The Last of Us Gets One Thing Right about Fungi and Climate Change

For most of us watching HBO’s The Last of Us on Sunday nights from the comfort of our couch, the show’s postapocalyptic premise feels as distant from our real world as outer space — the slightly chilling parallels to the Covid-19 pandemic notwithstanding.

But The Last of Us’ fictional fungal threat may actually reveal a real-world danger on our warming planet. Let’s get this out of the way first: No, you’re not going to turn into a fungus-ravaged zombie anytime soon. But in the show’s opening episode, scientists explain how global warming could make funguses more of a threat. In the broad strokes — if not the details — the show might actually be right.

“Fungal pathogens are becoming increasingly common and resistant to treatment, and we are only beginning to understand how climate change is contributing to these changes,” Justin Remais, Chair of Environmental Health Sciences at the University of California, Berkeley, and an expert on climate change and infectious disease, tells Inverse.

How Does Global Warming Make Fungi More of a Threat?

“Currently there are no reasons for fungi to evolve to be able to withstand higher temperatures. But what if that were to change? What if the world were to get slightly warmer?” asks one of the scientists in the opening scene of The Last of Us.

“One of the indirect consequences of global warming is indeed the emergence of new fungal pathogens,” William C. Beckerson, a postdoctoral research fellow who studies Ophiocordyceps at Utrecht University, tells Inverse

Pathogenic fungi — which are capable of infecting humans or other animals — evolved to grow in ambient or environmental conditions. As temperatures warm up and come closer to conditions around our body temperature of 98.6 Fahrenheit (37 degrees Celsius), humans will become more suitable candidates for fungal infection. Beckerson explains global warming provides the “perfect storm” of environmental pressure for this fungal evolution to happen.

“As the planet continues to warm, we will see more and more cases of fungal infections,” Beckerson adds.

It’s not just the prospect of new pathogenic fungi that’s scary. Global warming may also increase the likelihood that known fungal pathogens will infect a greater number of humans. A recent paper in Proceedings of the National Academy of Sciences finds that global warming can indirectly trigger a number of genetic changes in the pathogenic fungus Cryptococcus deneoformans, possibly making it more heat-resistant. Climate change is also linked to extreme weather events — natural disasters — and fungal outbreaks have often appeared after natural disasters, such as the explosion of deadly fungus following the 2011 tornado in Joplin, Missouri.

Out of the 150 million severe cases of fungal infections that occur worldwide, roughly 1.7 million end in death, leading some researchers to call fungal disease a “silent crisis.” While the rates of some fungal infections declined between 1999 and 2017, the number of cases of Candida auris — a type of drug-resistant yeast infection — and other fungal infections increased by 10 percent and 30 percent over the same time period, though a link between Candida auris and global warming is scientifically disputed.

But experts say there’s one specific fungal disease that’s almost certainly becoming more of a threat due to climate change — and it’s called Valley Fever.

What is Valley Fever?

Valley Fever — alternatively known as Coccidioidomycosis or desert rheumatism — occurs when humans or other susceptible animals become infected with a spore of the Coccidioides fungus. The fungus gets its name from its origins in the San Joaquin Valley in California, but in the U.S., it’s also widely found elsewhere in the southwestern regions of the country, especially Arizona, where summers are hot and winters more moderate. Valley Fever has also been detected in the state of Washington.

The dominant hypothesis is that this fungus lives in soil. When dust from the soil gets kicked up, the fungus can spread its spores in the air, which people inhale, thereby causing infection. Although it’s a respiratory illness, more common symptoms include aches, pain and fatigue.

According to this soil hypothesis, humans only really get infected by happenstance — if they’re in the wrong place at the wrong time. But other researchers like John Taylor advance an alternative hypothesis, which proposes that the Coccidioides fungus lives in small wild mammals like rodents, depending on them for food and water.

“The [Valley Fever] fungus lives in native rodents. It evolved with them over millions of years,” Taylor tells Inverse. Taylor is a plant and microbial biology professor at UC Berkeley and head of the Taylor Lab, which studies Valley Fever in rodents.

John Galgiani, director of the Valley Fever Center for Excellence, tells Inverse that the fungal spores can linger in the air for long periods of time, so it’s not just outdoor construction workers or people who go dirt-bike riding that are prone to the disease. Anyone living in regions where Valley Fever is endemic — regularly occurring — can get infected. That’s different than other common fungal diseases like Candida auris, which typically infect people with compromised immune systems.

“The [Valley Fever] fungus is unusual in that it can infect otherwise healthy hosts,” Taylor says.

The good news: Valley Fever doesn’t have a terribly high mortality rate. Galgiani says it’s roughly one in every 1,000, and other reports put it at 0.07 percent. Out of the people it infects, roughly two out of three do not become very sick and get better without even treatment. For those who do need medical attention, common anti-fungal drugs will usually help to manage symptoms.

The bad news: Valley Fever cases are on the rise around the country — and there’s no cure for the disease. The CDC reports that roughly 20,000 people became sick with Valley Fever in 2019, but Galgiani believes that’s a significant undercount and that the real number of infections is at least four times higher due to several factors like lack of reporting by infected individuals and physicians misdiagnosing or not testing for the disease. The state of Texas also doesn’t report cases of Valley Fever to the CDC, even though the disease is known to occur there.

“It's a small percentage [of people] that go on to have complications. And those complications can be quite severe,” Galgiani says.

The California Office of Environmental Health Hazard Assessment reports that Valley Fever cases have increased almost fivefold in the state between 2001 and 2021, rising from 4.3 cases per every 100,000 people to a 20.6 per 100,000 in just two decades. Reported Valley Fever cases increased by 32 percent between 2016 and 2018 in the U.S.

Factors like better reporting and more urban development and population growth in places like Arizona — where two-thirds of Valley Fever cases occur — could help explain the rise in cases.

“Valley Fever needs the fungus and human hosts. If there are more hosts close to the fungus, there will be more Valley Fever,” Taylor says.

The Link Between Valley Fever and Climate Change

Several studies have emerged in recent years linking climate change to Valley Fever. A 2017 paper correlated the climate-driven rise in dust storms — which increased 240 percent between the 1990s and the 2000s — to a rise in cases of Valley Fever.

Another 2019 study found global warming will make more places in the U.S. habitable to the fungus responsible for Valley Fever, spreading to dry northern states like Idaho, Wyoming, Montana, Nebraska, South Dakota, and North Dakota. The study projects the number of Valley Fever will double by the end of the century in a high global warming scenario.

But scientists report global warming is also making Valley Fever more troublesome even in endemic regions where it currently occurs like California. Researchers at UC Berkeley analyzed more than 81,000 coccidioidomycosis surveillance records and assessed the link between drought conditions in the state and Valley Fever cases.

“We found that a wet winter, followed by a dry, hot summer, produces conditions suitable for [Valley Fever] transmission,” Jennifer Head, who led the research, tells Inverse. Head is the assistant researcher of Environmental Health Sciences at Berkeley Public Health.

“There has never been a vaccine against fungi of any sort”

Basically: cases decline during drought periods since it’s difficult for the fungus to get nutrients to thrive, but sharply rise in wet periods following dry seasons. During dry periods, fungal chains known as mycelia “lyse” or burst, forming spores that humans can inhale.

It’s unclear why this happens, but Head suspects drought may kill off other soil microbial competitors, allowing the fungus to flourish when rain returns, though global warming may also affect the rodent populations that play host to the disease. In either case, since extreme fluctuations between extreme drought and rainfall are likely to become more frequent under climate change, that means bad news for humans.

“Summers are expected to get hotter and drier. This may result in conditions highly suitable for Coccidioides to grow and spread,” Head says, explaining that the fungus may spread into new, hotter areas of the state due to climate change.

Remais, who served as a principal investigator on the research at UC Berkeley, says there needs to be “focused protections” for people at greatest risk of severe disease, like pregnant women, outdoor workers, adults in older age groups, and those with weakened immune systems.

“We need to better understand how these pathogens are adapting to new environments, and how climate change will influence their future spread,” Remais adds.

Why is Fungal Disease So Hard to Cure?

The prospect of pathogenic fungi spreading to humans more readily is scary because — just as in The Last of Us — there is no clinically approved vaccine for use against fungal infections.

“There has never been a vaccine against fungi of any sort,” Galgiani says.

According to Galgiani, there are three primary reasons why it’s hard to make vaccines for fungal infections:

1. Most fungal infections occur in immunosuppressed individuals, inhibiting vaccine development. “It's hard to create an immunity where there is no immune system to simulate,” Galgiani explains.
2. There are far fewer serious fungal infections reported every year in the U.S. compared to viral or bacterial infections, so there’s less incentive for the government to fund fungal vaccine research. There were some 75,000 reported hospitalizations due to fungal infections in the U.S. in 2014, compared to 970,000 flu-associated hospitalizations in the 2014-15 flu season.
3. We just don’t know enough about fungi. As eukaryotes — organisms possessing a cellular nucleus — fungi are actually more similar to humans than they are to viruses, making them complex to study. Therefore, Galgiania says it's “a more difficult challenge to figure out what part of the fungus is the important part that needs to be used in a vaccine ... Compared to bacterial and viral pathogens, the scientific community knows far less about fungal infections, including how fungi will adapt to a warming world.”

Yet there is hope that a more imminent fungal vaccine is on the horizon. Three fungal vaccine candidates reached human trials in 2021, and, last month, the University of Georgia published research on a vaccine that could protect against the three most common fungal infections, which account for 80 percent of all human fungal diseases in the U.S.

But when it comes to Valley Fever, we’ll likely need to wait years to see a vaccine for human use. Galgiani has been working with the company Anivive on a vaccine that has shown promise in mice and dogs, and he thinks veterinarians will have it available in their clinics in roughly a year. The vaccine works by introducing a live strain of the fungus, but one that has been altered to remove a gene associated with the disease.

“If you use it as a vaccine in a mouse, and then challenge the mouse with an infection with the usual strain with the fungus, mice are protected from that infection,” Galgiani explains, adding “even though it's a live vaccine, it doesn't cause disease.”

Galgiani adds that the vaccine holds promise for humans, but getting funding and approval to do clinical human trials is very “ambitious,” so working towards a vaccine in dogs first made sense since dogs are at even greater risk of Valley Fever compared to humans. If funding weren't an issue, he thinks they could likely complete human clinical trials in six years.

Since people infected with Valley Fever usually do not get sick again with the disease in their lifetime, there’s reason to hope a vaccine would do the same — a concern as climate change means more cases are on the horizon. So there’s probably more hope for a vaccine in real life than in The Last of Us.

“There's a very real possibility that the vaccine for Valley Fever would have very long protection — if not lifelong,” Galgiani says.