By Dona Suri
Candida auris hit the headlines a couple years ago and went straight to the top of the Scary News List. It didn’t help that about the same time we were reading about it, HBO was airing a chiller-thriller called The Last of Us, about a fungus out to zombie-fy mankind. In the years that followed the initial discovery, medical sleuthing has compelled this fungal fiend to yield many of its secrets, so that we now have good news and bad news.
First, the GOOD news …
C. auris is not a serious threat to healthy people … so far.
C. auris is not yet widespread. Nearly all U.S. states have fewer than 100 cases of C. auris.
C. auris is relatively slow to mutate compared to viruses.
Medical researchers all over the world are studying C. auris to figure out how it works, how to diagnose it quickly and accurately, and how to deal with it.
Next, the BAD news …
C. auris has spread rapidly.
(Discovered in Japan in 2009. As of mid-2023 it had been reported in more than 50 countries on six continents. In the US, cases of C. auris skin colonization nearly tripled from 1,310 cases in 2020 to 4,041 cases in 2021, and case numbers rose again in 2022 and 2023*.
*Rapid increase in case numbers may point to …
Spread of the organism.
(May have been enabled by poor general infection prevention and control practices in healthcare facilities, especially those under strain during the covid pandemic.)
Awareness. Until recently, doctors were not looking for C.auris. If they saw it, they didn’t know what it was.
More screening to see if someone has the fungus somewhere on their body but does not have an infection. The more you screen, the more you find.
C. auris can grow on anything – living and non-living, skin, bed sheets, metal surfaces, plastic gloves, oxygen masks, etc.
C. auris can go for weeks without water and tolerates salt.
C. auris resists antiseptic cleaning solutions, including hydrogen peroxide, povidone iodine, and chlorhexidine.
C. auris is not incurable, but it is difficult to beat and requires high doses of multiple antifungal medications. It resists all known fungicides, including azoles, amphotericin B, and echinocandins.
C. auris is difficult to diagnose. Symptoms mimic those of many other infections. It most often strikes people who are already very sick with something else. Misdiagnoses leads to incorrect or belated treatment. Making a sure identification of C. auris requires highly sophisticated molecular-level analysis. Very few hospitals have the means to perform such tests.
C. auris mortality rate is high among people who are either very sick, have invasive medical devices, or have long or frequent stays in healthcare facilities.
C. auris has health authorities worried:
The Centers for Disease Control declares it an “Urgent Threat” and categorises it as “Most Serious”.
The World Health Organisation expresses “Critical Concern” and places it Number 1 on its “Fungal Pathogen Priority List”.
From the perspective of the immediate medical challenge, C. auris is bad enough, but it is even more alarming to think about the emergence of this fungus in the context of a rapidly warming plant and escalating damage to the environment.
Back in 2019, before the alarm bells really started clanging in the CDC and the WHO, mycologists were pouring over reports about C. auris and seeing nothing but question marks.
An opinion piece by Drs Arturo Casadevall (Johns Hopkins), Dimitrios P. Kontoyiannis (MD Anderson Cancer Center, University of Texas) and Vincent Robert (Westerdijk Fungal Biodiversity Institute, Utrecht University) in ASM (American Society for Microbiology) Journals of July 23, 2019, wrestled with the big question: how and why had C. auris emerged and how had it acquired its capacity to make humans sick. Their essay, titled On the Emergence of Candida auris: Climate Change, Azoles, Swamps, and Birds, concluded
If anything, the direct and indirect effects of climate changes induced by an exponentially growing human population as drivers of fungal evolution should be an area of intense research in the decades to come.
The writers contemplated several interconnected issues.
First of all, “emergence”:
Analysis of C. auris samples collected from the Indian subcontinent, Venezuela, and South Africa between 2012 to 2015 revealed that the samples from each continent were clonal, but that those from different continents constituted genetically different clades.
How was it possible for C. auris, as a human pathogen, to emerge simultaneously on three continents, with each clade* being genetically distinct?
* Clade: a group of organisms that consists of a common ancestor and all of its descendants.
C. auris is both fungicide-resistant and able to cause disease in humans.
This species might have evolved in response to widespread use of fungicides in agriculture but that does not explain why it suddenly became a human pathogen all over the world.
Was C. auris a human and animal pathogen first and afterwards it acquired drug resistance?
Or, did C. auris develop resistance to fungicides and virulence (ability to make humans sick) at the same time?
The authors noted that virulence does not evolve in a quick, straight, simple way, driven by just one factor. They reasoned that if drug-resistant, virulent C. auris popped up on three continents at the same time, there had to have been some global, major cause pushing it.
That brought them to “climate change”.
All mammals and birds generate internal heat; that’s why they are called “warm-blooded”. Normal temperatures for mammals range between 97° F to 104° F; normal bird temperatures are higher: between 106° F and 109° F.
Fungi grow in dark, moist, cool places. Mushrooms (fungi) do best in rooms cooled to between 65-75°F and most fungi species like it even cooler.
Mammal bodies beat off invasive fungal diseases simply be being too hot. (Plus the immune system attacks fungal cells.) The difference between their high body temperatures and environmental temperatures is what protects mammals from fungal invasion. This is called the Thermal Restriction Zone.
Dr Casadevall makes a strong argument that fungi were instrumental in the emergence of mammals as the dominant large animals.
[Fungi and the Rise of Mammals, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420938/ Synopsis: Asteroid impact circa 66 million years BCE -> sky darkened by dust, smoke for months > vegetation dies -> dinosaurs starve, fail to reproduce -> fungi thrive on cool, dark earth -> warm-blooded mammals, immune to fungal infection, survive and take over.]
Human activity is causing temperatures to rise all over the world. The difference between mammal body temperature and ambient temperature is getting less and less. Some fungi species evolve to become heat tolerant to such an extent that they can breach the mammalian Thermal Restriction Zone. Researchers have already observed this in laboratory experiments.
It’s happening outside the laboratory too. The authors noted that “many fungal species that are currently nonpathogenic species are likely to have the necessary virulence attributes by virtue of their survival in soils.”
But the writers were not entirely satisfied with the “climate change” explanation. It didn’t account for how four clades of C. auris strains emerged spontaneously … and that too in geographically disparate regions, each separated by thousands of years of evolutionary distance from each other. The writers were looking for a convincing answer as to how a fungus – whose original habitat was probably a bog, and who was least interested in human bodies – jumped up to an all-over-the place fungus that makes people sick.
They threw a wide net to find the answer: genes involved in production of enzymes shared by all four clades, mating of different species if geographically isolated species were brought together by inadvertent human transport or migratory bird patterns. (Mating fungi? Who could have guessed?)
When they listed factors that might have contributed to the emergence of virulent, drug-resistant fungi species. the list was not only long but speculative: high human population densities, migrations, increased urban temperatures, poor hygiene, pollution, regional and international travel. The writers confessed that finding solid evidence linking these factors to the emergence of C. auris would be difficult but necessary.
The authors provided a highly technical description of C. auris and specific genes behind its multidrug resistance, virulence, thermal tolerance, and osmotic-stress tolerance and made some educated guesses about the original habitat of C. auris and the means by which it broke out. (This is the “swamps and birds” part of the paper’s title.)
A tangential but interesting point concerned C. auris’ choice of victims. People who were already seriously ill were the most vulnerable. While the vulnerability was cruel from the perspective of the affected individual, it was useful for researchers.
“Because their debilitated conditions impair their immunity, this group may serve as sentinels for the appearance of new fungal diseases.”
When it comes to detecting the presence of C. auris, sick or immune-compromised individuals are the canaries in the coal mine.
The authors remained wary of conclusions.
Could the emergence and transformation of C. auris be blamed climate change?
Did other explanations, other trajectories, produce more satisfying maps of C. auris’ journey into the realm of human-pathogenic fungi?
They were not shy about saying that while C. auris is the first example of a new pathogenic fungus emerging from human-induced global warming, it would not be the last.
If climate change is the driving factor, then obviously more deadly fungal species are on the way. What chance do medical researchers have in the face of an environmental shift? By the time they have figured out how to defeat one new virulent fungi species, another, perhaps more virulent, species, emerges. A never-ending game of whack-fungus does not look like the way to go.