Issue No. 20: Fungal Infections on the Rise

The global conversation over antimicrobial resistance (AMR) often focuses on bacterial infections. While these do constitute a serious threat, other kinds of treatment-resistant microbes also need public-health attention. In particular, drug-resistant fungal infections are on the rise — and patients with conditions like cancer, HIV, and Covid-19 are at elevated risk.

Did you know? Most of us inhale between a thousand and 10 billion fungal spores every day, and many fungi live in our bodies benignly. Normally, our immune systems protect us from fungal infections.

But in recent years, the number of these infections has risen considerably. Currently, more than 300 million people around the world suffer from fungal infections, which kill about 1.6 millionpeople a year. In the United States, about 7,200 people died from a fungal infection in 2021, up from 450 in 1969 — a 16-fold increase over a half-century.

Unfortunately, our understanding of drug-resistant fungi is limited. But a recent study from the World Health Organization (WHO) aims to change that. Released last fall, it lists 19 fungi of top medical concern and brings much-needed urgency to an escalating crisis. As the report notes, efforts to address the problem have been stymied by shortages of antifungal treatments, diagnostic tools, reliable data, and research funding.

The world needs to address the looming catastrophe of antimicrobial resistance as a whole, with efforts that include tackling bacterial disease as well as the less-understood world of fungal infection. As University of Sydney infectious disease expert Justin Beardsley recently said, “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.”

The WHO report illuminates his point. For each of the high-priority fungal pathogens it identifies, there is a dearth of data on the burden of disease. An acute shortage of diagnostic tools has widened the knowledge gap. Specialized labs that provide tests for fungal infections exist in fewer than 20 countries. The paucity of information available to scientists and doctors makes it hard to mount an effective response.

Fungi and AMR

The current fungal threat emerges from two separate but interconnected crises: Fungal diseases are rising overall, especially among patients with compromised immune systems. At the same time, we’re seeing an alarming growth in fungi that are resistant to available treatments. This second challenge — a part of the larger AMR crisis — makes fungal infections far more difficult to treat.

Like a bacterium, when a fungus is repeatedly exposed to a medicine designed to kill it, it evolves and can eventually become impervious. That is why, over time, once-effective drugs lose their power. Worse, there are only four distinct classes of antifungal medicines available at the moment, and few new ones in the development pipeline. By one estimate, just 1.5% of research funding for infectious diseases goes toward fungal infections.

The result is a situation very similar to the rise of antibiotic resistance. Both of these facets of AMR — bacteria and fungi — require more public health advocacy, funding, and research.

People with compromised immune systems are most vulnerable to fungal infection. This group includes patients undergoing chemotherapy, transplant recipients taking immunosuppressants, and individuals with HIV.

But others also face a relatively high danger. As the WHO report notes, people with tuberculosis, chronic obstructive pulmonary disease, liver or kidney disease, and even influenza are at heightened risk of fungal infection compared to the general population.

And even healthy people can acquire fungal infections. More and more are catching Valley fever, a sometimes-deadly lung ailment caused by the Coccidioides fungus. Coccidioides has long been present in the soil and dust of the American Southwest. But cases of Valley fever rose more than sixfold in California and Arizona between 1998 and 2018. And whereas the disease was found exclusively in the Southwest in the 1950s, it now exists in at least 35 states. Scientists are exploring dust storms and wildfires as causes for the increase. In total, the United States is seeing about 20,000 cases and 200 deaths each year from Valley fever, mostly still in the Southwest.

The Highest-Priority Fungi

Of the 19 fungal pathogens that pose threats to public health, the WHO identified four as “critical priority,” seven as “high priority,” and eight, including Coccidioides, as “medium priority.” To determine the priority level, the authors used each pathogen’s degree of antifungal resistance as a chief criterion. The pathogens in the critical group are Cryptococcus neoformans, Candida auris, Aspergillus fumigatus, and Candida albicans.

One of the most worrisome among these is Candida auris, a form of yeast first discovered in Japan in 2009 that has proven highly resistant to antifungal drugs. It is sometimes resistant to every class of antifungal, making it alarmingly difficult to treat. In fact, death rates from infections caused by Candida auris are as high as 53%. And this pathogen has been known to cause outbreaks in hospitals.

In the United States, Candida auris infections have multiplied rapidly. Whereas only four states reported clinical cases between 2013 and 2016, as of 2021, nearly half of states had seen at least one case. The Centers for Disease Control and Prevention reported 1,994 clinical cases for the 12 months ending in September 2022 — a more than 11-fold increase since 2017, which saw just 173 cases.

Charting a Path Forward

Like bacterial infections, fungal infections are a public health challenge we can no longer afford to ignore. The WHO report outlines three areas that require action: surveillance, public health interventions, and research and development.

On the surveillance front, the organization recommends significant investment in both laboratory-based and clinical surveillance — not just to identify cases overall, but to understand the extent of antifungal resistance.

Concerning public health interventions, the WHO proposes a broad range of strategies. These include more training for health professionals; better stewardship of antifungal drugs to slow the spread of resistance; policy reforms aimed at improving drug access; and measures to prevent fungal infections before they arise.

Finally, as the WHO observes, it is critical that we ramp up research and development. The world needs more accurate rapid diagnostic tools so that infected patients can benefit from treatment before it’s too late. And doctors need new treatments for fungal infections that no longer respond to existing medications.

A key challenge will be incentivizing companies to invest in new antimicrobial drugs. Lawmakers in the United States could help mitigate the crisis by passing the bipartisan, bicameral PASTEUR Act. The bill addresses a major flaw in the market for antimicrobials: Because these drugs are used sparingly and for short stints, the market for them is small, which discourages private investment. This dynamic is a major reason there are few new antifungals in the drug-development pipeline.

The PASTEUR Act would shift these incentives by establishing subscription plans for new antimicrobials. The government would contract for access, regardless of quantity required, and companies would be assured of a revenue stream. By passing this reform, lawmakers could help stave off the AMR crisis and give hope to millions of patients.

Fungal pathogens are a part of AMR that, until now, has gone dangerously overlooked. The WHO study could mark a turning point. But it also makes clear just how much work has yet to be done — work that needs to start right away.

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