Cadida auris, is a fugus that is “pretty much unbeatable and difficult to identify,” and which the CDC says causes nearly 50% of patients to die within 90 days. It has an overall mortality rate of 30%-60%. If you get this thing, it is very likely that you will die before they have even figured out what you have. And it’s so persistent that after you die, the hospital has to tear out the ceiling tiles to fully rid the hospital of the fungus:
Tests showed it was everywhere in his room, so invasive that the hospital needed special cleaning equipment and had to rip out some of the ceiling and floor tiles to eradicate it.
“Everything was positive — the walls, the bed, the doors, the curtains, the phones, the sink, the whiteboard, the poles, the pump,” said Dr. Scott Lorin, the hospital’s president. “The mattress, the bed rails, the canister holes, the window shades, the ceiling, everything in the room was positive.”Source
That last part about tearing out the ceiling tiles is what made me rewind the article as I listened to it back in April. Hospitals have had to shut down entire wings and even close entire hospitals because of C.
From this gem of
an observationgrew one of the most curious aspects of our series: The rise in resistant bugs is cloaked in widespread and chronic secrecy.
As our reporting continued, we discovered it was common for hospitals, doctors and public health agencies to clam up when it came to talking about their troubles with resistant bugs, though they widely acknowledged the existence of the problem and even encouraged our efforts.
We came to realize that the secrecy surrounding C. auris was a big part of the story. A doctor in Spain wrote me that the hospital didn’t want bad press by seeming to be a hotbed of the fungus. I got the same message from a doctor in England. One doctor in New York told me that patients, and their families, don’t like being associated with the illness, as if they had a scarlet letter — “A” for auris.
Even with the secrecy, I knew I would hear about C. auris again some time soon. Since its discovery in 2009 on a Japanese man’s ear (named Auris from the Latin for “ear”), it reemerged in humans again a few times between 2012 and 2015, and what was remarkable is that it happened pretty much simultaneously on three separate continents. The worst part was that all three of the strains were genetically different. So not only is this fungi resilient and spreading, but there are actually multiple strains with different evolutionary lineages that can infect humans (pathogenic). That tells us this is something systemic is going on, not just something locally, and that this is a global problem.
This also isn’t one of those cases of a pathogen emerging from thawing permafrost. Those are an entirely different nightmare of a problem, an example of which happened during a heatwave in Sibera in 2016, when a herd of reindeer that had died from anthrax decades earlier and frozen under the tundra, thawed out and transmitted the bacteria to humans. Ultimately, they had to kill 250,000 reindeer to halt the spread. While that is of great concern and also keeps me up at night, it is not even in the same league as the systemic problem of fungus being more able to survive inside humans.
The first hypothesis I heard, as proposed in the in NYT article on the secrecy at hospitals, stated that the cause might be from the increased use of fungicides to treat crops. A man in
The theory had been that the excessive spraying of fungicides on plants, such as potatoes, beans, wheat, tomatoes, etc caused and increase in drug resistance. The theory, as the head of the fungal branch at the C.D.C, Dr. Chiller, stated to the NYT, went something like this:
C. auris may have benefited from the heavy use of fungicides… C. auris actually has existed for thousands of years, hidden in the world’s crevices, a not particularly aggressive bug. But as azoles began destroying more prevalent fungi, an opportunity arrived for C. auris to enter the breach, a germ that had the ability to readily resist fungicides now suitable for a world in which fungi less able to resist are under attack.
While this theory is in some ways plausible for other strains, other research points to a different, much more worrying process for the evolution of C. auris and other salt marsh fungi. The new study suggests that Climate Change may actually be to blame. By becoming more able to counteract the effects of a warmer ecosystem, fungi are now able to overcome one of the major defense system of our body, a high average body temperature and even warmer temperatures when we have a fever.
Check out the chart below of the thermal tolerance of 40,802 fungal strains from 144 genera. Most of them cannot grow at mammalian temperatures and therefore, automatically gives us resistance. The normal human body is 36.5-37.5 °C (97.7-99.5 °F), but during a fever goes up to 37.5-38.3 °C (99.5-100.9 °F) and higher. In the chart below, the “squares” show 49 mammal core temperatures. The higher position of the “square” on the chart equates to a greater percentage of mammals whose bodies are in that temperature range. You can see that towards the right of the graph, around 35 degrees °C, fungi can no longer easily survive. It has been posited that this is not a coincidence, and is known as the “thermal exclusionary zone” and, as will be discussed below, may have even been the adaption that allowed mammals to come to dominate the planet in the face of fungal infections.
While the theory on the increased resistant of fungi to pesticides holds some validity, in this case, it appears something much more sinister and foreboding is at play. The theory doesn’t make complete sense in this case because C. auris appears to have emerged independently on three continents simultaneously: the Indian subcontinent, Venezuela, and South Africa.Further, the emergence of azole-resistant Candida began long before the appearance of C. auris and there appears to be no correlation to the emergence of the azole-resistant Aspergillus that was mentioned above. In addition, simply acquiring drug resistance, while making the fungi harder to kill, does not necessarily make it evolve to become pathogenic. Normally, a fungi would be known as a pathogen, then treated, then it would evolve drug resistance, instead of acquiring drug resistance from agricultural fungicide use first, then somehow evolving to become a pathogen.
Something else had to be at play then and a new paper titled “On the Emergence of Candida auris: Climate Change, Azoles, Swamps, and Birds,” posits that Candida auris’ rise is the “first example of a new fungal disease emerging from climate change.Think about that chart above that shows fungi unable to survive at higher temperatures. As the Earth becomes warmer, the fungi are evolving to survive at these higher temperatures. Those higher temperatures of the planet are now getting closer to and in some places surpassing the temperature of the human body (37.5 °C), essential threatening our body’s fungal immunity and closing our “thermal restriction zone” that prevents us from being infected.
“[A]s the climate has gotten warmer, some of these organisms, including Candida auris, have adapted to the higher temperature, and as they adapt, they break through human’s protective temperatures”
Co-author of the new study, Dr. Arturo Casadevall, chairman of molecular microbiology and immunology at Johns Hopkins University, said the above, and in his paper. I personally was unaware how strongly the effects of our warmer bodies was on preventing fungal infections until doing the research for this article.
In fact, there is an entire body of evidence on how the “thermal exclusionary zone” allowed mammals to surpass dinosaurs as the dominant species on Earth! The theory is called the “Fungal Filter,” and states that as Earth transitioned from the Cretaceous to the Tertiary period, a time known as the K-T boundary, that mammals became the dominant earth
To follow up on this theory, researchers point to the existence of fungal infections in mammals that are opportunistic, in both humans with compromised immune systems and in bats that lower their body temperatures during hibernation. Humans with HIV have high incidences of fungal infections such as oral Candida
“The white-nose syndrome in bats occurs during their hibernation process, when their temperature drops. The thermal restriction zone that protects mammals is the difference between their high basal temperatures and the environmental temperatures. Human-induced climate change is anticipated to warm Earth by several degrees in the 21st century, which will reduce the magnitude of the gradient between ambient temperatures and mammalian basal temperatures. Consequently, there is concern that higher ambient temperatures will lead to the selection of fungal lineages to become more thermally tolerant,such that they can breach the mammalian thermal restriction zone.
The really bad news here is that even if we don’t have lower body temperatures or compromised immune systems, fungi have been shown in directed evolution studies to be able to fairly quickly adapt to higher temperatures through a process called thermal selection. As cities are hotter than the surrounding areas due to the “heat island effect,” by comparing the same species of fungi in both in rural and city locations, scientists were able to clearly demonstrate fungal thermal selection, with the urban strains being more resilient to higher temperatures:
So knowing that warmer climatic conditions can cause the evolutionary selection for fungi that can withstand warm temperatures, Casadevall
In the chart below, the color green represents temperatures that a fungus can stay alive at and red where it is cannot. I scaled the image from above so that you can see the temperature at which fungi can no longer survive
C. aurisis an ascomycetous yeast and a close relative of the Candida haemulonii species complex, which includes species occasionally pathogenic in humans and animals and demonstrates a high level of baseline antifungal drug resistance. This phylogenetic connection may explain its low susceptibility to antifungal agents and the possession of virulence attributes that confer it with pathogenic potential.
They also note that because the first case of C.
So you can see it for yourself, here is where the
With this background, we propose the hypothesis that Candida auris is the first example of a new pathogenic fungus emerging from human-induced global warming. We posit that prior to its recognition as a human pathogen, C. auris was an environmental fungus. The fact that C. auris fails to grow anaerobically, along with the fact that it is typically detected on cooler skin sites but not in the gut, supports the notion that C. auris was an environmental fungus, until recently…
Candida albicans is a different strain of Candida that is drug-resistant and pathogenic to humans and is typically found in the stomach. It
So the danger is that in the wild, various fungi can share the genetic material that provides fungicidal resistance. As the study on plasmid transfers between yeasts states in its conclusion, we aren’t even sure how they do this:
Although sexual activity between C. glabrata and S. cerevisiae cells has not been observed previously, we observed a relatively high frequency of transfer of genetic material between these yeast species. The mechanism(s) for this transfer is not clear… The transfer observed could allow the spread of virulence factors and resistance to medical drugs even between distantly related yeast species and could probably help in the “transformation” of harmless saprophytes into potential causative agents of human infections.
So basically, fungi have methods to transfer genetic material between themselves and so other types of fungi that are resistant to our drugs. When those fungi survive and make it through our sewer systems, they can then transfer those newly acquired abilities of resistance to the fungi that have been evolving thermal tolerance and structural resiliency to the salinity in marshes, basically becoming breeding pools of
In the past, isolated fungi
Here is an overview of a proposed process, followed by a graphic summarizing how the researchers suggest the spread of C.
- As a first step, its emergence might have been linked to global warming (including climatic oscillations) effects on wetlands, and its enrichment in that ecological niche was the result of C.
auris’scombined thermal tolerance and salinity tolerance.
- . Alternatively, the effect of higher UV radiation in combination with global warming might have contributed to mutagenic events that resulted in the suddenly increased fitness of a saprobe for survival in a host, via melanin- or non-melanin-dependent processes.
auris’sjump from an environmental fungus to a fungus capable of transmission to, and pathogenic for, humans might have had an intermediate host, specifically an avian host, as fungi that can grow at 40 or 42°C can infect avian fauna. Of note, sea birds may serve as reservoirs for indirect transmission of drug-resistant Candida species, such as C. glabrata, to humans.
- The uncanny ability of C
auristo adapt to specific niches, first in the environmentandthen in an avian host, might have led as a thirdstep to its ultimate establishmentasa human pathogen through genetic and epigenetic switches
The paper proposes an example of a possible pathway that C. auris followed to make it to humans:
The paper ends with a summary of the issue, that due to the thermal tolerance of fungi increasing as well as human expansion into more of the planet and global interactions, we may see the emergence of many more pathogenic fungi throughout the 21st
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. Widening of the geographic range of innately thermotolerant pathogenic fungi and the acquisition of virulence traits in thermotolerant nonpathogenic environmental fungi may shape the 21st century as an era of expanding fungal disease for both the fauna and flora of the planet.
A previous paper from 2010 by the main author from above and Monica Garcia-Solache, titled “Global Warming Will Bring New Fungal Diseases for Mammals” lays out the issue more directly, pointing to the concept that each 1 degree of warming reduces our thermal gradient by 5%:
Global warming means narrowing of the thermal gradient between ambient and mammalian temperatures. The current gradient is approximately 22°C, and consequently, every degree increase in the global average temperature reduces the gradient by about 5%. We hypothesize that with current global warming, the prevalence of fungal diseases will increase by the mechanisms previously discussed. As thermotolerance is more commonly found within the basidiomycetes, this group may be the major contributor of new fungal pathogens.
The red line in the above graph shows our body temperature, 37°C, which does not easily change except during fevers. Yet the planet is getting warmer and warmer, eroding our ~22°C thermal gradient. As compared with the time period from 20,000-6,500 years before now, from 1941 to 2009, the planet is warming more than 17 times faster! As humans, we are not going to evolve higher basal temperatures anytime soon, so as the planet warms we are going to be at more and more risk of pathogenic fungi by that closing of the thermal gradient.
Who would have thought that increasing temperatures alone would make us more susceptible to fungal infection? Prior to reading the
The risk from newly emerged fungal pathogens could be magnified by the fact that there are few antifungal drugs available and no licensed vaccines. An increased emphasis on developing vaccines with efficacy against broad fungal classes could help ameliorate new threats from the environment.
Basically, we have no real tools to fight these fungi once they evolve, so the best thing we can do right now is work to keep the temperature of the planet down to stop their further evolution. This is not my personal alarmism (although I am personally alarmed), the scientists themselves are saying it: “This information could…add urgency to ongoing efforts to slow global warming.” If every other reason wasn’t enough to slow global warming, you can now add drug-resistant pathogenic fungi to the list of top concerns.
The medical establishment does not currently have any solution to stopping Candida
The threat from C.
What can you do?
- Reach out to your elected representatives and let them know that we really are in a climate emergency and that these kinds of unknown unknowns can pose a danger to society from even slightly increased temperatures. Tell them how scared you are (or at least about how scared I am).
- Don’t vote for politicians who don’t take a strong stance on stopping climate change AND reversing it with carbon dioxide removal (CDR) techniques. We are on target to shoot past of 1.5°C carbon budget, so CDR may be our only hope at this point to slow and potentially reverse the warming of the planet, thereby stopping the further evolution
of thermallyadapted funga pathogens.
- Spread awareness of the lesser-known side-effects of climate change and why EVERY DEGREE OF WARMING MATTERS!
If you are in the medical field, please work on developing anti-fungal vaccines. If you are in the federal government or a funding agency, please provide funding for said antifungal vaccine development, as well as new anti-fungal drugs, because as of now we have no way to stop the spread of C.
As of July 12th, 2019, the CDC has identified 715 cases of C.
Paper this blog post is based on linking C.
Worldwide emergence of resistance to antifungal drugs challenges human health and food security –https://science.sciencemag.org/content/360/6390/739
Culture of Secrecy Shields Hospitals With Outbreaks of Drug-Resistant Infections https://www.nytimes.com/2019/04/08/health/candida-auris-hospitals.html
Fungal Filter On Dinosaurs to Mammals https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1002808
DNA sequencing of Candida auris https://bmcgenomics.biomedcentral.com/track/pdf/10.1186/s12864-015-1863-z
Hospital Advisory on Auris https://www.advisory.com/daily-briefing/2019/05/10/resistant-fungus