Deadly fungi are fueling the next superbug crisis. Experts say it will be even harder to beat

A new superbug threat is spreading around the world. The culprit: microscopic fungal spores that live in and on human bodies and in the dirt and air. Torrence Irvin believes the life-threatening fungi called Coccidioides entered his lungs in June 2018 while he was relaxing in his backyard in Patterson, California. “I was sitting in my lounger enjoying a nice summer day, playing games on my phone and having a cocktail,” said Irvin, who came close to death before a specialist correctly diagnosed his infection nearly a year later. “I went from a 290-pound man to 150-pound skeleton,” he said. “It came to the point where my first doctors just tossed up their hands and told my wife there’s nothing we can do. I still remember how my wife sobbed when they told her that.” Like Irvin, Rob Purdie thinks he was outside his Bakersfield, California home, working in his garden, when he inhaled Coccidioides spores in 2012. The infection soon spread to his brain, causing fungal meningitis. The condition is marked by potentially deadly inflammation of the protective membranes surrounding the brain and spinal cord. “In about 3% of people that are infected, the fungus goes somewhere else in the body, beyond the lungs to your skin, bone and joints, and other organs, or weird places like your eyeball, tooth and pinkie finger,” said Purdie, a founding member of the nonprofit MYCare, or MYcology Advocacy, Research & Education, which educates and promotes research in the field of fungal diseases. “Half the time it goes to the brain, like mine,” Purdie said. “To control my disease for the rest of my life, I have to take intracranial injections with a toxic 80-year-old drug that is slowly poisoning me.” Art imitates life — and vice versa In the HBO series “The Last of Us,” a fictional, mutant Cordyceps fungus spreads through bites from infected human hosts. (HBO and CNN share the same parent company, Warner Bros. Discovery.) In the show, the parasite quickly invades a victims’ brain, turning them into a violent, scale-covered predator with tentacles sprouting from the mouth. The real-life Cordyceps, however, only infects insects such as ants, beetles, butterflies, moths and spiders — the rest of the plot is science fiction. Reality, however, doesn’t require sci-fi zombies — fungi that maim and kill people are quickly spreading in the world today. Recent global estimates indicate there are 6.5 million invasive fungal infections and some 3.8 million deaths annually — and some of those infections are becoming more difficult to treat. Due to the emerging microbial resistance to all existing fungicidal drugs, in April the World Health Organization listed 19 fungal species as critical, high or medium priority for new drug development. Fungi in the genus Coccidioides, which infected Irvin and Purdie, are on WHO’s priority list. While deaths associated with bacterial superbugs are higher than those linked with fungi, (4.7 million vs. 3.8 million), there are hundreds of antibiotics available to treat bacteria. In contrast, only about 17 antifungal drugs are in use, according to the US Centers of Disease Control and Prevention. One reason why is the difficulty of making drugs that kill the fungus without hurting humans. “Genetically, fungi are more closely related to humans than they are to bacteria,” said infectious disease specialist Dr. Neil Clancy, an associate professor of medicine and director of the mycology program at the University of Pittsburgh. “If you’re trying to make an antifungal drug, you’ve got to come up with targets that won’t harm genes and proteins humans have,” Clancy said. “Right now, the drug we use that kills fungus best cross-reacts with human kidney cells, so you can end up with kidney failure.” Other antifungals can cause impotence, pancreatitis, liver damage and severe allergic reactions. Fungal infections in otherwise healthy people are typically resolved with current antifungal treatment, especially when caught early, specialists say. Those most vulnerable to invasive fungal infections are people with weakened immune systems, perhaps due to chemotherapy, dialysis, HIV/AIDS, immunosuppressant medications, and organ or stem cell transplants, according to the CDC. Yet neither Irvin or Purdie were immunocompromised when they contracted coccidioidomycosis, or cocci, the disease caused by the fungi they inhaled. Because researchers first identified cocci in California’s San Joaquin Valley, it’s also known as valley fever. “Some of these patients, despite not being immunosuppressed, just don’t fight off the infection well,” said fungi researcher Dr. George Thompson, a professor of medicine at the University of California, Davis, School of Medicine. “If we could figure out what’s different about their immune system, perhaps we can augment it to help them counter the fungus,” said Thompson, the specialist who diagnosed Irvin with valley fever. The most dangerous resistant fungi Cryptococcus neoformans, which causes a potentially deadly form of meningitis, topped WHO’s list of the four fungal parasites that are most critical priority for research and new drug development. The death rate from an infection with C. neoformans is extremely high, up to 61%, especially in patients with HIV infections. Aspergillus fumigatus, a mold that damages the lungs and can spread to other parts of the body, was second on the list. “Aspergillus is everywhere — your soil, in the leaves you rake, in the mulch you put down,” Thompson said. “It’s really hard to avoid and has a very high associated mortality rate —about 40% in some people — so that’s an infection for which we desperately need new drugs.” Candida auris is third on the critical list and unique in several ways. First, the microbe was already resistant to all four classes of fungicidal treatments when it first appeared in the United States in 2013. “Candida auris arrived with antifungal resistance baked in,” said Pitt’s Clancy. “It doesn’t require the emergence of new mutations in order to develop antifungal resistance.” Also known as C. auris, the yeast is unusual because it’s “sticky,” adhering to both plastic and skin in ways that other Candida species don’t, said fungal researcher Dr. Jatin Vyas, a professor of medicine at Columbia University’s Vagelos College of Physicians and Surgeons in New York City. This fungal tenaciousness makes C. auris extremely difficult to decontaminate when found in busy hospitals, nursing homes and dialysis clinics. “A patient can be colonized with C. auris, then a health care worker or someone who’s caring for them touches them and gets the organism,” Vyas said. “The caregivers can then be colonized and pass it from patient to patient.” In 2016, there were 51 clinical cases of C. auris in four states, according to the CDC. By 2023 — only seven years later — 4,514 clinical cases had been identified in 36 states. Clinical cases of the multidrug-resistant yeast rose by 95% year-over-year in 2021 alone. Candida albicans, a cousin of C. auris, is a common yeast that lives in small amounts on the skin and in the mouth, throat, intestines and vagina. C. albicans is fourth on the list of WHO’s critical priority pathogens. As part of a healthy microbiome, C. albicans lives peacefully in the body and may even play a role in boosting immunity. When that balance is disrupted by antibiotics or an immunosuppressant, however, it can cause troubling yeast infections or lead to antimicrobial-resistant invasive candidiasis. “Candida infections can end up in the bloodstream, and when they do, the mortality rates in the literature range anywhere from 40% to 60%, even with prompt diagnosis and treatment,” Vyas said. ‘High fevers alone could kill him’ Torrence Irvin began having trouble breathing in June 2018. He thought it was a cold, so he didn’t go to the doctor. The symptoms persisted, and that August, the vomiting began. “I was vomiting everything that I took in, whether it was water or solids,” Irvin said. “My wife ordered vomit bags and I would have to have one with me, no matter where I went, no matter what I was doing. I began to get weaker. I began to lose weight.” His wife of 22 years, Rhonda Smith-Irvin, was shocked at how quickly her husband deteriorated. “One time we went to the hospital twice in two days and between those days, he lost 31 pounds — I couldn’t believe it,” she said. “We were in the hospital for Thanksgiving, and he was still throwing up every day, all day.” Days in the hospital turned into weeks. With a primary diagnosis of pneumonia, Irvin said doctors couldn’t understand why he wasn’t responding to antibiotics. Being diabetic hindered his recovery. His fevers were dangerously high and hard to treat, his wife said, even with ice packed around his entire body. “He didn’t even know he was having the fevers, so I started sleeping in the hospital bed with him to alert the nurses,” she said. “They told me those high fevers alone could kill him.” As his health continued to fail, Irvin said, he was put on a ventilator — “I got to the point where I was only breathing on 20% of my lungs” — and remembers needing three blood transfusions. “It was scary for us because he was so sick, so sick,” said his mother, Brenda Irvin. “He kept saying, ‘Am I going to die?’ ‘No, you’re not going to die,’ I would tell him, ‘God is going to heal you,’” she said. “You know, I couldn’t let him go there because of my faith.” ‘It can happen to anyone’ For decades, cocci was primarily diagnosed in farmers and other outdoor workers in the arid desert and valley regions of Arizona, California, Nevada, New Mexico and Texas — places where Coccidioides microbes thrive. Today, however, cases of cocci are found in more than 20 states and have reached as far east as Pennsylvania and Maryland, according to CDC data. “The most common thought is that you only get it if you work outdoors in a dusty area. I had an indoor job. I did retirement planning,” Purdie said. Torrence Irvin also worked indoors — as a department store manager. The climate crisis, increasing wildfires and dust storms may be fueling the spread, according to research. Models of the projected spread of cocci predict a 50% rise in cases by 2100. “It can happen to anyone. Wrong place, wrong time, and they just happen to breathe in spores carried by the wind,” UC Davis’ Thompson said. “In Central California, people get this infection just driving down Interstate 5.” By the time Irvin discovered Thompson’s Sacramento clinic in March 2019, he needed a walker to travel short distances. Thompson soon put Irvin on the experimental drug olorofim as part of a phase II clinical trial to test its impact on Coccidioides. The drug is also being tested to treat Aspergillus fumigatus, the mold on WHO’s critical list. “I’d never heard of valley fever,” Irvin said. “But Dr. Thompson said we’re at the point where we’d exhausted any other option we had, so my wife and I were willing to try this.” According to Thompson, if Irvin had not had the resources to find a specialist and change his treatment, “he probably would have died from his infection.” “I worry even more for our patients with less resources who may have a really bad outcome or die because they aren’t seen by physicians who work with cocci and have access to cutting-edge treatments,” Thompson said. “We need more physicians to manage these patients, and we need to invest in the development of new drugs.” Olorofim is a daily oral medication, which means Irvin didn’t undergo invasive intravenous infusions other drugs may require during his more than three years of treatment, Thompson said. “Torrence had no side effects at all, but a few others in the trial experienced liver toxicity,” Thompson said. “But that generally could be managed by stopping the drug, restarting at a lower dose and then increasing it over time.” Today, Irvin is now off olorofim, and repeat tests show no emergence of the disease. That could change, however. “Dr. Thompson told me I would always have some form of cocci in my body based on the degree to which I had it,” Irvin said. “Still, I’ve gone from being on a walker to being on a cane, which was a huge improvement to me. It’s been a blessing. “I’m currently still out of work for the disease, but I’m stronger,” he said. “I’m back in the gymnasium working out. I’ve regained a lot of the weight back.” The damage to his lungs, however, was extensive, leaving scar tissue that Irvin says keeps him from fully recovering. “I do find myself panicking when I do get shortness of breath, wondering whether or not I need to go get looked at,” he said. “I wish I’d had listened to my body when I first got sick. If I would have responded more quickly to what I was going through, I may have been able to catch this before it went through my lungs.” That’s the message Irvin wants to send to the world — especially men like himself who, as he once did, see themselves as invincible. “We have to push our male ego aside and listen to our bodies because it will tell us when something is wrong,” Irvin said. “We need to pay attention, take care of ourselves. Health is wealth. It goes a long way.”