Fungi researcher Marieke Ramsey rises before dawn and puts on heavy long pants and hiking boots thick enough to stop a snake bite, keeping an N95 mask handy for a microscopic hazard that can be as dangerous as snake venom. Several times each summer she makes the long drive from her home in northern Arizona’s high country down to the lower elevations of the Sonoran Desert outside of Phoenix or Tucson.
Hiking beneath giant saguaro cactuses and around creosote bushes, Ramsey searches for animal burrows. “I’ve been to rat burrows and ones with badgers, rabbits, even squirrels,” she explains. “In fact, any burrow used by a mammal will do.”
When Ramsey finds a burrow, she puts on the mask and collects samples of dirt from a few inches below the surface and spoons them into plastic specimen cups for later analysis.
She’s looking for coccidioides, a fungus that causes a disease called coccidioidomycosis, better known as valley fever. If inhaled, microscopic spores from the fungus can lodge in the lungs. About a third of those infected with cocci never have any symptoms, and most of those infected clear the disease and develop immunity. But for between 1 and 5% of those who inhale it, cocci spreads through the bloodstream and wreaks havoc in the body that can sometimes be lethal. And the changing climate has allowed valley fever to spread far beyond its traditional territory of Arizona and parts of Southern California.
“We’re watching the valley fever endemic area expanding from the Southwestern U.S. all the way up to the Canadian border by the end of the 21st century,” Morgan Gorris, a staff scientist at Los Alamos National Laboratory in New Mexico, reported at a recent workshop on the disease.
Sound familiar? It might, at least to fans of “The Last of Us,” the popular 2023 HBO post-apocalyptic drama.
“I loved that series!” Ramsey says, recalling the opening scene in which a character called Dr. Neuman, an epidemiologist, says on a talk show that the fungus cordyceps can hijack the brain of a living ant and control the insect “like a puppeteer with a marionette.” Another expert dismisses any threat to humans, whose higher body temperature is lethal to the fungus. Then Neuman asks, ominously: “What if the world was to get slightly warmer?”
With climate change, he notes, we could be one mutated gene away from a dystopian world with billions of zombified victims seeking “to spread the infection to every last human alive.” Neuman notes that vaccines against fungi “don’t exist. It’s not even possible to make them.”
“The threat posed by fungi in a warming world is exactly what we need to be thinking about,” says Dr. Bridget Barker, director of the lab at the Pathogen and Microbiome Institute at Northern Arizona University where Ramsey works as a researcher.
Rebecca Hamblin-Thompson of Mission Vejo, California, thinks about the danger nearly every day. In May 2018, she and her husband were in their garage south of Los Angeles, unpacking boxes from a two-year stay in Phoenix. The flaps of a box popped up as she was opening it, spraying dust particles inches from her face. She was momentarily annoyed but moved on with her work. Then, two weeks later, she woke up coughing.
“I just thought, ‘Oh, I’ve got the flu and it has to run its course,’” she said. But two weeks later, she felt worse. An urgent care center diagnosed bacterial pneumonia, gave her an antibiotic, and sent her home, yet her health declined further. She was constantly exhausted and the coughing became so bad her rib cage ached. “It was just relentless,” she remembers.
Rebecca returned to the urgent care and an X-ray revealed a white circle in one lung. They referred her to a pulmonologist, or lung specialist. A CT scan showed the circle was a cavitary lesion, “a hole in my lung.” The doctor thought it could be cancer, or something else.
“To be honest,” Rebecca says, “no one had a clue what was happening to me. I cried in the car on the way home.” Several weeks and more trips to doctors later, she was finally diagnosed with valley fever and began taking a powerful antifungal medicine.
“Unfortunately, that’s the classic scenario,” says Dr. Gerardo Gomez, an infectious disease specialist at Banner-University Medical Center in Phoenix. “People will have terrible symptoms for two or three weeks or more. They’ve made at least one or two trips to their doctor or to urgent care, but their diagnosis has been missed. Everyone gets an antibiotic and they’re sent home. And then they just get worse, because they’re being treated for a bacterial infection. But the real problem is the coccidioides, and most doctors have never heard of it.”
In the U.S., coccidioides was known to be endemic primarily in Arizona and California. While travelers passing through these areas sometimes contract valley fever, about two-thirds of all reported cases of the disease are in Arizona.
Now more doctors are hearing about valley fever because the disease is spreading outside of coccidioides’ traditional hot spots.
Gorris, the scientist at Los Alamos, created the first valley fever incidence database and, using known temperature and precipitation ranges in disease hot spots, found that the fungi’s environmental niche turns out to be a mean annual temperature level above 51 degrees Fahrenheit and precipitation below 24 inches a year.
“Now, 51 degrees doesn’t seem very hot,” she said, “but you have to remember we’re taking an average over a whole year, and also averaging out the high and low temperatures for that day. So it’s quite warm.”
Gorris combined those parameters with climate change projections and used advanced computer modeling to produce a series of maps of the United States showing the expected spread of valley fever over time.
What she found was alarming.
“The valley fever endemic area expands from the southwestern United States all the way up to the Canadian border by the end of the 21st century,” she said. Already, climate change is thought to have expanded the disease’s range into the Pacific Northwest and northward in Nevada, Utah, and New Mexico.
Gorris calculated that climate change is expected to increase valley fever case numbers by 12% over the next decade. By 2095, that number would increase up to 50%. If expected population change is factored in, the number of people living in these valley fever-prone areas could grow from about 50 million to as many as 80 million by the end of the century. All other factors being equal, the incidence of valley fever cases would increase at the same high rate.
But according to the most recent studies, all other factors may not be equal, as researchers are still learning how coccidioides develops.
The current hypothesis is known as “grow and blow.” The moisture from winter rains allows the fungus to grow into filaments under the soil. Parts of the filaments break off into single cell spores that lie inert just inches deep. When desert soil is disturbed, spores are brought to the surface. During the hot, dry summer, winds sweep across the desert floor, lifting spore-laden dust into the air. Their microscopic size, 15 trillion spores per cubic inch, allows them to stay aloft at great heights and travel long distances. If they descend over populated areas, a single inhaled spore can cause valley fever.
NAU mycologist Bridget Barker believes there may be more to their story.
“Around 150 million years ago,” she says, “an ancestor of coccidioides emerged. It most likely would have been a plant eater.”
At some later point the organisms diverged. “The new group evolved enzymes that digest more animal proteins,” she says, hypothesizing that the mass extinction of the dinosaurs could have driven the mutation. Whatever the cause, the resulting meat-eating fungus made the jump to mammals, resulting in the coccidioides that causes valley fever today.
But mammals, like rats for example, may serve as intermediate hosts, raising another possible avenue for valley fever to expand its range. As the climate changes, animals often migrate, allowing rats infected with cocci to introduce valley fever into new areas.
Our changing climate is causing a host of other secondary effects which could increase the spread of valley fever even more, says Barker.
“The unpredictability and severity of storms, particularly hurricanes and tornadoes, bring up a lot of dust,” she says, “and that could transport the organisms long distances, potentially exposing people who have never been at risk for valley fever.”
Barker is considering the possible need to add “flow” to the grow and blow theory: “The movement of water across the desert landscape could be another way that cocci travels from one place to another.”
She explains that the spores are repelled by water molecules, so they float on the surface.
In the desert Southwest, long dry spells are followed by short but intense storms that can dump several inches of rain in one hour. The hard desert ground can’t absorb all the water and it runs into washes, low-lying channels. Particularly powerful storms drive floodwaters into far away rivers, which drain into the Pacific Ocean. Some level of infection has been found in sea otters and other marine mammals off the coast of California.
Changing rainfall patterns linked to climate change have caused historic flooding, most recently from a series of atmospheric rivers that drenched California. Researchers fear that these changes in rainfall, along with record heat waves, may allow cocci to take hold and take off in areas where the fungus was once rare or entirely absent.
Climate change is also driving explosive growth in wildfires globally. In the arid West, “fire season” is becoming a year-round phenomenon. Besides mounting deaths and illnesses from breathing wildfire smoke, wildfire smoke may be spreading spores that cause valley fever.
“The length of fire season is increasing,” noted Leda Kobziar, professor of wildland fire science at the University of Idaho and part of a team that recently began pioneering work using drones to collect samples from wildfire smoke plumes and analyze them for pathogens. Cocci has not been found, but the pathogenic fungus Aspergillus fumigates was found in a smoke flume, and it produced an infection in laboratory mice.
While much remains a mystery, no one understands the big picture better than Dr. John Galgiani, an infectious disease doctor and director of the Valley Fever Center for Excellence at the University of Arizona’s College of Medicine in Tucson, which he founded in 1996. Mycologist Bridget Barker calls Galgiani “the undisputed leader on the clinical side.”
Galgiani stresses that most people who test positive for coccidioides never have any symptoms. But within that small group of people who get valley fever, certain groups are overrepresented. Women diagnosed during pregnancy, especially in the third trimester, are more likely to have the fungus spread beyond the lungs with potentially serious ramifications. Also, Galgiani noted: “People who identify as African American or Filipino have higher rates of dissemination compared to those who identify as white.” But Galgiani warns against complacency by anyone.
“Just walking around the streets in Phoenix puts you at risk of getting the disease,” he says. “You’ll most likely never know it. But it can develop into a serious disease.”
Dr. Gerardo Gomez, an infectious disease specialist at Banner-University Medical Center in Phoenix, has a hunch that homelessness could be another risk factor.
“We see a big proportion of homeless people with respiratory symptoms here and they usually have valley fever.” Living unsheltered on the streets and being exposed on a nearly constant basis to dust that contains spores, Gomez says, would be a likely link.
The standard treatment for those serious cases is the antifungal medicine fluconazole, which can limit the growth of cocci, but not eliminate it.
“None of the treatments we have can cure this disease,” says Galgiani, “they just suppress it.”
Like many other patients who have suffered valley fever, Rebecca Hamblin-Thompson is aware that suppression is the best one can currently hope for. When she was finally correctly diagnosed, she says, the level of fungus in her blood was high enough to begin spreading throughout her body. She began taking fluconazole and the cough ended a month later and she was able to stop the medicine. Nearly two years later, after inhaling smoke from wildfires, Rebecca developed what was at first diagnosed as a sinus infection.
“But then all my symptoms from valley fever returned and I had to start back on fluconazole,” she says. “It was devastating to go through all that again.”
Through the center he founded, Galgiani has been working for years to create a vaccine that would prevent cocci infection. It’s a tall order. As the fictional Dr. Neuman pointed out in “The Last of Us,” antifungal vaccines do not exist.
But that may be about to change.
“This is so cool,” says Galgiani, leaning forward in his chair as he describes how University of Arizona fungal geneticist Marc Orbach and veterinary research scientist Lisa Shubitz met through the Valley Fever Center for Excellence and began exploring how a vaccine might work. Orbach found that by removing a certain gene in coccidioides the fungus survives but loses its virulence. When Shubitz put the genetically altered fungus into immunodeficient mice, it began to grow but then fell apart. “It’s a live organism,” says Galgiani, “that doesn’t cause disease.” The person who receives the vaccine would be immune to valley fever.
With adequate funding, Galgiani estimates that the vaccine could begin testing on humans in four years, and, if safe and effective, become widely available in another four, making it the first vaccine against a pathogenic fungus.
Many such advances will be needed in a warming world, says Dan Ferber, a science writer and editor at Springer Nature. Along with the late Dr. Paul Epstein, Ferber co-authored the 2011 landmark book, “Changing Planet, Changing Health.”
Asked about valley fever, Ferber says, “That particular disease wasn’t on our radar, but the climate-driven expansion of sickness very much was — including the health impacts of desertification and dust-borne illnesses.” Ferber and Epstein say in their book that even the best adaptations such as vaccines for individual diseases are insufficient to solve the larger problem. We have to stop burning fossil fuels.
“Just as an ailing patient can recover, so can an ailing planet,” Epstein wrote in his introduction to Changing Planet, Changing Health. “But we must act now.”
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