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Chapter: Microbiology and Immunology: Mycology, Fungi: Systemic Mycoses


Histoplasmosis is primarily a disease of reticuloendothelial sys-tem caused by an intracellular fungus Histoplasma capsulatum. H. capsulatum is a dimorphic fungus, which occurs in twostages: as a mold in soil and as yeast at body temperature in mammals.


Histoplasmosis is primarily a disease of reticuloendothelial sys-tem caused by an intracellular fungus Histoplasma capsulatumH. capsulatum is a dimorphic fungus, which occurs in twostages: as a mold in soil and as yeast at body temperature in mammals. On SDA medium at 37°C, this fungus produces cottony mycelial growth. The colony is characterized by thin, branching, septate hyphae that produce tuberculate macroco-nidia and microconidia. The macroconidia are thick-walled, spherical spores measuring 8–20 mm in diameter and have fin-ger-like projections. These are diagnostic form of the fungus. The microconidia are smaller and thin-walled spores, and are the infectious form of the fungus.

The parasitic or tissue phase of the fungus is a yeast that measures 2–4 mm in diameter. It is exclusively found within macrophages in the infected host.

H. capsulatum infection is acquired by inhalation of conidiaand mycelial fragments from contaminated soil. Once inhaled, it is deposited in alveoli of the lung and transformation from the mycelial to the pathogenic yeast form occurs intracellularly inside the macrophages. The yeast inside the macrophages mul-tiplies in approximately 15–18 hours. Multiplication continues within the phagosomes despite fusion with lysosomes. This is possibly due to production of certain proteins by yeasts that inhibit the activity of lysosomal proteases.

CMI is key component of host defense against the fungus. T lymphocytes are crucial in limiting the extent of infection. In persons with impaired CMI, Histoplasma species which remained latent in healed granulomas may be reactivated, resulting in histoplasmosis.

Most infected individuals are asymptomatic. Nevertheless, H. capsulatum causes acute pulmonary histoplasmosis, chronicpulmonary histoplasmosis, and progressive disseminated his-toplasmosis. Majority of patients with acute pulmonary histo-plasmosis are asymptomatic. Incubation period varies from 3 to 14 days. Fever, headache, malaise, myalgia, abdominal pain, and chills are common symptoms. Cough, hemoptysis, dys-pnea, and/or chest pain may be present. Chronic pulmonary histoplasmosis is seen in patients with underlying pulmonary disease. Cough, weight loss, fevers, and malaise are symptoms.

Progressive disseminated histoplasmosis is seen in patients who are immunocompromised, such as patients with AIDS.

H. capsulatum is predominantly found in river valleys inNorth and Central America. It is endemic in the Ohio, Missouri, and Mississippi River valleys of the United States.

In endemic areas, the soil provides an acidic, damp environment with high organic content, which favors the growth of fungal mycelia. Bats play an important role in trans-mission of the disease. They can become infected, and they transmit the fungus through their droppings. The soil contam-inated with birds’ excretions and droppings of bats remains highly infectious for years. Moreover, human infection occurs following inhalation of spores from contaminated soil.

Laboratory diagnosis depends on demonstration of oval yeast cells within macrophages in bone marrow aspirates and in tissue biopsy specimens. Biopsy of oropharyngeal ulcers is usually diagnostic. Culture of sputum and blood on SDA at 25°C shows hyphae with tuberculoid macroconidia and at 37°C shows yeasts. Sputum culture is pos-itive in approximately 10–15% patients with acute pulmonary histoplasmosis and in 60% of patients with chronic pulmonary histoplasmosis. Complement-fixation test (CFT) and immuno-diffusion (ID) are useful serological tests for demonstration of specific antibodies in serum. The CFT titer greater than 1:8 is considered positive. A titer of 1:32 or more suggests active his-toplasmosis. Cross-reactivity with antigens from B. dermatitidis andC. immitis is a noted problem that may give rise to a false-positive reaction. The ID test detects antibodies to two gly-coproteins, H and M, of H. capsulatum. Anti-H antibody is more specific for active histoplasmosis, is positive in 50–80% of patients, and remains elevated for years.

Amphotericin B is the drug of choice for treatment of disseminated disease. Fluconazole is often recommended for meningitis due to its better penetration of the cerebrospinal fluid (CSF). Asymptomatic or mild condition needs no treatment.

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