[00:00:05] Speaker A: Welcome to All Cats considered, a new podcast from the American association of Feline Practitioners, where we interview professionals from across the veterinary world and take deep dives into the latest evidence based research, development, studies and guidelines that improve feline health and well being. We are the home for veterinary professionals seeking to improve the care of cats through high standards of practice, continuing education, and evidencebased medicine. In each podcast you will hear interviews from a variety of experts throughout our field, covering a wide range of topics and recent developments in the practice of feline health, sharing the key points you need to know to improve your patient's care. Let's dive in and take a listen with this week's experts.
[00:00:52] Speaker B: I'd like to welcome Vanessa bears here today, and she's going to be talking with us about invasive fungal infections and ewomycosis. So to start with, because I had to google this, could you tell us what uomycosis is?
[00:01:07] Speaker C: Yeah, that's a really great question, and I think it really highlights why sometimes people turn off when it comes to fungi, because the language is really unusual and the menclature is often changing. But basically omycetes are fungal like eukaryotic organisms, and they're kind of halfway between algae and molds. And in fact they're often referred to as water molds. And in veterinary medicine, the main species are pythium laganidium and paralyzedia. See what I mean about the Meath workshop?
[00:01:42] Speaker B: Yeah. I have to say, when I was reading through the articles to create some questions, I was like, this is the kind of stuff I will read but not remember. But I know I've got a resource to come back to.
[00:01:55] Speaker C: Exactly.
[00:01:56] Speaker B: I found it quite interesting that was mentioned in the article around potentially there's going to be some changes with the sort of geographic distribution of fungal diseases potentially due to sort of global warming changes. I just wondered if you had any thoughts about how we as a veterinary profession potentially can kind of start to track and share that sort of information.
[00:02:16] Speaker C: Yeah, this is another really great question because in fact this problem is not only relevant for human health and for cat health, but for lots of other animal species. I mean, when you think about it, millions of bats have died from fungal infections, that white bat, white nose syndrome, millions of snakes have died from snake fungal disease. So it's really, really pertinent. And in human health, some monitoring is already being done for the geographic distribution of propsidioidis and histoplasma blastomyces. In the medical field, they used data from the Medicare population of over 45 million people. And what they showed was that the geographic distribution has vastly increased. I think that when it comes to our kitty cats, there is no similar monitoring system. But actually we could do a lot. And if you think about programs or databases like the Banfield database or Vetcompass UK or, you know, that had access also to millions of medical records, it would be possible to start tracking these sorts of cases. So it's a great idea. And I think we've got the technology, we just need someone to start doing it.
[00:03:38] Speaker B: That's right. Unfortunately, in the veterinary field, a lot of these things sometimes come down to funding as well, don't they? That we've got a lot of information there, but someone needs the time and the money to be able to really explore it. I really liked that the map was in there as well, because as a primary care clinician, being able to look at something like that and go, okay, I'm working here, I don't need to so much be worried about this, but I see a lot of movement from cats and dogs coming in from these countries. But I did wonder, the areas that were blank, I'm assuming they're probably not free of these types of fungal pathogens, that we just don't necessarily have reported data.
[00:04:16] Speaker C: Another really great question. The map was a great team effort from everybody who was involved in writing the paper, so that we get all the information together and then map it. And a lot of the blanks are unknown, but not all of them. And climate comes into play as well. So if you think about the UK, it's blank. Not because of lack of research, but because actually some fungal infections are less common in the UK than in other parts of the world. And another really important thing about this map is that it only shows those fungal infections that occur in certain regions. So if you think about cryptococcus, wherever there is pigeons in the world, there is potentially cryptococcus, because cryptococcus neophormans is shed in pigeon poop. So we didn't put those sorts of infections in the map. And things like aspergillosis as well.
[00:05:15] Speaker B: Yeah, some of them are obviously a bit more common because of the risk factors.
Had another sort of question around that kind of signalman type piece, and it was mentioned that persian cats are potentially more at risk of invasive fungal infections. And do we know why?
[00:05:32] Speaker C: Yeah, that is a million dollar question, Natalie.
We do know that there are certain mutations, or single nucleotide polymorphism, also known as snps, in a particular gene called calprotectin. And that gene encodes for an antimicrobial peptide that actually has antibacterial and antifungal properties. And it does that by sequestering metals like manganese and iron. So that's known or thought, strongly thought to be implicated in dermatocytosis in Persians. Is that the whole story? We don't know. And this is really where we need the geneticists to step in and do some of their nifty research techniques, like genome wide association studying. So it's child effect. Yeah.
Find out if there's other.
[00:06:26] Speaker B: It's really interesting because I kind of knew the bit about ringworm and Persians being a bit more susceptible, but I have to say, in my head, it was like, oh, it's just because they've got so much hair.
You sort of. There's actually a more scientific reason.
[00:06:42] Speaker C: I certainly do have a lot of hair.
[00:06:46] Speaker B: Because really, for the first part of this interview, part two is going to be playing out in a couple of months.
I sort of wanted to focus especially on that sort of diagnosis side of things, and I was sort of wondering what you would advise we sort of do as a general sort of baseline workup in cases where we're potentially suspecting an invasive fungal infection.
[00:07:09] Speaker C: Yeah, look, I think there's a good case for doing basic cbc, biochem and retrovirus testing, which I always do for sick cats to just know if they're retired or felb. It doesn't mean that you can't treat them, but it's always good to be informed because you might need to treat them for a little bit longer. And even with the CBC, even though there's not specific changes, sometimes there's little, you know, hypoglobulinemia is not just all about FIP.
I know that's probably what most people probably think of when they see hyperglobulinemia in a cat, but it can be quite common in these invasive fungal infections as well. In fact, I think about 60% of cats with sporadicosis will have hypoglobular anemia. In some of the invasive aspergillosis, like sino orbital aspergillosis, it's quite common as well.
So that can be a little flag. And of course, eocynophilia. Don't just think allergy or parasites. It's not that common. But when it occurs, I always think about hungry as well. You can get hypocalcemia associated with hypoglycem and SSD associated with. You think about fungal inflammation, you get fungal granulomas and they are full of monocytes and you can get activation of the vitamin D pathway there. So that can cause hypercalcemia. And that's been seen in things like dermatophytic pseudomycitoma, histoplasmyosis, blastomycosis, things like that. So I would start there, and then I would move on to the color antigen or antibody test.
[00:08:48] Speaker B: That was actually the next thing I did want to ask you about, because it seemed for specific infections, there's quite a lot of variability in the availability, the sensitivity, the specificity.
Thinking about us, if we look in the map and we think about what diseases might be more endemic in the area we're working in, how would you recommend we sort of approach those discussions, maybe with our local laboratory to find out what testing is available and what the advantages and disadvantages of the tests that they have are?
[00:09:18] Speaker C: Yeah, absolutely.
I think the first thing is to think about what's likely to occur, as you said, in your area, and you're going to be thinking not only about where you're practicing, but also what kind of clinical signs your animal is presenting with. So anywhere in the world, if you've got a cat with nasal signs, you might want to think about ruling out cryptoplasis. And the great thing about cryptocurcosis is that you can make a dependent diagnosis on a blood test and not invasive blood tests, which is great. And then if you're practicing in the midwestern, south central or southeast us, and you've got a cat that's got respiratory distress or tachipnea or dyspnea, you might be thinking about doing a histoplasma antigen test on urine. But then if you're working in Arizona and you've got a cat with the same signs, you might think about doing serology testing for proxybinoid unwantosis. So that's kind of the first things to think about. And then the next thing, exactly as Mr. Depp did, would be to get on the phone and ask your lab to provide you with some data on what the prevalence they're getting from their data, because they're the ones that are providing the tests, and they should be able to let you know what they're seeing most commonly. But it's also good to ask them about what is the test that they're using and do they have any data on the efficacy of it. A lot of these tests have been published in terms of sensitivity and specificity, has been investigated by feline researchers. So ask the lab to provide you with those references, and that can really help you as a vet work out whether you've been used self test or not?
[00:11:07] Speaker B: Yeah. Cool. And actually that's, I guess another source of kind of monitoring data, isn't it? Looking at the lab, what's being submitted, what's coming back positive again? Is another source looking at changes and spread over time?
[00:11:19] Speaker C: Yeah, absolutely.
[00:11:21] Speaker B: And then in terms of the workup, obviously advanced imaging then came up again depending on presenting signs. And how do you decide what modality to use? Things like CT are obviously becoming potentially a lot more available than they were when I was a newly graduated vet.
Sort of a first choice or does it really depend on presenting signs?
[00:11:45] Speaker C: Yeah, I think it depends on which part of the cat you're going to image. So what is the turning presentation and also what modality you've got available to you when it comes to choice between ct and radiography?
Look, if it's a cat with nasal signs, if I've got the option of doing a CT first off, well that would be wonderful because obviously you can get really good information about the soft tissues as well as the bony structures without any problems of super imposition of soft tissues and bone that might obscure the underlying pathology. So that's great. And some practices, like for example, in quite, it's not uncommon for primary care practices to have a little ct unit in their, you know, if you're working in the country in a remote rural area, you might not have the option of that. And in that situation, then plain radio preview is a good place to start. I think also you want to think about, well, what is the best return diagnostically for you and financially for your owner. And if it's a case that you know is going to be referred, then you might think about whether it can just be done all at once. At the one time. If it's a cat that's got neurological signs and you're thinking about fungal infections, it might have upper respiratory signs as well. Well, obviously in that situation, the modality that I really want to use is an MRI. But if in doubt, take a chest x ray, because if you look at the table Sydney article, it basically goes through should I do a skull radiograph, should I do chest x rays or should I look at the skeleton? And there's quite a lot of fungal detections that do have some abnormal things like chest x rays. So it would never be a bad thing to take chest x ray.
[00:13:59] Speaker B: Actually, that leads me really nicely onto the next one that I wanted to ask around. Bronchio alveolar lavage cytology was sort of mentioned as potentially a diagnostic tool. Especially if we're sort of thinking there's respiratory signs. Is blind collection still okay in these cases, especially if you don't have access to more advanced endoscopy, especially small endoscopes?
[00:14:23] Speaker C: Yeah, absolutely.
I mean, many of these fungal infections, if they are going to cause lower respiratory disease, it will be diffused. So a blind bal is absolutely fine.
[00:14:37] Speaker B: And then with those sort of samples, is there anything additional we need to mention to the lab when we're sending the sort of fluid in for cytology?
[00:14:48] Speaker C: It's always good if you're suspecting a fungal infection, just to let them know that it's one possibility, because often for things like bal, when they're doing cytology, they're going to be using dickwick or other modified Ramanaski type stains. And sometimes the fungal elements are negatively staining. So if it's something you've flagged, your pathologist might be a little. To spend a little bit more time reading it sample.
[00:15:17] Speaker B: Now that makes sense.
There was also some really good advice in the diagnostic paper around collecting biopsy samples. Could you talk us through the reasoning behind collecting one really large biopsy and then chopping it into pieces?
[00:15:32] Speaker C: I know it does sound a bit bizarre.
Look, I'm either going to take one large representative biopsy. If I've got a lesion, I'll give you an example.
Just say a cat comes in, it's got periorbital swelling, it's got exop thalmus.
You open its mouth and you see it's got a mass in the back of the mouth. Probably this cat's got some kind of mass in the baby from the orbit, ventrally into the oral cavity. And that is like a free fit for a biopsy because it's very easy part of the anatomy to get a biopsy on. Now, much easier than trying to do an orbital sync, t guided biopsy. So you can either take three small biopsies or take one big one and cut it into three pieces. Why do we want to cut it into three pieces? Well, three different potentious tests. You want to put some obviously, into formula or histology. You're going to put another piece into a sterile tube and put it in some sterile sad and in to stop it from drying out and then pop the other bit in a clean tube and freeze it. The reason being what if a fungal infection is identified on histology? Fungal culture is negative. Then actually you can do PCR on the fresh tissue. And that actually is superior to doing PCR on formal and fixed tissue. You can actually amplify up a longer piece of dna from the fungus. And the longer the bit of dna that you can amplify, the longer sequence or read that's generated and that means you're much more likely to know exactly what species is causing the infection.
[00:17:22] Speaker B: I think that's really good advice as well. And I've heard similar advice around things like mycobacterial disease as well. And I guess the same rules apply, don't?
[00:17:31] Speaker C: Yeah, exactly the same principles, Natalie. Yeah, absolutely.
[00:17:37] Speaker B: And you mentioned fungal culture there, and reading through the article sounds like sometimes it's a little bit of a delicate thing to do.
Top tips when we're sending these samples to hopefully get the best results that we can.
[00:17:52] Speaker C: Yeah, well, transport can be your enemy.
Long delays in transport can mean that you can get bacterial contamination of the sample.
So generally, if you are so lucky as to live close to a lab and the sample can get there within 2 hours, then you don't need to worry about refrigerating it. But most people don't have that luxury. So if it's going to take longer than that, then keep it in the fridge until the courier picks it up.
And also talk to the lab, ask what do they do when they do culture? It's actually been shown that if you homogenize tissue, which sometimes is done for different tests, if you homogenize the tissue in a blender kind of thing, it might damage the funnel elements and nothing will grow. And it's actually recommended to carnal culture about baked chocolate into little tuner tuned dice bits of tissue that you're more likely to get.
[00:18:58] Speaker B: Right. Okay, so that's really.
[00:19:01] Speaker C: Yeah.
[00:19:01] Speaker B: So before you send a sample, we make a phone call as well.
[00:19:04] Speaker C: Yeah.
[00:19:07] Speaker B: And then in terms of sort of PCR, how can we sort of ensure that when we're sending a sample for PCR that we are actually detecting the causal infection and not maybe a commensal fungus or other commensal viruses or bacteria?
[00:19:23] Speaker C: Yeah, that is another really good question. And if you're sort of thinking about an invasive fungal infection, there's probably two situations in which you're going to pick the PCR bops on your lab submission form, and one of them is where you've taken a biopsy.
So for example, just say you saw a persian cat and it had skin lumps, you took a biopsy and you weren't even thinking about fungal infection. You got your histo report back and it says fungal infection mold. And you're like, oh, I didn't culture that. I wasn't even thinking about a fungal infection. So in that situation, you can actually ask the pathologist to get the paraffin block and to shave off some little sections of tissue just a few millimeters thick, and then they'll extract DNA from that. And providing the pathologist saw fungi in resection, there's about a 60% chance that you'll be able to get a read, a fungal read on PCR, and you can be really confident that that's not going to be a commensal. So when it comes to histological tissues, PCR is really unlikely to amplify it at commensal. The other situation in which you're going to be thinking about doing PCR is just say you cultured a fungus, so you might have had a cat with orbital swelling, and you might have taken that biopsy from the mouth, from the mass of the oral cavity and cultured it. And the lab reports asphagillus species, and they're not sure which one it is. They might say asphagillus humorgardis complex or something like that. And you actually want to know exactly what the species is, because the species can influence your treatment. The best way to get an identification in that situation is to ask the lab to do PCR on the fungal culture material itself. So they're going to take a little piece of the colony, they're going to extract DNA, and you're going to do PCR for some fungal genes, and that will give you the diagnosis, and obviously.
[00:21:35] Speaker B: Yeah, that's a nice clean sample of such, isn't it?
[00:21:38] Speaker C: Yeah, exactly.
[00:21:41] Speaker B: And then I did just want to touch a little bit more on cryptococcus, because it did seem to be one that might be a little bit more on the rise, especially under global warming. What sort of tips would you have for us, where this really would be quite a new disease for us to be adding to our differentials list, what are maybe the key things we need to be aware of?
[00:22:01] Speaker C: Yeah, sure. So there has been quite a bit of research done looking at climactic modeling, and we know that cryptocurcosis can be caused by the two different species complexes, the neoformins and the gaddai and the neopormans. Wherever there's pigeons, we get cryptocurrency Formans. But cryptocus gaddai is really increasing in its geographic range, according to these models. So, yep, we should be on the lookout. We might be seeing it more frequently in places like Europe that are becoming more suitable for its survival. And if you haven't seen cryptococcus before, it can be a little bit deceptive. So when I first came to Hong Kong, there was a general perception that there wasn't really cryptococcus here. And in fact, a colleague saw a cat with a proliferative mass on its nose, a huge mass, and it had been referred as a suspected tumor, and it ended up being cryptocurcosis.
It can look like a neoplasm. So in terms of the most common disease forms, it's nasal CNS and disseminated. And nasal crypto can present in multiple different ways. So you can have mucopyl nasal discharge, serosanguinous discharge. You can have a polypoid mass protruding from the nasal cavity. You can have the draining sinus. You can have facial distortion. You can also get exophtalmus occasionally with cryptocurrosis associated with development of fungal granuloma in the orbit. You can have a nasal plan of mass. And if there's a fungal granuloma in the back of the nasal cavity, in the nasopharynx, then that cat might present with sturgis or snoring breathing. Lower respiratory disease is less common, but it can occur, and then most commonly, a cat's going to present for kidneya or dyspnea. The upper thing is that crypto likes to track from the nasal cavity through the crib reform plate, track along the optic nerve, and you can get a cat that presents with sudden blindness due to bilateral modiasis. That kind of case. If I've got a younger cat suddenly blind, I might also ask the owner, well, has it had any sneezing or nasal signs in the past few months? That can be a clue as well. And then when it comes to the disseminated form, you can get nodules or ulcers anywhere or all over the body. You can even get little nodules in the tongue or on the gum and some of the meatles.
[00:24:49] Speaker B: Gosh. So it really can look like almost any kind of paddle.
Yeah. Really useful to have that really broad sort of thoughts about the kind of thing to be adding it on. And I guess it kind of comes back to the point that you raised about these often being fungible granulomas. And I guess the presentation can be like other types of granulomatous disease, but really useful to know. Think about it starts from the nose almost, doesn't it?
[00:25:18] Speaker C: Yeah, absolutely. And with crypto, that's exactly where it starts. So when the cat inhales those little basidio spores, they get deposited in the nasal cavity, and they go from there.
[00:25:31] Speaker B: Yeah, definitely. The article contained a lot of really useful additional material around specific infections as well. And I have to say, as I was reading through it, I was saying earlier, I'm not going to remember 90% of this, but I've got a very nice resource to come back to. Examples, just as a sort of finishing up this sort of question around the diagnosis, what would be your top tips for our listeners to be thinking of? If we need to be thinking fungal, when should they consider moving these sort of infections? Maybe upset differentials list?
[00:26:07] Speaker C: Yeah. Thank you. I'm a big fan of using patient signalant and pattern recognition to help me rank my differential diagnoses. And I guess in the same way that it's a no brainer to think about FIP when you're presented with a six month old purebred cat with a fever and abdominal distension, I'm going to rule out cryptocursis first in any cat with nasal signs, it's part of my minimum database to just pop a latex cryptocopyal antigen teeter test into my workup. And then, similarly, if I'm presented with a persian cat with skin nodules, that's almost. Well, I've got to rule out the matter fitting pseudomycitoma. And if you're not familiar with that, that's when superficial dermatophytosis invades subcutaneously and forms a mass. And then thinking again about breed, if it's a Persian or a related cat, like a himalayan and it's got nasal signs, I might be thinking that aspergillosis is moving higher up on my differential diagnosis list. And then if I see any cat with exopalmis and I can't retropulse the globe into the orbit, I know it's really highly likely to have an orbital mass. And when I'm thinking about orbital masses, I'm thinking about fungal neoplasia. Very aplasia can be a bacterial abscess, but again, would be another situation where fungi is going bio on the list of differential diagnosis.
[00:27:37] Speaker B: Brilliant. Thank you for that. I think that's been really helpful to start to think about these kind of infections, how they might be increasing in prevalence, especially in some places in some countries, and what we need to be thinking about to diagnose them. So part two of our podcast with you is then going to be very much focusing on the treatment. So that will be coming for people in the next few months. But thank you very much for talking about the diagnosis with us today. Vanessa.
[00:28:06] Speaker C: Oh, that's my absolute pleasure. Thank you doubley thank you for listening.
[00:28:10] Speaker A: To this episode of All Cats considered. We hope you enjoyed this interview. For more information on the topics discussed during the episode, please be sure to head over to Catvets.com and explore the links in the podcast description. And please be sure to subscribe to this podcast and your platform of choice so that you don't miss any episodes as we release them, have thoughts or ideas about the interview you heard today? Share them with us. Leave us a comment on our facebook page, or shoot us an email at
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