http://www.wsj.com/articles/deadly-fungi-are-infecting-more-americans-11666568576?

Deadly Fungi Are Infecting More Americans

Drugmakers pursue stronger, less toxic treatments as fungal infections rise

Candida auris fungi, pictured in a petri dish, appear to have adapted to warmer temperatures, making them better suited to surviving inside humans. PICTURE ALLIANCE VIA GETTY IMAGES

By Dominique Mosbergen, Oct. 24, 2022 5:30 am ET

It wasn’t the cancer or rounds of chemotherapy and radiation that almost killed David Erwin. It was a fungus most people inhale every day. 

Fungal infections kill more than 1.6 million people yearly, according to Global Action for Fungal Infections, a research and fundraising organization. The toll is climbing. Fungi are adapting to rising temperatures in ways that may make them better suited to thrive in the human body, researchers said. And more people undergoing treatments that weaken their immune systems means a larger population vulnerable to severe fungal infections. 

At least 7,000 people died in the U.S. from fungal infections in 2021, the Centers for Disease Control and Prevention said. In 1969, the CDC reported 450 such deaths. Current cases are likely undercounted because of misdiagnoses, the agency said.

“Public awareness of fungal infections is abysmal,” said Peter Pappas,  an infectious-disease specialist at the University of Alabama at Birmingham. “They think of toenail fungus or jock itch. They don’t understand that with some of these invasive fungal infections, if left untreated or even when they are treated, they can often lead to death.” 

Mr. Erwin, a 60-year-old former manager at a trucking company, hadn’t heard of the fungus Aspergillus until the spring of 2021, when a neurosurgeon dug out a colony of it from his brain. 

David Erwin hadn’t heard of the fungus Aspergillus until last year, when a neurosurgeon dug out a colony of it from his brain. PHOTO: DAVID ERWIN

Mr. Erwin, who lives in Joliet, Ill., had completed chemotherapy for throat cancer in 2020. He said he continued to experience symptoms that flummoxed physicians. He lost the use of his right arm and leg and developed back pain so debilitating that for months he said he could barely move without screaming. The mass the surgeon removed helped confirm that Aspergillus had colonized his brain, lungs and spine. The common mold can grow on carpets, pillows and in air conditioners. 

“Aspergillus is everywhere,” Mr. Erwin said. “It could be in your backyard.”

More than 75,000 people are hospitalized in the U.S. every year with fungal infections, one-fifth of which are caused by Aspergillus, the CDC said. Fatality rates associated with some fungal infections including severe cases involving Aspergillus can exceed 50%, research shows.

Fungi, which were among the first complex life-forms on land, became a global public-health threat about 35 years ago amid the HIV/AIDS epidemic as immunocompromised populations began to increase globally, said Michail Lionakis, head of fungal pathogenesis research at the National Institute of Allergy and Infectious Diseases.

Immunocompromised people, including those taking medications that suppress the immune system, are at particular risk of severe fungal infections, infectious-disease experts said. At least seven million people in the U.S. are immunocompromised, according to the CDC, and Dr. Lionakis said the population is growing as more people receive treatments like chemotherapy and organ transplantation.

The CDC last month urged patients and healthcare providers to consider fungi a potential culprit if an infection isn’t responding to treatments. The World Health Organization said it plans this year to release a list of priority fungal diseases that it hopes will spur funding for research and drug development.

The Food and Drug Administration has approved four classes of antifungal medications for invasive infections. A new class to treat severe diseases hasn’t been approved in over two decades. Most antifungals for serious infections are toxic, some even at low doses. There are no approved vaccines targeting fungi. 

Several antifungal drugs are in development and researchers are probing potential vaccines. In a Phase 2 trial, Amplyx Pharmaceuticals Inc.’s antifungal fosmanogepix was found to be effective against Aspergillus, a yeast known as Candida and other rare molds and was well-tolerated by patients. Pfizer Inc. acquired Amplyx last year.

Cidara Therapeutics Inc. said it has submitted its drug rezafungin, which was shown in trials to eradicate Aspergillus and Candida, for FDA approval. Matinas BioPharma Holdings Inc. said it is developing a nontoxic and oral version of amphotericin B, one of the oldest and most potent—but also most toxic—antifungals. F2G Ltd. said Friday that the Phase 2 clinical trial for its antifungal olorofim, developed to treat patients with severe infections caused by Aspergillus and other rare molds, had found the drug to be effective in almost half of patients for whom current therapies didn’t work and was mostly well-tolerated.

Drug companies are developing treatments for fungi including Aspergillus, left, and Candida auris, as seen through microscopes.BSIP/EDUCATION IMAGES/UNIVERSAL IMAGES GROUP/GETTY IMAGES

Unlike bacteria and viruses, fungi, like humans, have eukaryotic cells with complex structures and a clearly defined nuclei—a biological similarity that makes developing nontoxic antifungals and vaccines challenging, researchers said. “It’s hard to make antifungals that are not anti-human,” said Andrej Spec, an associate professor of medicine at Washington University School of Medicine in St. Louis.

Rising temperatures may be propelling the spread of some dangerous fungi by encouraging them to adapt in ways that help them better infect humans, said Dr. Spec, who runs a clinic focused on invasive fungal infections. His research shows that potentially deadly fungi including Blastomyces and Histoplasma have significantly expanded their range in the U.S. since the 1950s to include most U.S. states. 

Pathogens need to withstand the human body’s average temperature of 37 degrees Celsius, which is too hot for most fungi to thrive, said Felipe Santiago-Tirado, a fungal-infection expert at the University of Notre Dame. But some fungi, including the deadly species Candida auris, appear to have adapted to warmer temperatures, making them better suited to surviving inside humans, he said. The first known Candida auris infection was reported in Japan in 2009. Candida auris infections have since been reported in about half of all U.S. states.

“Body temperature used to be a big barrier,” said Dr. Santiago-Tirado. “But now Candida auris is a big problem.

The overuse of antibiotics is also contributing to the burgeoning threat of fungal infections, infectious-disease experts said. When antibiotics kill bacteria in the body, including types that support the immune system, aid digestion and fight pathogens, they create a void that fungi can exploit. 

Amy Sylvis, a 41-year-old real-estate investor with cystic fibrosis in Los Angeles, said she was prescribed antibiotics about twice a year for almost a decade for lung infections that were misdiagnosed as primarily bacterial. She would feel a bit better and would be sent home but the infection would return. 

“Ironically, the antibiotics probably made the issue worse as it allowed the fungi to grow and become more prevalent,” she said. 

It wasn’t until Ms. Sylvis read about Aspergillus on online forums for people with cystic fibrosis, a genetic disorder that damages the lungs and digestive system, that she said she pressured her doctors to test her for it. She said she was relieved to finally pinpoint a source of her suffering. 

“I’d missed out on a lot of life,” she said. 

Write to Dominique Mosbergen at dominique.mosbergen@wsj.com