get distinct fungal species within them, but it's a taxonomic thing really about at what stage in time they, how they diverge, and that's kind of how they're grouped, but they're not clinically similar, I wouldn't say.

Callum: 20:40

cause I've always found it tricky, we've got the and then you talk about micro, my Cota. And then you talk about Mucor, which is a specific genus within the order of Mucorales within the kingdom of Mucormycota. And because the names are quite similar, you're like, when you say Mucor what are you talking about? But that makes sense. And we've talked about Yeasts versus moulds versus dimorphic fungi. So could you just explain, what those terms mean? Because again, I think that's something that people will be like, generally we'll use yeasts, moulds, fungi fairly interchangeably in lay communication, I

Alyssa: 21:17

Yeah, absolutely. And I think that's an easier way of thinking about it than The different kingdoms more for like information, it's not as clinically useful. So yeasts are single cell organisms that generally reproduce by budding. So one yeast cell will bud, bud off another yeast cell. and when they're cultured on the plate, they're waxy colonies. Where's molt? and multicellular organisms, and they reproduce by producing spores, which we've already talked about. These are cells that are quite resistant to environmental stresses and allow the fungus to survive really well in the environment. and from these spores, they produce hyphae, and you get lots and lots of hyphae, and it gives it that furry appearance when it's cultured. so waxy single cells are your yeasts, and your furry multi celled organisms are your moulds. And then dimorphic fungi, can interchange between these different phases. So, they're moulds in the cold, and they're yeasts in the beast. That means that

Callum: 22:30

That's great.

Alyssa: 22:31

And we're the beast.

Callum: 22:32

Yeah.

Alyssa: 22:33

so they're, at sort of environmental temperatures, they grow as fluffy moulds. And then when the pathogens in a human, they switch to a yeast phase, when they grow at 40 temperature, and you can actually get them to switch in the lab by growing them at different temperatures. And that's part of the way that you identify that it's a dimorphic fungus.

Callum: 22:58

That's a really understandable explanation of it. It took me a long time to get my head around this, particularly for exams. I always found that fungi were bits that, you know, and also the sort of diagnostics, microscopy, appearances how they grow is complicated. I recently I was thinking Maybe this isn't relevant, but looking at the food in your fridge I had recently had some kimchi, and it was covered in these sort of like white, waxy spots. Oh, that's a yeast. Great. Very appealing. It should be there it's a fermented food, so. There's yeast in it. And then moulds is like you've forgotten about your yogurt and you open it and it's that green, fluffy you know, aspergillus, uh, sitting there, which is again, not particularly appealing or your bread you look at your bread that you've not looked at. I'm making it sound like my food keeps going off. It's, and then dimorphic fungi shouldn't really be seeing in your food, in the fridge. That's quite a limited geographical, distribution, thankfully.

Alyssa: 23:59

I did an assembly for a group of primary school kids in London about fungal infection and, the immune system. And what I did to try and help them understand it is I got two strawberries, and I poked a hole in one of them, and the other one I just left as it was, and then I just put them in my midday. So. And I took a photo of them every day. and it was thinking about, even a strawberry has an immune system, so it's got that barrier, like we have our skin as a barrier to the outside world. and got them to think about what would happen to the strawberries. and obviously the one that had the break in its barrier, went all mouldy. really quickly. And the other one was, still fine. I think I ate it on about day six. And that, I think that's just a really nice way of sort of, you know, fungi are around us, and spores just land on stuff. And if it's not protected because it's got, a defect in its immune system, whether that's cellular, femoral, or barrier immunity. then you become susceptible to infection. My love for

Callum: 25:22

having a nice example. In the prep notes um, this is really, um, put this table together and some of the things there, so candida, pneumocystis, and aspergillus are in red. So why, why have you got those in red?

Alyssa: 25:35

So those are the main fungal, pathogens that cause serious UK. So they're the main fungal killers that we'll see in the UK. so those are probably some of the most important ones to see. And one thing when I think about, like, how serious is the burden of fungal infection in the UK is that we just really don't know, there's no, mandatory reporting or surveillance, of these fungal diseases and also diagnostics pretty imperfect. So it's hard to know exactly. how many people are getting these serious invasive infections and how many people are dying for them. and there are, several papers that sort of estimate this burden. and generally they also highlight this level of uncertainty. but a point that I want to come back to is that we know that our population who's at risk of these serious infections is growing. Because we've got an ever rising number of immunocompromised patients who are susceptible to fungal disease. So whilst we don't know exactly what the burden is in the UK, I think it's going to become increasingly important.

Callum: 26:49

I think that's all the more reason to get your head around it, isn't it? so I guess that's the UK perspective globally you've got the World Health Organization now understand that they publish a fungal priority pathogen list. Good.

Alyssa: 27:03

Yeah, so that, that was published in 2022. And that is a really important document. and it's really the first document that has put fungal disease on the global priorities list. so it really recognizes the emerging global health threat of invasive fungal disease. and it recognizes that we've only got four classes of antifungal drug and there's rapid emergence of resistance developing to these drugs. and there's also a lack of diagnostics and. we don't have vaccines, so we don't have any preventative measures in place. so this fungal priority pathogens list, really aims to highlight these issues. and strengthen laboratory capacity to diagnose these infections, highlights the need for surveillance of fungal infection and seeks to really drive investment and research. very much. into a fungal infection, which is an unmet research and public health, need.

Callum: 28:20

Yes, hugely important. I didn't know about that.

Alyssa: 28:23

Yeah, no, it's big news in the myc, mycology world. It's like, yes, someone's finally recognised! These infections are important.

Callum: 28:34

And as you say might be the, something to start the ball rolling on more work on this. Is there any having at that, is there anything on there that you're surprised about? Or anything that's not on there that you maybe think should have been? Or does it hold up what people were expecting?

Alyssa: 28:51

Yeah, so I think that's been a fair amount of, discussion about, that sort of graded the pathogens as critical, high priority, and I think it was medium priority. So there's been a lot of discussion about, why one pathogen got critical, whereas another one only got high.

Callum: 29:10

Hmm.

Alyssa: 29:11

And, I think there's been a bit of controversy about how different pathogens were graded in things, but I think From my perspective, it's just important that list is now there and there's something in writing that says this is a serious global health threat and we need to start doing something about it in a more sort of, structured way. so I think that's the main take home message from it.

Callum: 29:40

I've embedded that document in our show notes, which you can find if you go to the link in your podcast player of choice at the bottom of the episode so just to wrap up, this first episode so we've talked a little bit about what the British Society of Medical Mycology is and what they do, why we're doing this series, yes. Global Burden along with the UK Burden. And then the spectrum of fungal disease clinically, the taxonomy of these pathogens, and the WHO Fungal Pathogen List. Now, I don't know how I would wrap this up.

Alyssa: 30:15

I don't think we've got much room for any more in this session.

Callum: 30:19

Ha ha ha Great.