What is Histoplasma?

Definition

Histoplasma is a genus of fungi
containing a single species that is the causative agent of the disease
histoplasmosis.

Natural Habitat and Features

The species H. capsulatum includes two varieties, H.
capsulatum var. capsulatum and H.
capsulatum var. duboisii. H. c. var.
capsulatum is a New World variety that causes histoplasmosis
involving primarily the pulmonary and reticuloendothelial systems, whereas
H. c. var. duboisii, the cause of African
histoplasmosis, usually involves infections of the bones and skin.

Histoplasma is a naturally occurring fungus that is generally
found in soil contaminated with either bird or bat droppings. It is endemic to the Ohio, Tennessee, Missouri, and
Mississippi river basins of the United States. The fungus is also found in
tropical areas of Central America, South America, eastern Asia, Australia, and
eastern and central Africa, often in caves that contain bat guano (feces).

Histoplasma is a thermally dimorphic fungus, which means that it
has two morphs, or forms, depending upon the temperature at which it grows. At
temperatures of approximately 77° Fahrenheit (25° Celsius), an average soil
temperature, it grows in mold form. Colonies at this temperature grow slowly and
have a granular to cottony texture and a whitish color that turns buff brown as
the fungus ages. Once within a human host, growing at normal body temperature of
98.6° F (37° C), ovoid, cream-colored budding yeast cells are formed. While within
soil, the hyphae, or fungal strands, are septate and hyaline. Conidiophores, the
spore-bearing portions of the fungus, grow at right angles to the parent colony,
and both macroconida and microconidia are present. The macroconidia are
unicellular, large, tuberculate, thick-walled structures. These macroconidia are
also called tuberculochlamydospores or macroaleurioconidia.
Histoplasma microconidia are unicellular and round and possess
either rough or smooth walls.

Histoplasma grows best in moist, acidic soil conditions such as those found in caves, poultry houses, and silos serving as bird roosts. The fungus can contaminate soil for years and spores can be inhaled when the soil is disturbed.

Pathogenicity and Clinical Significance

When spores of H. capsulatum from contaminated soil are inhaled, they lodge in the lungs. In the alveoli of the lungs, macrophages of the immune system attack the fungal spores and transport them to the lymph nodes of the chest. Inflammation, scarring, and calcification can then occur in the lungs. The majority of people who contract histoplasmosis, however, have no symptoms, but for some, an acute pulmonary phase of the disease occurs. Symptoms of acute pulmonary symptomatic histoplasmosis infection start within three to seventeen days of initial exposure. This phase is characterized by cold or flulike symptoms and may last two weeks or longer. Fever, periodic sweats, muscle aches, a dry cough, chest pain, and loss of appetite often occur.

Rare but serious complications of acute phase infection include enlargement of
the lymph nodes of the chest, causing esophageal or airway obstruction and making
swallowing and breathing extremely difficult. Fibrosing mediastinitis, severe scarring of the lymph nodes in the chest,
may also cause chest pain and breathlessness and can be life-threatening.
Pericarditis (inflammation of the pericardial sac around the
heart), meningitis (inflammation of the meninges and
cerebrospinal
fluid of the brain and spinal cord), and arthritis are
all severe complications of acute histoplasmosis cases. Adrenal insufficiency may
also occur if adrenal glands are destroyed by the fungus.

Chronic pulmonary cases of histoplasmosis symptomatically mimic
tuberculosis. These cases usually occur in patients who
already have a lung disease, such as emphysema. Disseminated or systemic
cases of histoplasmosis affect multiple organ systems and can prove fatal to
elderly or immunocompromised persons. Liver and spleen enlargement, Addison’s
disease, meningitis, pericarditis, and pneumonia may all result from disseminated
histoplasmosis.

Ocular histoplasmosis damages the retina, resulting in scar tissue that can lead to leakage and subsequent vision loss. In cases of African histoplasmosis, skin lesions and osteolytic lesions, particularly in the skull, ribs, and vertebrae, frequently develop. Also common is fever and lymph node enlargement.

Fungal samples from sputum, blood, and infected organs can be cultured in the
laboratory for definitive diagnosis of histoplasmosis. However, this process may
take as long as four weeks, so it is not the diagnostic tool of choice for
suspected cases of disseminated histoplasmosis. Blood samples may reveal antigens
or antibodies against Histoplasma; antigens
may also be present in the urine of infected persons. If a person has been
infected in the past with Histoplasma, blood tests can give
false-positive results, which may mask a different type of infection.

Fungal stain tests can be conducted on tissue samples, but because other fungi resemble H. capsulatum, a misdiagnosis is possible with this technique. Chest X rays, computed tomography (CT) scans, and bronchoscopies may also be useful in assisting with a definitive diagnosis.

Drug Susceptibility

Treatment with amphotericin B for one to two weeks is standard for severe cases of acute pulmonary symptomatic histoplasmosis. Steroid treatment with drugs such as methylprednisone may follow amphotericin B once patients are stabilized. Treatment with itraconazole may continue for one year following serious cases. Other antifungal drugs such as fluconazole and ketoconazole may occasionally be used.

For chronic pulmonary histoplasmosis cases that involve cavitary lesions within the lungs, treatment includes long-term itraconazole use and surgical intervention. Ocular histoplasmosis treatment requires steroids. Antifungal treatment is of little use for the rare, severe complications of pericarditis and fibrosing mediastinitis.

Bibliography

Hage, C. A., et al. “Histoplasmosis.” In Harrison’s Principles of Internal Medicine, edited by Joan Butterton. 17th ed. New York: McGraw-Hill, 2008.

Hospenthal, D. R., and H. J. Becker. “Update on Therapy for Histoplasmosis.” Infectious Medicine 26 (2009): 121-124. Discusses the current drug and surgery protocols for various types of histoplasmosis.

Kauffman, C. A. “Histoplasmosis: A Clinical and Laboratory Update.” Clinical Microbiology Reviews 20, no. 1 (2007): 115-132. Provides a recent review of testing and treatment for histoplasmosis.

Ryan, Kenneth J., and C. George Ray, eds. Sherris Medical Microbiology: An Introduction to Infectious Diseases. 5th ed. New York: McGraw-Hill, 2010. A textbook presentation of histoplasmosis culture and diagnostic techniques.