#15 – Mold in the Body: What Is Aspergillosis?

00:00:06: So, spores are produced by aspergillus and they can fly in the air.

00:00:11: They're also called conidia.

00:00:13: You can for example inhale this conidio or these spores And when you inhale those spores then at risk

00:00:33: Virological

00:00:35: with Florian Kramer

00:00:46: Hello and welcome to today's episode of ViroLogical.

00:00:50: This was recorded in Vienna and Linz Both cities in Austria on May sixth of twenty-twenty six and today we're going to do something a little bit different.

00:01:03: We are actually not gonna talk about viruses, but we'll be talking about fungal disease.

00:01:08: so I'm doing an excursion here!

00:01:11: And i am NOT an expert in fungal diseases...I have no clue about funguses.

00:01:16: the only relation with them is that they like to go hike in the woods collect mushrooms eat them but I don't know anything about fungal infections.

00:01:29: And so today, I invited Helmut Salzer a colleague of mine who is professor at the Johannes Kepler University in Linz and also head of the Division of Infectious Disease and Tropical Medicine at the Kepler university hospital.

00:01:45: He's an absolute expert when it comes to fungal infection specifically for aspergillosis.

00:01:52: So welcome Helmut and thanks for making the time today to talk with me.

00:01:57: Thank you Florian, thank you for your invitation!

00:01:59: So Helmut what are these fungal infections?

00:02:01: And what is aspergillus and what are aspergilosis.

00:02:05: What do we know about this pathogenz?

00:02:08: Well Aspergilos is a genus of molds so in other words it's not one single organism but group related fungal species.

00:02:22: So the most important species in human lung diseases is aspergillus fumigatus, for example.

00:02:29: And this aspergilus—this mold can cause different diseases and it depends very much on the immune system of the host or of humans.

00:02:43: so you think about three different patterns first invasive form where the fungus grows into tissue.

00:02:55: Second, the chronic form which develops over months in a damaged lung but those people usually have an immune system that works well so they are not immunocompromised.

00:03:12: and third there is an allergic form Which actually isn't an infection But it's also interesting because Yeah, the same pathogen.

00:03:22: It's again aspegillos and this is ABPA a complicated word.

00:03:27: it's allergic bronchopulmonary aspergillosis And this is more an immune reaction rather than a deep tissue Infection.

00:03:38: we're going to go into different types of diseases in more detail I guess.

00:03:43: but so how common Is this pathogen, right?

00:03:47: How do you get infected.

00:03:49: Um how prevalent is the disease?

00:03:52: um You know Do you get affected by interactions with animals with other people?

00:03:57: How does it start?

00:04:00: Yeah This is completely different for example to other pathogens because we are talking about fungi and as you may suggest that this found in soil In compost and dust.

00:04:12: You can have quite a lot of aspergillus during construction works in the environment or also indoor rooms, so indoor air.

00:04:22: When you have a moldy surface indoors then it's quite high a load of spores, so spores are produced by aspergillus and they can fly in the air.

00:04:35: And there also called conidia.

00:04:38: you can for example inhale this conidio or the spores.

00:04:42: when we inhale these spores then your at risk depending on your immune system if you may develop disease.

00:04:50: but to be very clearly Every one of us probably inhales spores on a daily base, but not every one gets infected or develops the disease.

00:05:03: So it's very common to mold the aspergillus into an environment and it is very common that we inhale the spores, the conidia... ...but of course not everyone gets a disease or infection data and the epidemiology, so on a frequency of these infections.

00:05:26: It's very hard to get this data because diseases are difficult to diagnose.

00:05:33: So one important aspect why it is so difficult to get robust numbers.

00:05:40: But for example two years ago David Denning who was one of most prominent researchers in this field did a very nice work published in the Lancet Infectious Diseases.

00:05:51: And he estimated that more than two point one million people develop invasive aspergillosis each year worldwide, nearly the same number for chronic pulmonary aspergilosis so around one point eight million each year.

00:06:09: and for ABPA it's even more... It is more then four hundred million affected adults worldwide.

00:06:17: so this is quite a huge number.

00:06:20: and when we look to the estimates concerning the mortality then, this also very impressive because the estimate are around three point eight million deaths worldwide.

00:06:37: caused by invasive fungal infections, which is not only aspergillus also other fungal infection but a huge part of that is aspergilous related.

00:06:47: So this for sure the most relevant fungal pathogen.

00:06:53: concerning prevalence and mortality numbers

00:06:58: Those are really high numbers.

00:06:59: I mean, i always like to bring the comparison here with influenza where we have between three hundred thousand and six hundred fifty thousand deaths every year.

00:07:07: but it seems that this fungal diseases these forms of aspergillosis actually unfortunately kill more people than even influenza right?

00:07:16: But what you're basically saying is... We can't escape!

00:07:19: The spores everywhere.

00:07:20: everybody basically inhales them But if you have a healthy immune system and an undamaged lung, it doesn't seem to be a problem.

00:07:29: So what are the risk factors for different diseases?

00:07:33: How do these diseases exactly look like?

00:07:36: And what can we do about

00:07:38: them?".

00:07:39: Yes so always remember that the immune system plays key role in this infection or to handle this pathogen, the aspergillus.

00:07:50: see a patient with heavy immunosuppression.

00:07:55: So someone who is really immunocompromised due to solid tumor disease and receiving chemotherapy, for example then the immune suppression is quite heavy And those patients have risk of developing an invasive palmonary aspergillosis.

00:08:18: you inhale the spores and the spore are not only on their surface, they're now able to invade the tissue.

00:08:28: So this is why we call them invasive palmonary aspergillosis so that they get invasive into the lung tissues in the vessels And these can cause a quite acute very severe and also life-threatening infection.

00:08:45: So this is something which has an acute infection, found in heavily immunosuppressed patients.

00:08:53: This is the invasive pulmonary aspergillosis.

00:08:57: and comparison when you have a immune system that's not suppressed for example patient with lung damage Then you have also a risk to develop an infection with aspergillus, but this is not invasive aspergilosis.

00:09:18: So it's chronic palminiaspergiloses.

00:09:21: so the difference that the risk factor is different one.

00:09:25: The risk factors are not weak immune system and the risk factors is lung damage.

00:09:31: if you have severely damaged lungs then To clear the aspergillus or to clear the spores that you are inhaling, and then this can cause chronic inflammation.

00:09:46: And this chronic inflammation leads to the fact that aspergilos cannot grow into the tissue.

00:09:53: so it's not becoming an invasive disease.

00:09:56: but this chronic information itself damages again the lung tissue lung capacity that you'll probably develop hemoptysis, so blood in your sputum.

00:10:12: So also a very severe disease.

00:10:14: but the fact of time is completely different!

00:10:18: In invasive diseases we are talking about days or weeks and chronic pulmonary ospecialosis we're talking months even years... The factor-time is completely.

00:10:35: those two risk factors are crucial for both of the infections.

00:10:43: And I guess the allergic disease, right?

00:10:46: That's more acute, i assume.

00:10:49: Yes you're right.

00:10:50: The allergic bronchial pulmonary aspergillosis or short ABPA is an allergic disease.

00:10:59: so your allergic to aspergyllus and this often you can develop an exacerbation, for example.

00:11:11: And then it's in acute disease as you said correctly.

00:11:14: so you have difficulties with breathing and quite a lot of sputums or mucous production.

00:11:21: This mucus is very solid It has hard mucus or dense mucus which is classic for ABBA.

00:11:32: And if you have an exacerbation of this allergic reaction to aspergillus, then you need something... ...to step down the immune system.

00:11:44: So you need corticosteroids for example.

00:11:46: so a completely different disease and a completely... ...different theropoietic approach but also in very interesting and severe diseases here.

00:11:58: When we think about mortality rates with these different types of aspergillus infections, how does that look?

00:12:05: I can imagine the invasive aspergilosis.

00:12:11: I mean, that sounds like it's probably really life-threatening and could damage the lung so severely.

00:12:18: people die very quickly.

00:12:20: It actually did remind me of... You're probably familiar with the white nose syndrome in bats In North America where fungus grows through the nose tissue of bats during hibernation.

00:12:34: Remains me of that and that's deadly in the beds too, right?

00:12:37: So but how does the mortality rate look like for these different diseases?

00:12:42: Yeah so the mortality is high For both of the diseases But the factor time as I said it's different.

00:12:49: But if we look closer to the invasive aspergillosis Then we have a mortality rate of forty percent Sometimes even higher patient cohort.

00:13:05: So how heavily immunosuppressed are they?

00:13:09: It depends on comorbidities, so do they have other health problems?

00:13:18: and the third factor which is very important of course quite challenging sometimes, so there is not a single perfect biomarker to diagnose the disease.

00:13:40: So you always need different factors—you need different characteristics which have to fulfill —so you need that patient having their risk factors or at least any evidence of the aspergillus.

00:13:58: This could be for example the galactomonand test.

00:14:02: This is probably one of the key diagnostic assets, what we have to diagnose invasive pulmonary spitalosis.

00:14:09: So this is a component and the galactomanan.

00:14:15: And by detecting that galactomanan there are different cutoffs.

00:14:18: for example, you can do this from their lung secretion but it also comes with blood.

00:14:26: But as I said its not perfect.

00:14:28: so You need a positive biomarker or patient at risk and other factors which i don't want to explain now in detail to create a little bit of awareness that the diagnosis is not so easy and also, disease presents very unspecific.

00:14:49: So you probably have fever which can be caused by any other infection off course.

00:14:56: You could have cough or sputum production.

00:14:59: again symptoms are very nonspecific.

00:15:04: And there is another very interesting aspect in the invasive pulmonary ospeculosis if we think on classical risk patients, which are usually neutropenic patients.

00:15:17: So where the immune system is blocked and a specific way so that neutrophils are low for example when you get hemotherapy Then you probably have a very classical radiological picture.

00:15:33: So if your radiologist sees the inflammation at a lung, then he probably gets an idea that this could be invasive aspergillosis.

00:15:44: but for example patient who is not neutropinic and in another way immunosuppressed having a severe influenza infection receiving intensive medical care, then these patients are also immunosuppressed.

00:16:05: But in this case if you're non-neutropenic immune suppressed... Then the radiological picture is again nonspecific.

00:16:15: You don't have specific pattern.

00:16:18: that reminds an invasive aspergillosis So it's very unspecific.

00:16:22: It could be any pneumonia.

00:16:27: Again, it shows how difficult is to get the idea that it could be an aspergillosis.

00:16:33: So in a clinical setting often really difficult and listening to podcasts like this probably creates more awareness.

00:16:42: so these help us think about dangerous disease.

00:16:47: It's relatively hard to diagnose.

00:16:49: but going back to mortality rates... How does that look once its diagnosed?

00:16:56: call this modality rate, maybe we should use the correct term of case fidelity.

00:17:01: But how does it look?

00:17:02: What's the outlook for a patient who has

00:17:04: that?".

00:17:06: Yeah if your patient receives the correct treatment early and you may be can also reduce to the grade of immunosuppression then the survival rate is quite good.

00:17:21: yeah but If you delay the diagnosis or if a patient is heavily immunosuppressed and cannot influence their immune suppression, then mortality is quite high up to forty percent or even higher.

00:17:34: So treatment of choice are ASALs.

00:17:36: so this is VORI connoisseur or ESAVU connoiseur for example these two drugs which are first line drug.

00:17:45: If you have an ASAL resistance for example aspergillus it's resistant then the mortality, of course increases far beyond the numbers I have told before.

00:17:58: The mortality for example is probably very comparable to the invasive form but a factor time is different.

00:18:08: so as i said before the chronic infection develops within months or even years quite a big systematic reviews and meta-analysis showed in mortality, twenty to forty percent which is also very high but within the next five years.

00:18:32: So almost half of your patients probably have a risk to die in the next six years Which not easy to communicate.

00:18:40: And problem with this case that treatment even more difficult than chronic pulmonary spitalosis compared to invasive form.

00:18:49: Because, as I said before when you have a timely diagnosis of invasive pulmonary sputulosis and the correct treatment.

00:18:57: And everything works well then you heal the patient so they can survive and hopefully no other health problems afterwards.

00:19:07: but in the chronic infection we are not able to heal or receive cure with the treatment.

00:19:17: We also give ASALs for quite a long time, six months to one year or even longer depending on tolerance of medication because it has quite a lot side effects and adverse events but we are not able to cure patients.

00:19:35: so this is completely different situation.

00:19:47: Going back a little bit again to the risk factors, right?

00:19:50: You mentioned already number of risk factors.

00:19:52: A suppressed immune system.

00:19:53: that can happen for many different reasons.

00:19:56: Malignancies are treated and lead to a suppressed immune systems.

00:20:02: Previous infections I guess you mentioned influenza probably other lung infections too.

00:20:10: what else is a risk factor.

00:20:12: I know there's something with previous tuberculosis that also sets you up for aspergillosis, could you talk a little bit more about who actually should be aware of this and very careful when thinking of aspergilose?

00:20:30: Yes so it's very important to differentiate the two infections.

00:20:35: So they invasive aspergyloses are course at their risk factors in immunosuppression And the highest risks have patients with a neutropenia, so patients who are heavily immunosuppressed.

00:20:52: So they have the highest risk.

00:20:54: and then it's not black-and-white.

00:20:59: it always depends on the grade of immunosuppression.

00:21:06: The higher, the immune suppression.

00:21:08: they're high at a risk to develop invasive pulmonary sputulosis.

00:21:12: for the chronic pulmonary Sputuloses It's typically this setting of structural damaged lungs or any lung disease.

00:21:22: Any respiratory disorder which destroys the lung may possess the risks of chronic aspergillosis.

00:21:32: so As you mentioned before, tuberculosis is one of the big players concerning infectious diseases worldwide.

00:21:42: So we have very high prevalence rates and this is an infection of lung usually or typically And it always... not always but very often destroys lung structure.

00:21:58: You also have residual cavities for example.

00:22:03: When you then inhale the spores and the conedia, Then you have to risk to develop a chronic infection.

00:22:09: But as I said before usually it can be any disorder Any respiratory disorder As long as It damages the lung than You Have A Risk To Develop The Infection.

00:22:22: And i guess smoking doesn't help either right?

00:22:24: Yeah Smoking of course.

00:22:26: if you develop a COPD in the lung emphysema Than you'll probably have quite then you have a risk to develop the chronic infection.

00:22:34: And it always depends on little bit of this setting.

00:22:38: where are, for example we did study in the north Germany and in a lung hospital... ...and of course that vast majority of patients included were patients with COPD.

00:22:51: So in these settings COPD was most relevant risk factor developing CPA.

00:22:59: But if you look, for example in other countries where the prevalence of tuberculosis is high then this is of course the highest risk factor and that's also a reason we have quite high CPA numbers or quite high number of chronic pulmonary sputulosis.

00:23:17: In countries were there are also a high prevalence of Tuberculosis.

00:23:22: This sounds dangerous because it sounds problematic.

00:23:28: If you're a person who has some of these risk factors, what can be done to protect yourself from the infection?

00:23:34: Which seems difficult because spores are everywhere.

00:23:39: Yes that's right and so one hundred percent protection is probably not possible Because as I said before every one of us is inhaling the spores on daily basis.

00:23:52: but if we do something where high risk to inhale a lot of spores.

00:23:59: So for example, you do some garden work with the composts or cleaning your garage and have quite a lot dust around then it would be good idea to wear mask which probably reduces number of inhaled spores.

00:24:17: so we hope at least that it reduces the risks to develop one diseases.

00:24:26: such special situations could be some kind of prophylaxis or to reduce the risk at least.

00:24:33: Also helps you not get hunter-virus infections, for example!

00:24:37: It's also good in waning viral diseases... You mentioned already treatments right?

00:24:44: And it seems that treatment options are relatively limited.

00:24:47: they come with side effects.

00:24:49: what do we see on the horizon and the pipeline for better treatments?

00:24:56: His treatment of fungal infections was quite challenging in the past, or it still is.

00:25:01: But in the Past we just had three classes of antimicotics so these were the ASALs, the achinocondins and the amphotericine B. but now we are lucky because last year there's been a lot of studies going on with different classes also developing classes and there are quite a lot of study phase two studies in phase three studies.

00:25:28: For example, resa fungion.

00:25:30: this is new medication which given intravenously with you give once per week.

00:25:37: And it's interesting because if your treat patients for example with echino-candins for different fungal infection or Candidemia then usually do these on word but With resa function, for example you could do this also in an outpatient setting.

00:25:56: And this drug is at the moment In a phase two trial or it's now It's a phase-two trial ongoing Now For chronic palmonary sputulosis and resa fungion.

00:26:10: I'm really looking forward to the results because This Could be another new treatment option for CPA patients.

00:26:17: And then there are quite interesting new substances like Fosmanocipics, another new antimicotic which again you could do or you can treat patients with an yeast infection.

00:26:31: With Candidemia for example but also maybe from moles.

00:26:35: so For both indications There face three studies ongoing at the moment.

00:26:41: So hopefully in next one or two years we will see results of that.

00:26:47: So this is a very promising time at the moment for antifungals because we are getting new drug classes and new drugs within known classes.

00:26:59: I think it will become more exciting in next years!

00:27:04: It's nice to hear that there is positive outlook, movement right?

00:27:09: There seems lot of improvement so thats great.

00:27:12: Maybe one last question When was this disease recognized, right?

00:27:18: Is it something that's a new development and we start to see these now in the last few years?

00:27:22: or is there something has always been there.

00:27:25: What's the history of...

00:27:27: Yeah actually its not a new pathogen.

00:27:31: We learn quite a lot in the past year so It's becoming more exciting.

00:27:36: but The name Aspergillus dates back to seventeen twenty nine.

00:27:42: So it's not a new pathogen.

00:27:45: It was actually described by an Italian naturalist, the name was Pierre Antonio Micheli and he saw the aspergillus under the microscope.

00:28:01: And this structure reminds him of Aspergilium which is a holy water sprinkler.

00:28:12: So it looks like this hollywood, the sprinkler which you can see in The Church.

00:28:16: And that's why it is called Aspergillus.

00:28:21: Okay!

00:28:21: That's an interesting story.

00:28:23: and when was the disease first described or what?

00:28:27: When were there connections between the pathogen and diseases?

00:28:32: Actually the first description of a human palmonary aspergillosis was in the nineteenth century.

00:28:41: So this was a case of a patient, so around eighteen forty-seven if the number is correct but I'm not sure about that.

00:28:51: This was a pathologist and in their resection he saw as Aspergillus fungus in the lung... ...so these were the first descriptions of disease caused by Aspergilus.

00:29:04: But they names.

00:29:05: what we have now are understanding that we're having invasive Asperigilluses And the chronic, this was just described in the last decades.

00:29:16: So especially the chronic palminar espicillosis is something which we have learned in the past years to be honest because it's not only a fungal ball... ...which was the first description of the nineteenth century.

00:29:32: but for example the chronic pulmonary espicilosis can Look completely different.

00:29:37: It can also be just noddles in the lung or it can be a thick walled cavity and this was not understood couple of years ago, so really something which we have learned last let's say twenty years.

00:29:53: This is super interesting very important to raise awareness for these diseases and maybe encourage more research into diagnostics, it looks like with therapeutics we're in a good way but I think more research will also be helpful there.

00:30:11: So Helmut...I don't know if you have any other points that you want to make?

00:30:16: Any other information?

00:30:21: I think the most important thing is to be aware of these fungal infections.

00:30:25: Also, clinicians because somehow this is still a neglected disease.

00:30:32: It's quite hard word neglected and you do not find as much as on the WHO neglected diseases list.

00:30:41: but in clinical setting i really have feeling that it is somehow neglected.

00:30:46: so I would be very happy if we can insert an idea to some clinicians, think a little bit more often on these interesting aspergillus infections.

00:31:01: Thanks a lot Helmut for your time today and talking with me about aspergilosis is fascinating.

00:31:08: also find it scary.

00:31:10: this is more scary than viral infection.

00:31:17: Again, good to hear that we are on a positive way in terms of therapeutics.

00:31:22: So thanks again for joining and as always if people have comments questions or suggestions please write an email to Virological at podcastwerkstatt.com.

00:31:35: This time I probably send this forward these emails to Helmut because i don't know much about Aspergillosis and he is the expert.

00:31:43: but again reach out if you have any And if you want to support our podcast, You can do that on Steady.

00:31:51: Thanks a lot for listening in and until next week!

00:32:31: Bye.