Why Fungal Diseases Are an Increasing Threat
As fungi adapt to warmer temperatures and develop resistance to drugs, we need to bolster our defenses.
The internal temperature of humans (98.6F and 37C) provides strong protection against fungal disease, as does a well-functioning immune system. But what happens when fungi adapt to a warming world?
We can expect fungi to become more successful in surviving and reproducing in our bodies, says Casadevall, MD, PhD, a Bloomberg Distinguished Professor and the Alfred and Jill Sommer Professor and Chair of the W. Harry Feinstone Department of Molecular Microbiology and Immunology. In fact, he believes we’ve already witnessed the emergence of the first fungus to overcome our body’s thermal defenses—Candida auris. (Casadevall’s thoughts on C. auris were captured in a 2020 Radiolab podcast memorably titled, Fungus Amungus.)
In this Q&A, Casadevall, who was recently elected to the National Academy of Sciences for his work on fungi, explains why we need to take a more serious approach to fungi, long dismissed as a nuisance cause of dandruff or jock itch, and begin developing antifungal vaccines and treatments now.
Certainly with the pandemic, viruses are front and center. Bacteria and parasites also get lots of attention, but fungi not so much. Why is that?
The reason for that is because you are probably not afraid of the fungi, right? We tend to get fungal diseases in daily life—you can get nail infections, you can get athlete's foot, dandruff. Those are all fungal diseases, but none of them are life threatening.
Fungi are the major pathogens of plants. They are the major pathogens of many insects. They are devastating frogs. So, the question is, what makes us so special? And then why have fungi only become major problems in medicine in the late 20th century?
If you had visited Johns Hopkins Hospital in the year 1900, or even 1922, you would have not seen fungal diseases. Well, what happened is that we changed as a result of medicines that extend our lives at the price of immunity.
You’re talking about drugs that suppress the viral load of people with HIV, for example?
Yes. As we began to see more immunosuppressed individuals, we began to see more fungal diseases, and these fungal diseases are very difficult to treat because we have very few antifungal drugs.
You have a class of organisms that was not a major problem become a major problem.
Why weren’t fungal diseases a big concern?
Our resistance is coming from two pillars. One pillar is our advanced immunity. The other pillar is we are hot. Our body temperature does not create a hospitable environment for fungi. The majority of fungal organisms simply cannot replicate at body temperature. And then you add that powerful immune system, and we don't usually have a problem with fungi.
Because we don't worry about the fungi, not a lot of work is done with the fungi. So, we don't have too many drugs. We don't have any fungal vaccines, and it all becomes kind of circular.
What are some of the big fungal diseases we should know about?
If we get hospitalized, or if we take immunosuppressive medications, the big diseases that we need to worry about would be something like Candida. People with HIV get oral thrush. People in the hospital who get IVs tend to get Candida infections in the blood. If people become immunosuppressed for a long time, then they have to worry about some of the spores that they breathe in. That brings in Aspergillus.
It's a common problem in transplantation. A lot of progress has been made in transplantation, as we made in cancer, but that often has come at the price of immunity. And those individuals are now at high risk for a variety of fungal diseases.
As a species, we're not really good at appropriate preparation. We react. We were not selected in evolution for long-term planning.
You’ve talked about how our internal temperature can protect us against fungi. What about changes in external temperature—from climate change? How will that change the fungi-human dynamic?
As the world is getting warmer, the fungi will have to adapt. Every hot day is a selection event. If your sidewalk goes to 120 degrees, the [fungi] that make it to 120 degrees will survive.
That brings me to another story. Candida auris is a fungus unknown to medicine until 2007, when it gets recovered from somebody's ear. Then, a couple of years later, it emerges as a major pathogen for immunosuppressed people in three continents at the same time—in South America, Africa, and India [Asia].
So, the question I posed to everybody is, how could you end up with something appearing at the same time in three different continents if these organisms are unrelated? I have argued that that is the first example of a fungus that is breaching our thermal defenses. And that fungus has already come in drug resistant.
If you have a fungus that today can grow in, let's say, 34 degrees [C], it can cause disease in insects and it can cause disease in plants. But it can't get into you because you're too hot. But you know what? After about three really hot years, maybe it could hang on at 37 degrees [C].
Meaning it could get past our thermal defenses and survive in the human body?
You're going to have a problem that you didn't have before.
Does this add special urgency to your research?
That’s what I tell everybody. Sadly, Brian, as a species, we're not really good at appropriate preparation. We react. We were not selected in evolution for long-term planning.
But your argument is that this is happening now. It’s time to react.
Exactly. We need to react, and we need to develop new antifungal agents.
No, I think humanity will win. We are remarkably resourceful, and we will have kind of figured it out. And if you need any evidence of our resourcefulness, look at the COVID pandemic and look what was accomplished in two and a half years scientifically.
So, I'm very optimistic. I really am. The fungi—they're a tremendous threat for humanity. But I also think that we have tremendous resources, and we are very inventive and creative.