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From an Article by Neil Vora, New York Times, April 2, 2023
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“The Last of Us,” a postapocalyptic television thriller, recently concluded its first season with a stunning finale. However, as a physician and horror superfan, I found the show’s beginning more striking: A 1960s talk-show host asks two epidemiologists what keeps them up at night. “Fungus,” one replies.
He’s worried about a real-world species of Ophiocordyceps known to hijack the body and behavior of ants. Fast forward to the show’s central, fictional drama: a pandemic caused by a type of that fungus, which mutated as the world grew warmer. The new version infects humans and turns them into ravenous, zombielike beings whose bodies are overtaken by mushrooms.
Fungal epidemics in humans are infrequent, in part because human-to-human transmission of fungi is rare, and I am not aware of any involving zombielike creatures. It’s far more likely that the next pandemic will come from a virus. But the idea that climate change is making the emergence of new health threats more likely is solid. Could it cause a fungus ubiquitous in the environment to morph into a lethal pathogen in humans? It’s possible.
Scientists like me worry that climate change and ecosystem destruction may be creating opportunities for fungal pathogens to grow more infectious, spread over larger distances and reach more people. For example, Candida auris, a drug-resistant yeast that can be deadly in hospitalized patients, may have gained the ability to infect people thanks to warmer temperatures, according to some scientists. On March 20, the Centers for Disease Control and Prevention said Candida auris has spread at “an alarming rate” in health care facilities and is “concerning.”
But international efforts to strengthen global health security rarely consider fungal pathogens. Given that the risks are growing, that leaves us unprepared and failing to take adequate steps for their prevention. No fungal vaccines exist, diagnosis is complicated and costly, and there are not enough drugs to combat the fungus. Unless governments fund research to better address fungal disease and reverse the environmental factors that fuel their emergence, we will remain vulnerable.
For many plants and animals, fungi are a scourge. Fusarium wilt, which devastates banana plants and for which there are limited treatments, is spreading globally and is a major threat to the multibillion-dollar banana industry. An infection known as white-nose syndrome has killed millions of bats across North America. Ninety amphibian species have gone extinct from chytridiomycosis, a dreadful disease that causes a frog’s skin to fall off.
Humans have largely been exempt from fungal outbreaks because of our warm blood — 98 degrees Fahrenheit, too hot for many fungi to survive. That could be changing. A January study in the journal Proceedings of the National Academy of Sciences found that heat kicked a fungus called Cryptococcus deneoformans — which can infect humans — into evolutionary overdrive, increasing certain genetic mutations fivefold. This means more opportunities to develop dangerous adaptations, such as heat tolerance and drug resistance. In another lab study, a research team grew and heated a type of fungus known to kill insects. Within four months, two strains could reproduce at 98 degrees Fahrenheit, up from a previous limit of about 90 degrees.
Some microbiologists believe climate change is already accelerating fungal evolution in nature. Their theory is that global warming may have selected for strains of Candida auris in the environment that could survive at higher temperatures. This allowed the yeast to break a thermal barrier that previously limited spread, such that it gained the ability to infect warm-blooded birds — and humans exposed to those birds.
A changing climate may also increase the transmission of fungal disease. These microorganisms are everywhere: kitchen counters, backyard soil and the air we breathe. Typically, systemic fungal infections occur in immunocompromised individuals — cancer patients, organ recipients and others — who have inhaled spores from their environment. But regional outbreaks among healthy people are of increasing concern since flooding, cyclonic winds and wildfire smoke can create conditions for fungi to flourish and spread.
Counterintuitively, so can drought. In the American Southwest, long periods without rain have dried out the earth, leading to dust storms. Reported cases of Valley fever, a once-rare respiratory illness caused by soil-borne fungal spores, have soared nearly tenfold since 1998; the fungus has also spread to new regions, including Washington State.
A warming planet is creating more vulnerability in humans, too. Reduced crop yields, for example, lead to malnutrition, while heat stress causes kidney disease. At the same time, deforestation, inadequate safety measures on farms and commercial wildlife trade increase the risk of so-called spillovers, where viruses like Ebola jump from animals to people.
Fungi, nature’s savviest opportunists, will use these disturbances to their advantage. We saw this in the 1980s as fungal infections surged alongside H.I.V., a virus that emerged from spillover. We also saw it more recently when a unique fungal disease affected thousands of people in India who had received immune-suppressing steroids as part of their treatment for Covid-19.
Last October, the World Health Organization created a list of “fungal priority pathogens” for the first time. “Fungal pathogens are a major threat to public health,” the group wrote. This was an important symbolic gesture, but it does not give doctors what they need: better tools to fight these infections. There are no approved vaccines. Globally, many countries lack the capacity to diagnose certain common fungal diseases. Even in New York City, where I treat patients, it can take weeks for some to receive a diagnosis for fungal infections. Worse yet, many fungal pathogens already are resistant to the few antifungal drugs we do have available.
In part, this is a technical challenge: It’s difficult to develop antifungals that don’t also destroy our cells. But we cannot develop cures if we don’t try — and right now, fungal research output is abysmal. For example, cryptococcal meningitis, a fungal infection, kills more people than bacterial meningitis caused by Neisseria meningitidis, yet the latter receives over three times as much research funding.
Fungal pathogens simply haven’t been on government funders’ radar — they receive just 1.5 percent of all research funding for infectious disease research. Likewise, pharmaceutical companies have little incentive to invest in research and development, because the potential profit is limited.
To help fill this void, the National Institutes of Health must increase support for the study of fungal diseases, as it recently did for Valley fever. The U.S. Biomedical Advanced Research and Development Authority, which helps develop vaccines and drugs for public health emergencies through public-private partnership, must also make them a priority. Currently, none of the 83 initiatives listed on the B.A.R.D.A. medical countermeasures portfolio website are for fungal pathogens, though it has announced its support for the development of novel antifungals.
This moment also calls for humility. In the 1960s, some prominent experts erroneously believed infectious diseases were a diminishing threat. But nature is full of surprises.
From 2012 to 2021, I investigated outbreaks with the Centers for Disease Control and Prevention. As my colleagues and I responded to Ebola, rabies, poxviruses and coronaviruses, we saw firsthand how the ways people interact with the environment and animals can surface disease in horrific and unexpected ways. Often, we don’t learn how devastating these diseases are until we are in the midst of a full-blown emergency. With only 5 percent of an estimated 1.5 million fungal species identified to date, fungi are perhaps the great blind spot in public health.
Our health depends on a delicate ecological equilibrium. Maintaining that balance — by weaning ourselves off of fossil fuels to slow climate change and halting the loss of nature to prevent viral spillovers — is perhaps our best hope for avoiding a fungal horror show.
>>> Dr. Neil Vora is the pandemic prevention fellow at Conservation International and led New York City’s Covid-19 contact tracing program from 2020 to 2021.