Deadly fungal infection may have emerged due to global warming, cases reported from over 30 countries

The researchers suggest this is the beginning of fungi adapting to higher temperatures, and call for better surveillance systems


                            Deadly fungal infection may have emerged due to global warming, cases reported from over 30 countries

A life-threatening, multi-drug resistant fungal infection is the first example of a new fungal disease that has emerged owing to climate change, according to researchers. The fungus, called Candida auris (C. auris) was first isolated in 2009 from a human ear (thus named auris), and since then it has been associated with human disease in many countries.

Now, researchers have concluded that global warming may have played a significant role in the emergence of C. auris, which is often multi-drug resistant and is a serious public health threat. The research was conducted by scientists at Johns Hopkins Bloomberg School of Public Health, Baltimore; the University of Texas-MD Anderson Cancer Center, Houston; and Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands. 

According to their reasearch, the fungus has adapted to higher temperatures, and as they adapt, they are likely to "break through human’s protective temperatures.”

“To our knowledge, this would be the first microbe where virulence is proposed to arise by adaptation to higher temperatures such that it can then grow in human tissues. The argument that we are making based on comparison to other close relative fungi is that as 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,” Dr. Arturo Casadevall, Chair, Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore (Maryland) told MEA Worldwide (MEAWW).

He adds, “For those who contract C. auris infection, it is very dangerous since it is difficult to treat and has a high mortality. It is more dangerous for people who already have a weakened or compromised immune system.”

What is extremely concerning, say the researchers, is that global warming may lead to new fungal diseases that are not known currently. According to the research team, the findings suggest that this is the beginning of fungi adapting to higher temperatures, and there will be more problems in the future.

“There is a concern that this could occur with other fungi with pathogenic potential such that humanity can face new fungal threats in the future. Global warming will lead to the selection of fungal lineages that are more thermally tolerant, such that they can breach the mammalian thermal restriction zone,” he told MEAWW.

Their findings have been published in mBio, an open-access journal of the American Society for Microbiology.

A serious global health threat

According to the Centers for Disease Control and Prevention (CDC), it is a type of yeast which has been causing severe illness in hospitalized patients in several countries, and the disease can be fatal. So far, C. auris infections have been reported from over 30 countries, including the US. In the US, as of May 31, 2019, 685 confirmed cases had been reported, and  most C. auris cases have been detected in the New York City area, New Jersey, and the Chicago area. 

“Based on information from a limited number of patients, 30–60% of people with C. auris infections have died. However, many of these people had other serious illnesses that also increased their risk of death," says CDC. 

The CDC says in some patients, this yeast can enter the bloodstream and spread throughout the body, causing severe ‘invasive’ infections. It often does not respond to commonly used antifungal drugs, making infections difficult to treat. Most strains detected so far have been resistant to at least one drug; more than one-third are resistant to two drug classes, and some strains are resistant to all three drug classes used to treat fungal infections.

“Patients can remain colonized with C. auris for a long time, and C. auris can persist on surfaces in healthcare environments. This can result in the spread of C. auris between patients in healthcare facilities. C. auris has caused bloodstream infections, wound infections, and ear infections,” says the CDC. 

Capable of growing at higher temperatures than most of its closely related species

The most enigmatic aspect of its rise as a human pathogen is that Candida auris emerged independently on three continents simultaneously - India, South Africa, and South America - and the isolates were not related. Until now, the mechanism(s) responsible for the simultaneous emergence of three different clades of C. auris in three geographically distant regions had remained a mystery. 

“The isolates from these regions are genetically different, so they represent different strains of the microbe. Something happened to allow this organism to bubble up and cause disease. Hence, we began to consider global changes that would affect such diverse regions, and climate change seemed the potential culprit,” explains Dr. Casadevall.

Proposed scheme for the emergence of C. auris, according to the study. (mBio)

 

Fungal infections are usually rare in humans as they cannot tolerate human body temperature. “The reasons that fungal infections are so rare in humans is that most of the fungi in the environment cannot grow at the temperatures of our body. Mammalian resistance to invasive fungal diseases results results from a combination of high basal temperatures that create a thermal restriction zone and advanced host defense mechanisms in the form of adaptive and innate immunity,” says the study.

Accordingly, the researchers compared the “thermal susceptibility” of C. auris to some of its close relatives and found that the majority of the relatives could not tolerate or survive the temperatures resembling a human body. In contrast, the researchers found that C. auris is capable of growing at higher temperatures than most of its closely related species. Accordingly, say the researchers, adaption to higher temperatures is one contributing cause for the emergence of C. auris. They add as they adapt, they can break through the protective barrier or the thermal restriction zone of humans. 

“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 a 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,” says the study.

It adds, “Thus far, the majority of human cases of C. auris-related disease have occurred in debilitated individuals, such as those in intensive care units. Because their debilitated conditions impair their immunity, this group may serve as sentinels for the appearance of new fungal diseases.”

According to the researchers, the greatest lesson from the emergence of C. auris is the need for greater vigilance and continuous monitoring. “In this regard, the environment is likely to contain large numbers of fungal species with pathogenic potential that are currently non-pathogenic for humans because they cannot grow at mammalian temperatures. 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 findings recommend. 

Dr. Casadevall says that if better surveillance systems were in place, the rise of C. auris would have been detected earlier. He recommends the need to invest in better surveillance of fungal diseases.

“We are pretty good at surveilling influenza and diseases that cause diarrhea or are contagious, but fungal diseases are not usually contagious, and therefore nobody has bothered to document them well. If more fungi were to cross over, you really would not know until somebody started reporting them,” he says.

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