Dimorphic Fungi: Histoplasmosis [Hot Topic]

Histoplasmosis

Dr. Glenn Roberts discusses the dimorphic fungus Histoplasma capsulatum, focusing on its distribution, how infection develops, and how laboratories identify it.

Dimorphic fungi and identification

Dimorphic fungi grow in different forms depending on conditions. In culture, they generally appear as molds; in the body, Histoplasma converts to a yeast form.

Growth in culture can take weeks, though the time varies with the amount of fungus in the specimen, the culture medium, and the organism’s metabolism. Adding blood to culture media can help recover some dimorphic fungi. However, organisms that grow on blood-containing media may sporulate poorly and may need to be subcultured onto media without blood.

Microscopic features and colony appearance can overlap among dimorphic fungi. In particular, Histoplasma and Blastomyces colonies may be difficult to distinguish by appearance alone. Laboratories can use molecular probes, nucleic-acid sequencing, and MALDI-TOF for identification. Converting a mold culture into the yeast form is possible but difficult and time-consuming, so it is generally unnecessary.

Organism and distribution

The main cause of histoplasmosis discussed is Histoplasma capsulatum var. capsulatum. An African variety, var. duboisii, is also mentioned.

In the United States, the fungus is associated especially with the Mississippi, Ohio, and Missouri River valleys. Missouri, Kentucky, Arkansas, Tennessee, Ohio, Illinois, and Indiana are cited as high-prevalence states. The organism is also found in many countries worldwide.

Histoplasma occurs in soil enriched by bird droppings, including around bird roosts and chicken coops. It is also found in places where bats roost, such as caves and old trees.

Exposure and infection

Infection generally follows inhalation of airborne fungal material. Activities that can disturb contaminated soil or droppings include:

• Cleaning old barns or chicken houses
• Handling manure used as fertilizer
• Raking beneath roosting trees
• Cutting down trees inhabited by bats
• Excavating contaminated soil
• Exploring caves

Roberts describes an outbreak in which children raking beneath a tree at a school stirred up material near the building’s air intake, exposing the school community.

In the environment, Histoplasma produces several types of structures. Large, rough-walled macroconidia are useful for recognizing the fungus in culture, but are too large to reach the lung alveoli. Small microconidia and fragments of hyphae are described as likely infectious particles.

After inhalation, particles reach the lungs and are engulfed by macrophages. The fungus converts to yeast within the macrophages and can then spread through the lymphatics to chest lymph nodes and into the bloodstream, including to organs such as the liver and spleen.

Disease and host response

The body may form granulomas that contain the fungus. In a healthy person, infection may remain inactive even though the organism can persist. Later immune weakening, such as from aging or corticosteroid treatment, may allow the organism to reactivate.

Disease is especially associated with immunocompromised people or exposure to a large inoculum. An infected person may also have no active illness.

Specimens and direct examination

Respiratory specimens, including sputum and bronchoscopic samples, are important because the lungs are commonly involved. The organism may also be recovered from blood and bone marrow; bone marrow is emphasized as a useful source. Other possible sources include spinal fluid, brain, liver, spleen, biopsies, and lesions of mucous membranes.

Direct microscopic examination is not very reliable for detecting Histoplasma. Small yeasts from other organisms, including Candida glabrata, can resemble it. When seen in suitable specimens, the yeast cells are typically about 2–5 microns, often have a single bud, and may be inside mononuclear cells.

The cells can be difficult to see on routine H&E tissue sections, while methenamine silver staining highlights them more clearly. The apparent capsule around the yeast in some images is described as a staining artifact, not a true capsule. The historical name capsulatum reflects an earlier interpretation.

Culture appearance

Histoplasma produces delicate, septate hyphae and two main types of spores:

• Macroconidia: Large, rough-walled, tuberculate spores formed on short lateral hyphae. Their projections may become more prominent as the culture ages.
• Microconidia: Smaller, usually round-to-pear-shaped spores that can resemble those of Blastomyces.

Some isolates sporulate poorly or not at all, making identification by traditional microscopic morphology difficult.

Colony appearance varies substantially. Colonies may be white, tan, brown, gray, fluffy, powdery, wrinkled, or nearly ground-glass in appearance. Some isolates may produce both white and brown colony types.

Cultures may be mixed with bacteria or other yeasts, and heavy growth can occur. The lecture cautions against dismissing or handling the organism casually, noting that severe infection can be fatal.

Speakers and sources

• Sarah — Introduces the presentation; surname not provided in the subtitles.
• Dr. Glenn D. Roberts — Presenter, identified as a professor and consultant at Mayo Clinic.
• Mayo Medical Laboratories Hot Topics — Presentation series and institutional source.