Fungi That Nobody Wants to Invite to a Party

“US study shows rising prevalence of fungal infection.”

Chris Dall, MA, news reporter, CIDRAP News

“Genetic mutations are driving an increase in the variation of triazole-resistant genotypes and phenotypes of Aspergillus fumigatus.”

Heidi Splete, American journalist

You may have heard the joke: “Why did the mushroom get invited to all the parties? Because he was a fungi (fun guy)!” Most fungi are either harmless or beneficial to humans. Yet, there are fungi that no one wants to invite to a party. In this week’s post, I draw attention to developments involving four pathogenic fungi: Histoplasma, Coccidioides, Candida, and Aspergillus.

What are fungi? (a recap). Fungi are eukaryotic organisms, meaning their cells contain a true nucleus and membrane-bound organelles. They are classified into the domain Eukarya (or Eukaryota), in contrast to Bacteria and Archaea. Fungi belong to their own distinct kingdom and are characterized by having chitinous cell walls and a filamentous structure. Kingdom Fungi includes molds, yeasts, and mushrooms.

There are an estimated 3.5-5.1 million fungal species on earth but only 300 are human pathogens. Of these pathogenic fungi, approximately 20-30 species cause the vast majority—greater than 90%—of serious human fungal infections.

Most of the world’s described 157,000 fungal species are only visible with a microscope, the mushroom being an exception. The largest single living organism on Earth, by biomass, is a subterranean honey mushroom. Dubbed “the humongous fungus,” Armillaria ostoyae is found in Oregon, covers 2.384 acres (~3.7 sq. miles) of the forest floor and is still growing.

Trouble with yeasts. Histoplasma capsulatum (H. capsulatum) is a dimorphic fungus, meaning it exists as a mold in the environment and converts to yeast (or yeast-like spherules) in human tissue. This fungus likes moist soil, particularly that enriched by decaying guano. When H. capsulatum is disturbed, the conidia (spores) become airborne and can be inhaled and cause a granulomatous inflammation resulting in histoplasmosis, a pulmonary disease similar to pulmonary tuberculosis. The symptoms of pulmonary histoplasmosis included headache, fever, cough and muscle pains.  Histoplasmosis can lead to considerable morbidity and mortality for immunocompromised patients but is rarely seen in immunocompetent patients.

On January 17, 2025, a cluster of 12 cases of cave-linked histoplasmosis was reported to the Centers for Disease Control and Prevention (CDC). The patients, all part of an extended family living in Georgia, Texas and Washington, had visited the Venado Caves in Costa Rica together and reported direct exposure to bat droppings. (The Venado Caves had been associated with an histoplasmosis outbreak in 1998-1999 involving 51 patients.) Upon returning home, 8 to 19 days post exposure, the patients developed symptoms of pulmonary histoplasmosis.

Travel history was not initially elicited from the patients in most of these cases. As a result, fungal infections were not considered in the differential diagnosis. This led to the prescription of antibiotics, corticosteroids, or symptomatic treatment. (“Cave-linked histoplasmosis cluster underscores need for travel history in diagnosis,” Morbidity and Mortality Weekly Report, May 22, 2025). The CDC suggests this outbreak underscores the importance of obtaining a thorough travel and exposure history, including exposure to bat or bird droppings in caves or elsewhere.

Coccidioides is also a dimorphic fungus; it is endemic to the southwestern U.S., northern Mexico and areas in Central and south America. Coccidioides immitis and Coccidioides posadasil are the two species of Coccidioides that cause the disease coccidioidomycosis (Valley Fever). This respiratory infection is typically caused by inhaling arthroconidia which often become airborne after contaminated soil is disturbed.

Typical symptoms of pulmonary coccidioidomycosis include fatigue, cough, shortness of breath, chest pain, headache, night sweats, muscle aches or pains, and rash. Primary pulmonary disease is often self-limiting but a small percentage of patients fail to recover fully and develop complications or chronic pulmonary disease.

Concern continues to grow regarding the mounting number of pulmonary and central nervous system infections due to Coccidioides immitis that are seen mainly in California and other states in Southwestern U.S. In 2025, a CDC-led analysis estimated that the true burden of symptomatic coccidioidomycosis in the U.S. may be 10 to 18 times higher than reported. (Anderer, S., “Valley Fever Likely Vastly Underreported,” JAMA, June 27, 2025.) As Mitsuru Toda, PhD, an endemic fungal expert in the CDC’s Mycotic Diseases Branch said, “Some of the main factors contributing to underreporting include under-diagnosis or misdiagnosis of coccidioidomycosis as bacterial or viral community-acquired pneumonia. Also, coccidioidomycosis is reportable only in 28 states and Washington, DC, and people may not seek care for coccidioidomycosis even if they have symptoms.” (Abene, S., “CDC Estimates True Valley Fever Burden May Be Up to 18 Times Higher Than Reported,” Contagion Live, June 12, 2025).

Candidiasis is a fungal infection caused by yeasts that belong to the genus Candida. Candida albicans (C. albicans) and Candid auris (C. auris) are two of these yeasts.

C. albicans is an opportunistic pathogen that resides in the gastrointestinal tract and oral and vaginal mucosa of most, if not all, healthy individuals. As a pathogen, it accounts for a large number of fungal infections occurring in the digestive tract, mucocutaneous tissues and skin as well as in the bloodstream. In most cases, infected individuals are immune deficient or immunocompromised due to conditions such as AIDS or critical illness. Although C. albicans amounts for the majority of Candida infections, C. auris is now capturing more attention.

C. auris was first identified in 2009. Since then it has emerged as a multidrug resistant fungal pathogen that has spread rapidly across 6 continents and into more than 45 countries. (Bazargan, N. “Medscape Now! Candida auris: Risk Factors, Infection Control and Treatment,” Medscape Education, February 23, 2026). It can cause a variety of infections ranging from superficial skin infections to more severe, life-threatening infections, such as bloodstream infections.

There is not a common set of symptoms specific for C. auris infections; instead, symptoms depend on the location and severity of infection. For the most part, C. auris affects patients with severe underlying medical conditions and those requiring complex medical care and invasive medical devices—devices often medically necessary but which create a pathway for the pathogen to get into the body. (Pathways can be created by breathing tubes, feeding tubes, and urinary catheters.)

On March 22, 2023, the U.S. Food and Drug Administration approved rezafungin (Rezzayo) for the treatment of invasive candidiasis and candidemia, including C. auris, in patients with limited or no alternative treatment options. It was the first new antifungal for these infections that had been approved in more than 10 years and has the advantage of weekly dosing as opposed to daily dosing with other antifungal drugs. (Nye, J., “Rezafungin Is Safe and Efficacious Against Adult Candidemia, Invasive Candidiasis,” Infectious Disease Advisor, October 8, 2025).

Trouble with molds. Aspergillus is a filamentous mold found outdoors and indoors, including circulating in the air of hospitals. Aspergillosis is an infection, usually of the lungs, caused by breathing in spores of Aspergillus. Most people do not get sick from inhaling Aspergillus; it can, however, cause severe and deadly infections in people with lung disease or those who are immunocompromised.

There are 250 known species of Aspergillus, but only a small number are known to cause infections in humans. Of these, Aspergillus fumigatus (A. fumigatus) is the most common cause of illness. Infections caused by this opportunistic fungus are becoming increasingly difficult to treat. This is due to emergence of resistance to the antifungal drugs (azoles) that are often used to treat these infections.  (The CDC recently added azole-resistant A. fumigatus to its threat “Watch List.”)

There is, however, a new synthetic antifungal compound, olorofim, that is highly active against A. fumigatus. (Haelle, T., “Novel Agent Succeeds in Tough -to-Treat Invasive Fungal Disease,” MedPage Today, June 21, 2025). It is the first orotomide antifungal agent to be developed and is active against fungi that are resistant to other therapies.

The costs of fungal infections. Fungal diseases are increasing worldwide due to a multitude of factors including, but not limited to, climate change and the increase in international travel and trade. They are also getting harder to treat as they grow more and more resistant to available drugs. Fungal diseases cause around 130,000 hospitalizations, 7,300  deaths and 13 million outpatient visits each year in the U.S. at an annual cost of $19 billion. (“Fungal Disease Burden by the Numbers,” CDC, May 29, 2025). In short, fungal infections are no joke.