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  • Writer's pictureP.K. Peterson

Fungi Are on the Move

“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.”
- Justin Beardsley, MBChB, PhD, Associate Professor in Infectious Diseases, Sydney Institute for Infectious Diseases, leader, World Health Organization Fungal Priority Pathogens List study

“We’ve talked about these [fungi] as zebras … but they’re not zebras. They’re Clydesdales. Clydesdales aren’t the most common horse you’ll see, but they’re still horses.”
- Andrej Spec, MD, MSCI, Associate Professor of Medicine, Washington University School of Medicine, St. Louis

Fungi contribute enormously to the wellbeing of life on our planet. (See my December 1, 2021, Germ Gems post “The Fungus Among Us” where I focused on the benefits of fungi to humans.) They can also, however, be serious pathogens.

About 50 years ago, researchers established specific geographical distributions for certain pathogenic fungi. It now appears that these so-called dymorphic fungi are moving to areas outside their historical distributions. In the last several months, clinical researchers in the U.S. have raised concerns about the geographic spread in the U.S. of the diseases caused by these same dimorphic fungi. And, for the very first time, the World Health Organization (WHO) released a list of invasive fungal infections that are now a major concern worldwide—especially for immunocompromised patients. In this Germ Gems post, I draw attention to these two events and consider the impact they may have on the diagnosis and treatment of fungal infections.
The threat of dimorphic fungi in the U.S. expands. A large majority of the billions of species of fungi are microscopic and come in one of two forms: yeasts or molds. Yeasts are single-celled microbes, best known for their role in baking and beer and wine making. Molds are fungal forms that grow and spread on varying kinds of damp or decaying organic matter. (You’ve likely encountered one growing on a moldy orange or bread.)

There are also dimorphic fungi. During their life cycle, dimorphic fungi have the ability to switch between hyphae (molds) and yeasts. The switch in morphology is usually brought about by change in temperature: a mold at room or ambient temperature becomes a yeast at human body temperature.

Coccidioides immitis, Histoplasma capsulatum, and Blastomyces dermatitidis are three dimorphic fungi. In nature they are found as molds in soil, and when their spores are released and inhaled, they assume a yeast form in the lungs and elsewhere when they disseminate to other body sites.

In the article, “The Geographic Distribution of Dimorphic Mycoses in the United States for the Modern Era,” published in the November, 2022 issue of the journal Clinical Infectious Diseases, the authors raised concern about these three dimorphic fungi. The researchers carried out a retrospective analysis of records of more than 45 million Medicare beneficiaries from January 2007 through December 2016. Their key finding was that people with the three diseases caused by dimorphic fungi (coccidiomycosis, histoplasmosis, and blastomycosis) were diagnosed in significant numbers outside their historical geographic distributions established more than 50 years ago.

This means, for example, that coccidiomycosis, otherwise known as “cocci” or alternatively “Valley Fever” in light of its concentration in the San Joaquin Valley of California, cropped up in 33 states in addition to California and Arizona (known hotbeds of the disease). The same expanded distribution was also found for histoplasmosis. It was no longer confined in the U.S. to the Midwest and parts of the East and South, but now was reported in 47 states and Washington, D.C. And blastomycosis, traditionally found in midwestern and eastern states, was now diagnosed in 40 states.

The basis for the expansion of the ranges of all three dimorphic fungi isn’t entirely clear. Global warming associated with climate change likely is involved. Warmer environments generally foster growth of soil-bearing fungi. Also, as is the case with many emerging infections, travel could explain some of the increase in cases.

Change in distribution maps and increased awareness. In her November 28, 2022 article in Smithsonian Magazine, “Fungi That Cause Lung Infections May Be Spreading Across the U.S.,” journalist Sarah Kuta wrote, “[D]octors are likely to misdiagnose cases due to outdated maps of these fungi’s ranges.” It is important, therefore, that clinicans, as well as public health officials, overhaul the maps of the distributions of C. immitis, H. capsulatum, and B. dermatitidis. In addition to updating the distribution maps of these three dimorphic fungi, the most important outcome intended by this study is heightened awareness (“index of suspicion”) of fungal disease in the minds of clinicians who see these patients.

Not uncommonly, patients with dimorphic fungal infections of the lungs are treated initially with antibiotics for bacterial pneumonia. This is ineffective and delays antifungal treatment while the yeasts disseminate to other organs, such as, the brain, bones, and skin. When caring for patients with pneumonia, dimorphic fungal infection should now be routinely considered.

Fungal infection as a global health threat. In response to the rising threat of invasive fungal disease worldwide, on October 26, 2022 the WHO released its first ever list of threatening fungal infections. (This announcement more or less coincided with the Clinical Infectious Diseases publication on increased awareness of the range of dimorphic fungal infections in the U.S.) The WHO’s 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 “Critical Priority Group” contains four fungi: the mold Aspergillus fumigatus, and three yeasts: Cryptococcus neoformans, Candida auris, and C. albicans. The dimorphic fungus, H. capsulatum, is in the “High Priority Group,” and C. immitis is in the “Medium Priority Group.” (B. dermatitidis didn’t make the cut.)

What the 19 fungal species in the “WHO’s Priority Pathogens List” have in common is that they’re all opportunistic pathogens, meaning they are a major threat to people who are immunocompromised. A. fumigatus, for example, is the bane of organ and bone marrow transplant recipients.

Some of the fungi in the WHO’s priority list, like C. auris, are resistant to most currently available antifungal drugs. Fostered by global warming, this fungus is spreading rapidly around the globe where it is terrorizing patients in intensive care units in many countries. WHO’s rationale behind releasing its priority list is to help bring more attention and resources to improved diagnostic tools and treatments of fungi. As was stated in the journal Nature this February, “The WHO fungal priority pathogens list is a ‘game-changer’.”

Fungal research is also on the move. Cancer patients are one of the largest groups of immunocompromised hosts who are at risk of opportunistic fungal infections. In a Medscape Oncology article in October 2022, “Fungi Inside Cancer Cells: ‘A New and Emerging Hallmark,’” a remarkable discovery is highlighted. On September 29, 2022 in the prestigious journal Cell, Lian Narunsky-Haziza, PhD and his colleagues at the Weizmann Institute of Science in Rhovot, Israel reported finding numerous fungal species in tumors of 35 different cancer types.

As stated by study co-author Rob Knight, Ph.D., a professor at the University of California San Diego, the existence of fungi in most human cancers “is both a surprise and to be expected. It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected, because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth, and skin, where bacteria and fungi interact as part of a complex community.”

I’m sure that we’ll be hearing a lot more about the cancer mycobiome in the future. So too, with the increased attention on the pathogenic as well as beneficial roles of fungi, we’ll be learning more about other amazing characteristics of these incredible creatures.
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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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