Once-rare fungal diseases are killing millions in an unprepared world

Japan Times

02-04-2025

When most people think of dangerous infections, they picture bacteria or viruses. But for infectious disease specialists like Peter Chin-Hong, one of the most insidious threats lurking in hospitals and clinics today is fungal.
Chin-Hong's case list is long: a healthy 29-year-old marathon runner from California's Central Valley whose heart lining was invaded by Coccidioides, a soil-dwelling fungus; a lung transplant recipient coughing up mold nodules — fungal growths scattered throughout his lungs — after stopping antifungal medication; and a 45-year-old woman with poorly controlled diabetes, infected by a black fungus that destroyed part of her face and spread to her brain. Despite multiple surgeries and treatment, she died in the hospital.
"These aren't rare anymore,' said Chin-Hong, associate dean and professor of medicine at the University of California, San Francisco. "We're seeing them every day.'
Once considered obscure or opportunistic, invasive fungal infections are now surfacing with alarming frequency — and in patients and places doctors never used to worry about. Climate change is expanding the geographic reach of fungi. Medical advances like organ transplants, chemotherapy, and intensive care are saving lives, but they also leave more patients immunocompromised. Even common conditions like diabetes raise the risk of severe fungal disease.
An estimated 6.5 million people develop invasive fungal infections each year, with about 2.5 million deaths directly caused by them — roughly twice the global toll of tuberculosis.
Many of those deaths are in people with advanced HIV, and experts warn the problem may worsen as funding for global HIV/AIDS programs is pulled back. A surge in AIDS-related illness, they say, could turbocharge the fungal crisis, especially in low-resource settings where diagnostic tools and antifungal treatments are already limited.
Adding to the danger is the rise of drug-resistant infections — strains that no longer respond to the limited arsenal of antifungal medications. Candida auris, a newly emerging yeast first seen in 2009, has already triggered deadly outbreaks in hospitals and long-term care facilities. Experts warn that broader resistance could soon outpace the slow development of new drugs.
Fungal crisis
The World Health Organization warned Tuesday of critical global gaps in the ability to diagnose and treat fungal infections. That includes the dangerously thin pipeline of medicines, with just four new antifungals approved globally over the past decade. Of the nine currently in clinical development, only three have reached the final stage of patient studies.
"We can expect few new approvals in the next 10 years,' said Valeria Gigante, who leads the antimicrobial resistance division at WHO in Geneva.
More than half of the antifungal candidates in development lack true innovation, limiting their ability to counter emerging resistance, Gigante added. "We always need new ways to kill dangerous fungi,' she said. "Only three of the nine candidates even target the most critical pathogens.'
Fungal threats have remained dangerously overlooked, said Justin Beardsley, an infectious diseases doctor and University of Sydney researcher who contributed to both WHO reports. "Fungus is not on anybody's radar,' he said. "It's unobserved and out of control — which means we're not developing mitigations.'
He also pointed to growing concern over agricultural antifungal use.
"A lot of the new drugs being developed don't have a novel mechanism of action,' Beardsley said. And in many cases, new compounds are introduced faster in agriculture to protect crops from diseases like powdery mildew. "That is just really disheartening for human drug developers — and a little bit worrying for public health, that our new-hope drugs are already going to be getting exposed to a biosimilar agent in the environment and we're going to get resistance.'
Another shortcoming is around diagnostics, with the WHO cautioning that even when tests exist to identify deadly fungi, they're often unavailable in low— and middle-income countries. Most rely on well-equipped laboratories and trained personnel. The development of systems to detect invasive fungal infections and determine drug susceptibility is also lagging behind what exists for bacteria, Gigante said.
Unseen foe
Fungal infections behave differently from bacteria and viruses. They rarely spread person to person. Instead, most come from the environment — moldy soil, decaying plants, airborne spores. Some spores can even travel high into the atmosphere and drift across continents, making them especially hard to track or control.
That makes it nearly impossible to fully protect vulnerable patients. UCSF's Chin-Hong said doctors often prescribe preventive antifungal medication to people at high risk, such as those who've had lung or blood stem cell transplants. But the drugs don't cover every type of mold. Mucormycosis — a rare but aggressive infection — is notoriously difficult to treat.
"Mucormycosis is probably the scariest one we have,' Chin-Hong said. "If it gets into the lungs, the death rate can be as high as 87%.' The fungus can also invade the sinuses and spread to the brain, with a mortality rate around 50%. It causes tissue to die — cutting off blood flow so antifungal drugs can't reach the infection site.
"You have to surgically remove the infected area,' he said. "A lot of times people have their eye taken out because it goes up through the sinus cavity, and there's no good treatment for that.'
Resection — surgically removing infected tissue — is sometimes possible in the sinuses or skin. But in the lungs, it's often far more difficult. "The reason lung mortality is so high is because you can't just cut out big chunks of lung,' Chin-Hong said.
And even when drugs work, they're often less effective in the very patients who need them most — those with weakened immune systems.
"We have agents now,' Chin-Hong said, "but we're running out of them.'