Fungal Infections of Clinical Importance

FROM THE LECTURE SERIES: An Introduction to Infectious Diseases

By Barry C. Fox, M.D., University of Wisconsin

There are several fungal infections that have significant clinical importance. A person can end up in several situations that could place them at the risk of acquiring a fungal infection. There are many fungal diseases that are unique to particular areas of the United States and Cryptococcus neoformans, a yeast, is found in the soil throughout the United States.

3-D image of the Cryptococcus neoformans yeast.
When inhaled by individuals, Cryptococcus neoformans, which is a yeast, can lead to pneumonia and serious infection around the brain or spinal cord, known as “fungal meningitis”. (Image: Kateryna Kon/Shutterstock)
Note: All information and data below is current as of the publication date of this article. For up-to-date statistics and further information about White-Nose Syndrome, please visit the White-Nose Syndrome Response Team website.

Cryptococcus Neoformans

Cryptococcus neoformans is a yeast that is found in the soil throughout the United States. When inhaled by patients with compromised immune systems, it can lead to pneumonia and serious infection around the brain or spinal cord, known as “fungal meningitis”.

Cryptococcus has a very thick-walled, sugar-based capsule that prevents white blood cells from attacking and destroying the yeast. Hence, aggressive antifungal therapy is required to successfully treat this dangerous and often life-threatening condition.

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The 2012 Outbreak of Fungal Infections

In September 2012, a multistate outbreak of fungal meningitis and infectious arthritis was detected in eastern United States. Over 700 patients who received steroid injections, produced by a single pharmaceutical compounding center, developed meningitis or spinal infections. More than 30 patients who received injections into the joints, like knees, developed the same infections.

The cause of this infection was traced to Exserohilum species, a brown-black fungus. The injections were being given for pain since steroids reduce inflammation and pain, shutting down the body’s immune response at the site of the injection. The average time from the injection to the beginning of symptoms was 18 days.

Further epidemiologic investigation revealed that the risk of infection was associated with specific batches of the steroid and older vials. The more injections individuals received, the larger the volume of the steroids and the greater the risk of infection.

Actions Taken to Control the 2012 Outbreak

Image of a colony of Exserohilum turcicum on PDA agar.
In September 2012, a multistate outbreak of fungal meningitis and infectious arthritis was detected in eastern United States which was caused by Exserohilum species, a brown-black fungus. (Image: Kallayanee Naloka/Shutterstock)

As the risk of infection grew, the Tennessee Department of Health was alerted by a clinician treating a patient with this unusual form of meningitis. With information rapidly communicated from Tennessee, the Centers for Disease Control reached out to state and local health officials and took collective action.

Within days, the source of the outbreak was identified, and a massive effort was undertaken to identify and contact nearly 14,000 potentially exposed patients and their physicians across 23 states. Voriconazole, an antifungal medicine, was used to treat most patients, but some were also treated with a more advanced antifungal medicine called Amphotericin B.

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Common Molds That Cause Infections

There are thousands of fungal mold spores, floating around in the air that are invisible to the naked eye. Normally, the immune system of humans is sufficiently strong to fight the occasional spores that land in the lungs that may cause infection. In patients with compromised immune systems, these spores can enter the lung and cause a fungal infection of the lung.

One of the most common molds to cause infection in immune-compromised patients is Aspergillus. This is a critical problem with transplant recipients, as up to 5 percent of transplant patients may die from invasive fungal infections when the Aspergillus is inhaled into the lung and the immune system cannot compensate.

For the normal immune system, some individuals may manifest non-life threatening, yet annoying allergic symptoms from mold, such as hay fever allergies.

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Antifungal Drugs

The prototype antifungal medications are known as azole drugs. They interrupt the cell wall synthesis in fungi, blocking ergosterol production and leading to the incomplete synthesis of the cell wall. Since fungi do not replicate as quickly as bacteria, and they have a slower growth rate of metabolism, antifungal therapy needs to be continued for longer than antibiotics.

Two other antifungal drugs used for systemic infections are the echinocandin medications and amphotericin. Echinocandins disrupt the cross-linking of the fungal cell wall. Amphotericin directly attacks the fungal cell wall, leading to alterations in the permeability of the cell wall, and subsequent fungal cell death.

White-nose Bat Syndrome

White-nose bat syndrome is a fungal disease of hibernating bats that started in northeastern United States and is spreading rapidly into the central United States.

So far, it has affected 12 bat species. Since this syndrome was recognized in 2007, millions of insect-eating bats in at least 35 states and seven Canadian provinces have died. The infestation gets its name from a white fungus, “Pseudogymnoascus destructans” that grows on the muzzle, wings, and ears of hibernating bats.

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White-nose Bat Syndrome in the United States

The economic effect on insect suppression by bats to U.S. agriculture is valued in billions of dollars per year. The true ecological consequences are not yet known.

Bats are major consumers of insects, and an increase in these pests could result in damage to crops and forests, and lead to a need for increased pesticide applications. Bats also play crucial roles in plant pollination, seed dissemination, and cave ecosystems.

Bat guano is often the basis of the cave’s food chain among animal and plant species. It’s estimated that there has been a loss of almost 80 percent of the bat population in the north-eastern U.S. since the white-nose syndrome appeared.

Effect of Fungal Diseases on Plants

Image showing fungal disease on plants.
In 2014, a fungus known as Leaf Rust nearly destroyed the coffee bean known as Arabica in Central America. (Image: JGade/Shutterstock)

Fungal diseases on plants can have a great impact on our lives.

In 2014, a fungus, known as the Leaf rust, nearly destroyed the coffee bean known as Arabica in Central America. Leaf rust is a fungus that chokes the coffee plants as they grow.

The fungus seems to have a predilection for the Arabica coffee bean, which accounts for 75 to 80 percent of the world’s coffee production. It seemed that slightly higher temperatures in Central America have allowed the fungus to thrive at higher altitudes where this coffee bean grows best.

Common Questions about Fungal Infections of Clinical Importance

Q: What is Cryptococcus neoformans?

Cryptococcus neoformans is a yeast that is found in the soil throughout the United States.

Q: What are prototype antifungal medications?

The prototype antifungal medications interrupt the cell wall synthesis in fungi, blocking ergosterol production and leading to the incomplete synthesis of the cell wall.

Q: What is the White-nose bat syndrome?

White-nose bat syndrome is an emerging fungal disease of hibernating bats that started in northeastern United States and is spreading rapidly into the central United States and Canada.

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