The hospital was doing everything it could. It set up a separate unit to house COVID-19 patients. It imposed exhaustive hygiene measures to keep the virus from spreading. It even used ultraviolet light for sanitization, which at that time – July 2020 – was being marketed with great enthusiasm as a way to zap COVID particles out of thin air.
Still, patients at this Florida medical unit remained gravely ill. Ventilators, feeding tubes, catheters pumping medicines straight into patients’ hearts – none of it seemed to be enough.
The battle against the virus raged on.
That’s when a blood test came back with a peculiar result. Then another. Then another.
COVID, it turned out, wasn’t the only enemy. The patients were positive for a fungus: Candida auris, or C. auris for short. This wasn’t just any old yeast. C. auris—a “superfungus” associated with that scientists think may be linked climate change— is capable of can cause invasive, sometimes life-threatening infections, according to the CDC. Florida’s first reported case was in 2017, and since then, the organism has cropped up across the state. In the COVID unit that was set up in the summer of 2020, about some 35 patients tested positive for the fungus in just 2 weeks. Within 30 days, eight had died.
Today, the threat of superfungi is still on the rise, and it’s hardly limited to the Sunshine State. As heat and drought ravage many parts of the country, drug-resistant fungi are spreading. Floods cause the deadly strains to mingle with more benign ones, enabling antimicrobial-resistant genes to jump between species. Hurricanes are pulling entombed fungi from beneath the earth, showering the air with potentially deadly mold.
Meanwhile, the arsenal against superfungi is sparser than ever, as decades-old medicines aren’t as effective and new drug legislation is stalled in Congress. “We’re sort of where we were 30 years ago,” says John Rex, MD, chief medical officer at the drug company F2G and a former member of the FDA ’s Anti-Infective Drugs Advisory Committee. “There remain very few options.”
By the standards of nature, C. auris is a baby. It was first identified at the Teikyo University Institute of Medical Mycology, after doctors in a Tokyo hospital had a hard time treating a 70-year-old woman whose symptoms suggested a basic ear infection. What researchers found was anything but basic: small, pill-shaped cells that indicated a distinct species. Their case study was published in 2009, but C. auris wasn’t discovered in the United States until 2016.
A baby, perhaps, but far from harmless. Almost 20% of patients in the first series of U.S. cases died within 30 days of getting the fungus. The number doubled within 3 months.
It’s essential not to confuse C. auris with its less virulent cousins like C. albicans, which is easily treatable, notes Tina Tan, MD, an infectious disease specialist at Lurie Children’s Hospital and vice president of the Infectious Diseases Society of America. “You really have to be vigilant,” Tan says, “and understand what you’re dealing with.”
Now C. auris is at the top of the CDC’s most-wanted list. Earlier this year, the agency called the fungus an “urgent” threat “because it is often resistant to multiple antifungal drugs, spreads easily in healthcare facilities, and can cause severe infections with high death rates.” A paper based on CDC data noted a “dramatic increase” in the spread of the fungus, with 17 states reporting their first-ever cases between 2019 and 2021. Since then, 18 more states have seen first cases of their own.
The outbreaks “demonstrate how easily something can spread,” says Meghan Lyman, MD, medical officer in the CDC’s Mycotic Diseases Branch.
C. auris is distinctive in ways that make controlling outbreaks a tall task, she says. The fungus is hardy: It can survive for weeks on surfaces ranging from toilets to telephones. It’s tenacious: Products like Purell, Lysol, and Virex may not keep it from spreading. It’s evasive: Traditional biochemical tests often misdiagnose it or fail to detect it at all. And it’s a shape-shifter, appearing sometimes as lines, other times as ovals; sometimes in isolation, other times in clusters.
Given how easily it spreads, health professionals face a tough challenge. Jeffrey Rybak, PharmD, PhD, a pharmacist and antifungal resistance researcher at St. Jude Children’s Research Hospital, has received calls from a colleague across the country seeking advice on how to quell the outbreak. “You have to have concern for the patient in front of you–and equal concern for the other patients in the facility,” he says. Often, Rybak says, “you’re fighting a losing battle from the infectious control standpoint.”
C. auris didn’t come out of nowhere. Researchers say it’s here because of climate change, which makes it one of the first infectious diseases–some say thefirst–directly linked to the climate crisis.
A group from Johns Hopkins, MD Anderson Cancer Center, and the Netherlands cites several reasons: warmer environments that are about the same temperature as the human body, droughts that lead to saltier wetlands akin to the bloodstream, and intense ultraviolet light exposure that fosters mutations. Although the authors concede that global warming is “unlikely to explain the whole story,” they say the emergence of C. auris “stokes worries that humanity may face new diseases from fungal adaptation to hotter climates.”
It’s telling that states severely affected by climate change report the most cases of C. auris. Nevada, for example, has had prolonged heat waves in recent years, as well as an intense drought that threatens the Colorado River Basin, according to the National Oceanic and Atmospheric Administration. Not coincidentally, the state has seen an extraordinary number of C. auris patients relative to its population–more than 1,600, according to the Nevada Department of Health and Human Services. As of July 2023, about 140 of them had died.
Mark Pandori, PhD, director of the Nevada State Public Health Laboratory, has been tracking the outbreaks since the beginning. He notes that there are only three types of antifungal drugs, and since superfungi may be resistant to one or more of them, treatment alternatives are limited. Adding to the problem, these options are often toxic. One of the drugs is amphotericin, which can cause reversible kidney injury.
Given how hard it is to identify C. auris in the first place, cases have likely been underreported, according to Pandori. With uncertain data, doctors don’t always know when and how to intervene. “It’s like any other challenge, military or otherwise,” he says. “You don’t have information, you can’t act.”
Of course, C. auris isn’t the only medical challenge linked to global warming. Consider, for example, the 2010 case of a boy in Washington state who went to the pediatrician complaining of chest pain. At first, doctors didn’t see a need to hospitalize him, but that changed when, within 3 days, he began to have trouble breathing. Tests later showed that his lungs contained coccidioides, the bug that causes valley fever, a fungus usually found about 1,000 miles to the south. It was Washington’s first documented case. A case report notes “climate changes conducive to colonization, allowing expansion into new regions.”
In other words, climate change isn’t just giving rise to new superfungi; it’s also allowing old fungi to flourish. “Small temperature changes for fungi cause them to adapt, or go away, and for other organisms to move in,” says Tom Chiller, MD, chief of the CDC’s Mycotic Diseases Branch.
Since coccidioides first appeared in Washington, fungi once limited to certain regions have been found far from their original homes. Valley fever is more common well outside the Southwest valleys for which it is named. Histoplasmosis, triggered by a fungus usually found in Ohio, is now in Michigan and Minnesota. Blastomycosis, normally linked to caves in the Southeast, has turned up in states as far-flung as Texas and Vermont.
For most people, common fungal infections– thrush, athlete’s foot, diaper rash– are easily treatable with wipes, drops, or ointments. These conditions can be more serious for more vulnerable patients like newborns, the elderly, and the estimated 9 million Americans with compromised immune systems.
And as old fungi spread to new regions, some become more deadly. Case in point: Aspergillus fumigatus. Hospitalizations from this ubiquitous mold have jumped 40% in recent years. It now tops the CDC’s Watch List of resistant organisms that can “spread across borders and cause significant morbidity and mortality,” but whose “full burden … is not yet understood.”
That has been Tan’s experience in Chicago, too. In the past decade, she’s seen more severe cases of blastomycosis. Where once kids came in just with lung disease, they now have fungal abscesses in their bones and skin. In hotter, more humid conditions, Tan says, fungi tend to be “driven into overdrive.”
To curb the spread and combat antimicrobial resistance, policymakers and industry leaders worldwide have stepped up.
On the one hand, they’re naming the issue. In 2013, U.S. Rep. Kevin McCarthy, R-CA, founded the Valley Fever Task Force, which set out to help develop new antifungal medicines through the FDA. But progress has been sluggish. Almost a decade after the task force was established, McCarthy continued to emphasize “the critical need to find effective treatments.”
On the other hand, they’re proposing legislation. In 2021, McCarthy introduced the Finding Orphan-disease Remedies With Antifungal Research and Development (FORWARD) Act, with the hope that the National Institutes of Health would target coccidioidomycosis, among other fungal infections, and the FDA would make development of antifungal drugs a priority. But the FORWARD Act remained stuck in the House. In 2022, Rep. Anna Eshoo, D-CA, reintroduced a pared-down version as part of a larger law. That bill, with further refinements, was passed in the House in June 2022 and adopted by Congress in December 2022.
Don’t count on a breakthrough right away. The bill gave the FDA almost 5 years to enact guidance that would lead to new drugs. No such guidance had been issued as of August 2023, according to Beth Fritsch, an FDA external affairs officer.
Money is being poured into drug development. For example, there’s the Antimicrobial Resistance (AMR) Action Fund, a joint investment involving the International Federation of Pharmaceutical Manufacturers and Associations, the World Health Organization, the European Investment Bank, and Wellcome Trust. But antifungals aren’t a top priority. The fund hasn’t yet targeted yeast like C. auris or molds like aspergillus.
Without that support, developing antifungals will be held back, according to Rex at F2G. The relative rarity of cases tends to make clinical trials complicated and expensive, and with the path to faster FDA review stalled in Congress, the approval process can take years. For drugmakers, the financial incentive is less than compelling, Rex says, noting that they “are still more interested in cancer or Alzheimer’s.”
Options keep growing slimmer as superfungi swarm. Rex likens the problem to infrastructure maintenance: Tending to sewage lines rarely tops anyone’s list of priorities– until there’s a catastrophe. “It’s important to take care of your pipes, but it’s not fun,” he says. “Paying for preparedness is not fun.”
To raise awareness, the CDC’s Lyman is hitting the road, educating as many doctors as she can and calling for a sense of urgency. “There are a lot of places where it just doesn’t seem to be a problem for them,” Lyman says.
“Until it’s a problem for them,” she adds.
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2023-09-14 00:46:06
