Deadly fungi erupting in hospitals, will climate change make The Last of Us a reality?

Lorraine, 86, died last summer after contracting Candida auris. Doctors believe Rowling likely contracted the fungus from an oxygen tube at the hospital, and Candida auris caused her to develop sepsis and kidney failure, which eventually led to a stroke that took her life.

On March 20, 2023, the U.S. Centers for Disease Control and Prevention (CDC) declared that Candida auris has become an urgent public health threat. Since it first appeared in the U.S. in 2016, the fungus has been detected in more than half of U.S. states, especially in the past few years, with a sharp rise in detected cases. It can spread from person to person and is increasingly resistant.

The rapid spread of Candida auris is a bizarre echo of the fictional apocalypse of a recent hit American drama, "The Last of Us": In the show, a real, ant-parasitic fungus "Ophiocordyceps" mutates with global warming and begins to infect humans and create zombies.

A still from "The Last of Us"

In the real world, as early as 2019, a study by Professor Arturo Casadevall, a microbiologist at Johns Hopkins University in the United States, pointed out that climate change is accelerating the evolution of fungi in nature, and global warming may cause Candida auris to be more adapted to human temperature.

Fungal infections cause about 1.7 million deaths worldwide each year, and more than 150 million people are severely infected. But previously, fungal diseases had been neglected for a long time, and human-to-human transmission was uncommon. However, things now seem to have changed. How should we deal with Candida auris? Will its outburst slide our world toward the fungal apocalypse of The Last of the Survivors? Will climate change cause ubiquitous fungi in the environment to become deadly pathogens? The Paper (www.thepaper.cn) interviewed a number of American experts in fungal research and clinical medicine to try to answer these important questions.

Experts interpret the difficulties of prevention and control

In recent years, the number of cases of Candida auris infections confirmed by testing has risen rapidly in the United States.

According to the U.S. Centers for Disease Control and Prevention, from 2019 to 2020, the number of people infected with Candida auris in the United States increased by 59% to 756. In 2021, it doubled again to 1,471. Compared to 2019, the incidence increased by 21% in people who were not infected with the fungus but colonized by it, and by 209% in 2021. (Colonization is when the fungus attaches to parts of the body and can multiply without causing infection.) )

One of the biggest challenges in dealing with Candida auris is that it can lie dormant on contaminated surfaces for weeks, colonizing the human body and in the medical environment for a long time. Scott Roberts, deputy director of infection prevention at Yale School of Medicine, told The Paper: "Once a person is colonized by Candida auris, or a facility that houses patients infected with Candida auris, the fungus is difficult to eradicate and it is resistant to common disinfectants." ”

Candida auricularis

William Schaffner, a professor of preventive medicine in the Department of Health Policy at Vanderbilt University School of Medicine, told The Paper that only strict prevention and control measures can reduce the spread of Candida auris in hospitals, "Patients must be isolated, medical isolation gowns, gloves and masks must be worn to treat patients; All kinds of surfaces in the hospital must be strongly disinfected, and they must be done very thoroughly every time. ”

Once Candida auris breaks through the prevention and control of the hospital, it can have a fatal impact on the patient. According to the CDC, nearly half of patients infected with Candida auris die within 90 days.

"Candida auris preys on people who are already ill and hospitalized, are receiving medical care and using antibiotics. It can lead to deaths from already having serious illnesses, with mortality rates ranging from about 15 percent to 30 percent or even higher. Professor Schaffner told The Paper. The infection mechanism of this fungus can either cause an aggravation of an already sick person or directly cause a very serious disease.

Fortunately, Candida auris has little effect on healthy people. "Ordinary healthy people don't need to worry about this, Candida auris is not very threatening in this sense." Schaffner said.

However, clinical diagnosis remains inadequate. According to the US Centers for Disease Control and Prevention, it is difficult to identify Candida auris through standard laboratory methods, and it is easy to be misidentified in laboratories without specific technology. Several experts said hospitals had difficulty identifying Candida auris infections at an early stage and needed training to improve laboratory diagnosis. This means that by the time Candida auris was first diagnosed, it may have spread quite widely.

Even if hospitals are capable of making the correct diagnosis, treating Candida auris infections is a major challenge because the fungus is drug-resistant. Meghan Lyman, a medical worker in the Department of Mycology at the CDC, told The Paper that there are currently only three main classes of antifungal drugs available to treat Candida auris infections, and more and more cases are resistant to all three classes of drugs.

In addition to medications, can vaccines help us deal with Candida auris? "Unfortunately, we don't yet have any vaccine against fungal diseases. Only three have reached human trials, and they have not yet been put on the market. Robles said.

Several new antifungal drugs are under development and have the potential to be used to treat Candida auris.

Climate change may make fungi more adaptable to the human body

Candida auris was first detected in the ear of an elderly patient in Japan in 2009. Since then, cases of infection have been detected in different parts of South Africa, South America and North America.

What is the reason for the outbreak of Candida auris infections in recent years? One important reason, Robles believes, may be that climate change is leading to the growth of fungal pathogens.

"Candida auris was not detected until 2009 and emerged independently on 4 continents, where it can survive at higher temperatures compared to other fungi. This all supports the hypothesis that climate change is an important cause of the emergence of Candida auris. He told The Paper.

This hypothesis is supported by relevant research papers. A 2019 study by Professor Arturo Casadevall, a microbiologist at Johns Hopkins University, said that higher ambient temperatures lead to the selection of fungal lineages becoming more heat-resistant. That is to say, under the condition of rising global temperature, fungi will tend to produce isolated strains that are more suitable for human temperature than the previous generation of strains, and then evolve heat tolerance, so that Candida auris can break the temperature barrier that previously limited its spread, so as to obtain the ability to infect warm-blooded birds and humans who come into contact with birds.

However, while climate change may have played an important role in the emergence of Candida auris, this variable is unlikely to explain the entire evolutionary process. For example, it is difficult to see how global warming alone explains the spontaneous emergence of the four clades of Candida auris strains in geographically different regions, unless there is another common epidemiological variable that facilitates interactions with humans that make the virulence of Candida auris apparent.

Meghan Lyman, a medical staff member in the CDC's mycology department, said it was unclear whether or how climate change contributed to the emergence of Candida auris because "most cases are the result of transmission in a healthcare setting."

However, more research supports the link between global warming and fungal evolution. A study published in January in the journal Proceedings of the National Academy of Sciences (PNAS) found that high temperatures put Cryptococcus deneoformans, a fungus that can infect humans, into evolutionary overdrive, increasing certain genetic mutations fivefold and making it easier to develop heat tolerance and drug resistance.

In another laboratory study, a team of researchers cultured and heated a fungus known to kill insects. Within four months, two strains could propagate at temperatures of 36.7 degrees Celsius, up from the previous limit of about 32.2 degrees Celsius.

Previously, humans largely did not have to worry about fungal outbreaks because fungi needed to grow at temperatures lower than human body temperatures. But with climate change, this is gradually changing.

"As the climate continues to warm, we will continue to face new and emerging fungal threats, and I am very worried about the future." Robles said.

How far are we from The Last of the Survivors?

Is it possible for a human-to-human transmission fungus like Candida auris to cause outbreaks in healthcare facilities worldwide?

Professor Schaffner expressed concern about cross-country transmission: "How do fungi spread from country to country? One possible avenue is medical tourism, where people travel from one country to another to receive medical care, and they may have contracted a fungus in a foreign country, then returned home and spread the fungus. ”

In fact, reality has confirmed Professor Schaffner's fears. A recent study published in the Journal of Clinical Medicine reports that a growing number of countries have reported similar cases: increasing cases of Candida auris in northern Italy. Previously, a strain of Candida auris infected at least 451 patients in South Africa between 2012 and 2016. Back in 2019. The Beijing Municipal Center for Disease Control and Prevention has also released news that a small number of cases have also appeared in China. Currently, India and Pakistan have the highest number of cases in the world.

On January 23, 2018, local time, in the laboratory of the University of Würzburg, Germany, researchers held a Petri dish containing Candida auris.

Although Candida auris is currently not a threat to healthy people, can a person who carries the fungus but does not get sick transmit it to others? "We don't think it's common," Dr. Schaffner said, "but it needs more research." ”

While there is no need to be overly concerned, the outbreak of Candida auris in U.S. healthcare facilities is a wake-up call for the public and public health agencies: medical institutions need to step up efforts to prevent Candida auris from infecting vulnerable populations such as patients; Are there any other fungi that could spread similarly in the future? Could they have evolved to be more adapted to the human body? Is it possible that the crisis depicted in "The Last of Us" is possible?

In 2022, the World Health Organization (WHO) listed 19 fungal "priority pathogens" that pose a threat to public health, with Candida auris among the most important key priority groups, along with Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans.

Experts see the list as a concrete action by the World Health Organization to shift its focus to fungal infections. Until humanity ushers in a "fungal crisis," we still have room to act.