The idea of deadly fungi might conjure up images of poisonous red mushroom caps with distinctive white spots – or sneaky false morels that can turn a fun day of foraging into an evening of gastrointestinal distress.

But in reality, the most deadly fungi on the planet are practically invisible to the human eye!

The World Health Organization, in response to the rising threat of invasive fungal disease, released a list of priority fungal pathogens on Oct. 25 – and the most dangerous ones might surprise you. They're all microscopic fungi, some of which have the potential to kill.

"Fungi are the 'forgotten' infectious disease. They cause devastating illnesses but have been neglected so long that we barely understand the size of the problem," said Dr. Justin Beardsley, of the University of Sydney Infectious Diseases Institute, in a statement. Dr Beardsley was among the researchers supporting the WHO Fungal Priority Pathogens List's development.

The priority list breaks down 19 of the most common fungal pathogens into three priority tiers based upon surveys and discussions with fungal infectious disease experts. The most dangerous is the "critical group," which contains just four fungal pathogens: Cryptococcus neoformans, Aspergillus fumigatus, Candida albicans and Candida auris.

Cryptococcus and Aspergillus are both invasive fungi that can infect the lungs, causing pneumonia-like symptoms that can progress into more severe sickness. Candida albicans normally lives on the skin and inside the body without causing any problems. But if it starts to grow out of control, it can result in thrush of the mouth and throat or a vaginal yeast infection, also known as vaginal candidiasis. Candida auris is an emerging fungal threat, with very little known about it so far. But it's often multidrug resistant and has caused serious outbreaks in healthcare facilities.

The ranking of fungal pathogens was decided by experts who weighed the impact of the fungal disease on public health and how much research and development has been given to the fungus so far.

The list was inspired by and follows in the footsteps of the 2017 Bacterial Priority Pathogens List, which the WHO used to help direct resources to bacterial infections that were the most under-researched and posed the greatest threats to global health. The hope is that now with the release of the Fungal Priority Pathogen List, policymakers will have guidelines in place helping them to direct resources toward dealing with the highest priority invasive fungal pathogens.

Infectious fungi are opportunists

While many of us think that most fungi out there are dangerous (with a small minority being edible), it turns out that most fungi don't affect people at all. A recent study estimates that of the 150,000 fungal species described, only about 200 of them are infectious to people.

Those fungi that are infectious are often opportunistic pathogens – meaning we live with or near them all the time, but they only cause an infection in people who have weakened immune systems.

Take Aspergillus fumigatus, for example. It's a relatively common fungus that can be found in decaying leaf litter nearly everywhere. Michelle Momany, a fungal researcher at the University of Georgia who studies Aspergillus, says that current research estimates that "every one of us inhales between 10 and 100 Aspergillus spores a day."

The way that invasive fungal infections spread is very different from other infectious diseases. "These fungal infections, when you get them, it's not from another person, you get them from the environment," says Momany, who was not involved in the creation of the priority list.

For most people, this isn't a big deal, but for others it could be deadly. "While an intact human immune system can easily fend off these fungal pathogens, those who are immunocompromised can't, which might lead to a clinical infection," Momany says.

The burden of infections

Despite the fact that many of these fungal infections are relatively common, the WHO report says a lack of data means it's impossible to estimate the exact burden these diseases have on the global population.

"Some of the best estimates out there say at least 1.5 million deaths a year are caused by invasive fungal infections. That's on the same order as malaria. But people don't think about fungal diseases in the same way," says Momany.

Momany suggests that part of the issue is a lack of awareness on the part of clinicians, and not having the proper diagnostic tools might mean fungal infections aren't discovered when a patient comes in with an infection. "Oftentimes [fungal diseases] are diagnosed on autopsy, which leads to the problem of them being underreported," she says.

But the release of this priority list might help bring more attention and resources to creating new diagnostic tools, new treatments, and better training for clinicians. Dr. Orla Morrisey, co-chair of the Australia and New Zealand Mycoses Interest Group, said in a statement that, "this project has really focused the global mycology community on the task ahead."

Antimicrobial resistance

The release of the list comes on the heels of an ever-growing number of invasive fungal diseases along with antimicrobial resistance becoming more common in invasive fungi.

WHO Assistant Director General of Antimicrobial Resistance, Dr. Hanan Balkhy, says, "Emerging from the shadows of the bacterial antimicrobial resistance pandemic, fungal infections are growing, and are ever more resistant to treatments, becoming a public health concern worldwide."

One of the first tools that clinicians turn to when fighting a fungal infection are a class of antifungal drugs called azoles. But as usage has increased, invasive fungal pathogens have adapted and become resistant, just like many bacterial diseases have become resistant to antibiotics.

Unlike bacterial resistance to antibiotics though, the source of this antifungal resistance can be partially explained by environmental usage of antifungals. "One of the major fungicides used to protect crops from fungi is an azole. It's now become pretty clear that agricultural use is driving some of the clinical resistance," says Momany.

Morrisey calls for further investment into basic research, saying that, "this is the key to developing new drugs and diagnostic tests," which might help detect and treat antifungal resistant infections.

Hopefully, the release of the priority list will bring more attention and resources to dealing with these invasive fungal pathogens. Momany says, "What's great about [the release of the priority list] is to have it all pulled together now in a way that can inform policy. Having the World Health Organization tracking it now and bringing attention to it is just huge."

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