Weakened immune systems leave people vulnerable

[00:00:00] Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. "The Last of Us" was a TV series about life in a post-apocalyptic world during a rapidly spreading pandemic caused by a fungus. While the TV show was fictional, the threat fungi posed to humans is real -- and on the rise. Here to explain is Dr. Ramiro Gutierrez. He's an assistant professor of medicine and deputy chief of infectious disease at Upstate. Welcome to "The Informed Patient," Dr. Gutierrez.

[00:00:41] Ramiro Gutierrez, MD: Thank you very much. Happy to be here.

[00:00:43] Host Amber Smith: The outbreak on "The Last of Us" was caused by cordyceps. Is that a real fungus?

[00:00:49] Ramiro Gutierrez, MD: It is, it is. And I did not know much about that show before my kids asked me about it and asked me a similar question. But, yes, there is a real, based on a real fungus that infects insects, as I understand it.

[00:01:04] Host Amber Smith: So it infects insects. What does this fungus do?

[00:01:08] Ramiro Gutierrez, MD: So cordyceps I think has fascinated people because, certainly, of the show and nature documentaries. But it is a relatively quite specialized invasive fungus of really very simple organisms, so ants, insects, perhaps spiders. And it's very specialized to infect that type of animal, which obviously is quite a simple organism compared to people or mammals.

[00:01:33] Host Amber Smith: Does it make the insects sick?

[00:01:36] Ramiro Gutierrez, MD: It does. And it has an interesting mode of spread in that these insects that have become infected with this organism tend to behave differently once they are infected and seem to move to high ground and then, at that point, become disabled. And this fungus germinates. So it seems to use these organisms, these insects that they infect, to spread. So it, it changes their behavior a little bit.

So I think that's where the show and the science fiction show kind of took on that aspect that it's the fungus that makes the infected host behave in a different way. But again, these are very simple insects, ants, that have become infected, and the behaviors that the fungus causes are quite simple as well.

[00:02:26] Host Amber Smith: On the TV show, this mutated form of cordiceps begins infecting humans. Is that something that could happen in real life?

[00:02:35] Ramiro Gutierrez, MD: You know, I think in infectious disease we've learned to be humble about organisms and how they can mutate and change in several ways. But, frankly, this is probably in as far as that show goes, and the game, that's where science fiction kind of comes in.

These cordiceps fungi that you mentioned are very specialized to infect very simple organisms. And you don't see this type of behavior or manifestation in more complicated mammals and so on. So I think it's probably unlikely for humans to experience something like it's depicted on the show, and probably not. These are not the fungi that keep me up at night and worry me as far as human infections. But it's an interesting idea and certainly fascinating from a science fiction perspective.

[00:03:22] Host Amber Smith: Well, let's talk about how a fungus differs from a bacteria or a virus. Which of these organisms is the biggest threat to humans, and why?

[00:03:33] Ramiro Gutierrez, MD: Well, I think they're all threats in different ways. But probably in most simple terms, viruses are the simplest of all these infectious organisms, or infectious agents. Bacteria are a little bit more complex. And fungi are probably even further, more complex and more similar in some respects to humans and human cells.

They vary. So they're all big problems in their own way. We saw Covid being a virus, being quite a significant and impactful infection worldwide. And so can bacteria and fungi, just in different ways.

[00:04:09] Host Amber Smith: Does one spread faster than another, necessarily?

[00:04:13] Ramiro Gutierrez, MD: It's variable. I think viruses are known for their ability to spread rapidly, whereas bacteria, perhaps, have a, depending on the organism, they can splint pretty rapidly as well. Fungi are present around us constantly. I think that's an important thing to remember, and many of these fungi that are important for human disease are fungi that we live with every day and we're exposed to almost daily. The humans who become infected with these that are more medically important often have some vulnerabilities. So that's kind of a key aspect here. For invasive fungal infections in humans is that we're actually pretty good at fending off these infections and invasive disease from a fungus. But most of the folks affected have some vulnerability, some immune defect, some medical intervention that's made them vulnerable and such that make them more likely to be infected. So, it's a little bit different than some of these other infections.

[00:05:15] Host Amber Smith: So how do fungi infect humans?

[00:05:19] Ramiro Gutierrez, MD: Well, like I said, a lot of these, the ones that are medically important -- and it's a short list of most important medically invasive fungi -- like I said, in many instances are around us or live on us. Some of these are yeasts that are normal, form part of our normal microbiome that exists in us. But when individuals become vulnerable, that is, they're sick, they're in the hospital, they have devices, perhaps, to help them treat their condition. Maybe they're intubated in an ICU, or they're having therapies, like cancer therapy or bone marrow transplants, things to treat an underlying condition. Those things make them vulnerable to these fungal organisms to then get into places where they shouldn't be and cause infection, serious infection.

[00:06:09] Host Amber Smith: Once somebody is infected with fungi, can they spread it to other humans?

[00:06:15] Ramiro Gutierrez, MD: Some of these fungi live in the environment, so they are already present in soil and so on. Depending on the fungal infection, some are found in hospitals and, again, healthcare facilities, where there are patients who are, again, vulnerable and susceptible to these infections in those environments. There could be spread in the environment. So there are infection control and other methods that are used to prevent the organisms from spreading. But, they are often present in the environment.

[00:06:48] Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith. I'm talking with Dr. Ramiro Gutierrez. He's an assistant professor of medicine and deputy chief of infectious disease at Upstate.

Why is the risk of fungal infections, in general, on the rise?

[00:07:06] Ramiro Gutierrez, MD: There's a few factors. So, vulnerable hosts or people, individuals who are vulnerable to these infections, that population has grown. So certainly in a resource-rich setting, a place like the United States where, if you are diagnosed with a serious illness like cancer or require a complicated surgery that may require you to stay in the ICU for a prolonged period of time, those therapies are available.

But those therapies also make you vulnerable to some of these fungal infections. So in a country like ours, I think it's an indication of the ability to treat folks with very serious illnesses and getting them through those periods of time where they are very weakened, from an immune standpoint or a surgical standpoint. I think that's one factor.

The preponderance of the ability that we have now to treat serious bacterial infections and using a lot of antibiotics in very broad spectrum, or antibiotics that can have activity against a lot ofgerms and organisms, bacteria, also results in fungal infections going up as well.

So I think in our setting, those are some of the drivers. In resource-poor settings, places outside the United States where there is still problems with H I V infection, which also makes people immune compromised, and perhaps even climate change effect has been associated with different sets of invasive fungal infections as well.

So I think it's multiple factors. And here in our setting in the United States, probably one of the largest is probably that we provide very advanced medical care and are able to take care of people who have weakened immune systems and are very vulnerable to these infections.

[00:09:00] Host Amber Smith: Does climate change impact fungal disease at all?

[00:09:03] Ramiro Gutierrez, MD: There are ideas that it probably does for certain fungal diseases. So there are some fungal infections that are invasive, which are driven by fungi that are in the environment, for instance, soil and the outdoors may be associated with certain situations where humidity and heat and rain patterns can change the relative abundance of these fungi in the environment. So that's one instance where there is some probable effect of climate change.

[00:09:41] Host Amber Smith: You mentioned antibiotics. Are antibiotics used to treat fungal infections?

[00:09:48] Ramiro Gutierrez, MD: The word antibiotic, in general, refers to pharmaceuticals that affect bacteria. So antifungals is the general term we refer to for drugs and agents that are specific to fungi. They are quite different. Fungi, are, like I said earlier, a little more similar to humans in terms of our cell machinery. Bacteria are quite different. So it is, perhaps, a little easier to make antibiotics against bacteria because they have a number of, if you will, targets in their cells that are different than ours. An ideal antibiotic or antifungal, or antimicrobial for both, are drugs that would not affect the person, and it would just target the infecting organism. So fungi, being a little more similar to us, we have a few less targets to go after. So that is a challenge to develop new antifungals.

But, to answer your question, yes, antifungals and antibiotics generally refer to very different types of drug.

[00:10:56] Host Amber Smith: The antifungals that exist, can they be used on more than one type of fungus?

[00:11:03] Ramiro Gutierrez, MD: Since the first antibiotics were developed, there's been quite a few antibiotics, many antibiotics, generated over time. Antifungals, there's a much shorter list of available drugs. For a very long time there were only three classes of antifungals, and for about 20 years there were no new ones until fairly recently when an additional class became available.

So they are specific to different fungal agents. But the list is frankly much shorter of different drugs that are available for fungal organisms, as supposed to bacteria, which we've been dealing with for quite a long time.

[00:11:41] Host Amber Smith: In healthy people, does the immune system effectively fight fungal infections? Is that part of how it's treated, is just by letting the immune system do its job?

[00:11:52] Ramiro Gutierrez, MD: Yeah. The immune system, the human immune system, is really exquisitely good at dealing with fungal infections. It's a very important protection from these infections. And, like I said earlier, I think one of the biggest changes that has led to us seeing more of these infections happens to be that there are just more and more patients that are vulnerable.

So their immune systems are affected in some way, in part due to their illness or the illness we're trying to treat. So the immune system is very important. Normally it's quite good at fending off these infections -- other than the common ones that people may experience, like athlete's foot and some of these superficial skin fungal infections. So invasive fungal infections like we're talking about here, generally our immune system is very good at protecting us, and usually we have to be vulnerable in some way to fall subject to it.

And indeed, although the antifungals are important and can be a critical piece of treating someone with these infections, remedying some of the immune defects or some of the other vulnerabilities and addressing those becomes an important part of the treatment as well.

[00:13:01] Host Amber Smith: In the vulnerable population, or someone with a compromised immune system, what are some of the most common fungal infections that you see that you treat in the hospital regularly?

[00:13:13] Ramiro Gutierrez, MD: Probably one of the most common are infections caused by candida, which is, within fungal infections, it's a yeast. We call it a yeast. Candida are yeast that live on us and in us. They are a normal part of our microbiome. Most of us have some candida. However, if you're quite ill, maybe you've received a lot of antibiotics, you've been in the intensive care unit, dealing with an illness or trauma, perhaps you're getting antibiotics to treat a pneumonia or something like that, then that candida that's within us can then become invasive and get into somewhere it shouldn't get, into the blood or somewhere else and cause a very, very serious infection.

Those types of situations are probably the most common we see in the hospital. And then there's a few others, diseases caused by another fungus called aspergillus. That one is an environmentalfungus that is, again, present in many environments. We're exposed to it probably daily. But again, certain very vulnerable populations can become infected with it as well. So those are probably among the most common.

[00:14:22] Host Amber Smith: So if someone is treated successfully for a fungal infection, does that protect them from future fungal infections from the same fungi?

[00:14:31] Ramiro Gutierrez, MD: These are more complex organisms, and the immune response to them is probably just as complex. Probably the answer is generally no. If you have been treated for one of these infections, you could be at risk for another one. But probably only if you become vulnerable again or that vulnerable state. Again, these are organisms that we come in contact with pretty frequently, if not every day.

[00:14:58] Host Amber Smith: Well, Dr. Gutierrez, I appreciate you making time for this interview.

[00:15:02] Ramiro Gutierrez, MD: Oh, absolutely. It was a pleasure talking to you.

[00:15:05] Host Amber Smith: My guest has been Dr. Ramiro Gutierrez. He's an assistant professor of medicine and Deputy Chief of Infectious Disease at Upstate. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at goudounet.com/informed. This is your host, Amber Smith, thanking you for listening.