Introduction: Histoplasma capsulatum is one of the more common causes of infection in the midwestern and southeastern United States. Histoplasmosis, acquired by inhalation of mycelial fragments and microconidia, has become an increasingly frequent opportunistic infection among patients whose immune system is impaired either by pharmaceutical agents or by infection with human immunodeficiency virus (HIV). This accelerating trend is unlikely to decrease because the reservoir of infection, the soil, will never disappear.

The organism: Histoplasmosis is caused by the dimorphic fungus, Histoplasma capsulatum. The fungus is distributed worldwide but endemic in certain areas of North and South America. In the United States, infection has been noted primarily in the Mississippi and Ohio river valleys, where the mycelial form can be found readily in the environment, and is particularly associated with bird roosts, chicken coops, and caves.The organism is also endemic in Puerto Rico and other Caribbean islands as well as Central America; thus, infection is often seen in Latin American HIV-infected patients.

Mycology: The organism has two forms, the mycelial phase and the yeast phase. The former is present at ambient temperature and the latter at 37°C or higher. The saprobic or mycelial phase can be divided into two colony types, brown (B) and albino (A). Type A organisms grow more rapidly in culture and lose the ability to produce spores after prolonged subculturing. Type B organisms generate a brown pigment. Yeast cells from the B type are more virulent than those from the A type. The basic elements of the nutritional needs of the organism are poorly defined because of lack of a standardized medium. The organism requires vitamins, thiamine, biotin, and iron. Sulfhydryl groups in the form of cysteine or cystine are necessary for growth and maintenance of the yeast phase. Microscopic evaluation of the mycelial phase reveals two types of conidia. Macroconidia are large, ovoid bodies 8 to 15mum in diameter. The surface is decorated with slender protrusions that are referred to as tuberculate. Microconidia are small, smooth oval bodies whose diameter ranges from 2 to 5mum. These forms are believed to be the infective phase because their size is small enough to lodge in the terminal bronchioles and alveoli. The transition from the saprobic to the yeast phase is a critical step in infectivity of the fungus. At 37°C, the organism undergoes genetic, biochemical, and physical alterations that result in the production of yeast cells that are uninucleate. These forms are small, typically 2 to 5mum in diameter, and reproduce by multipolar budding. The stimulus for the transition is heat and right metabolic milieu and the shift in temperature may be sensed by a change in the fluidity of the yeast membrane.

Diagnosis: Histoplasmosis can be established with assurance only by isolation of H. capsulatum from body fluids or tissues. The typical medium that is used to recover the fungus includes brain-heart infusion agar with a source of blood plus antibiotics and cycloheximide. The latter are included to inhibit the growth of saprophytic fungi and bacteria. Cultures are incubated for up to 6 weeks. Often, growth is noted within 3 weeks, and more than 90% of cultures exhibit fungus within 7 days. All mycelial isolates are confirmed using a DNA probe that recognizes ribosomal DNA. One of the major advances in the diagnosis of histoplasmosis has been the development and introduction of an antigen detection assay that identifies a polysaccharide antigen in either urine or serum. Also available for diagnosis since the late 1940s is serology. Complement-fixing (CF) antibodies and precipitin bands have been most commonly used in the clinical laboratory. Histochemical Identification of Histoplasma capsulatum is also useful.Stains for the presence of H. capsulatum can be extremely useful in rapid identification of the fungus in various tissues or body fluids. The yeast is visualized poorly by hematoxylin-eosin staining, but it is more apparent using the periodic acid-Schiff stain. The most useful stain is either the Gomori methenamine or Grocott silver stain.The histoplasmin skin test has been used for several decades to determine who has been exposed to H. capsulatum.

Clinical presentation: The clinical presentation varies, depending on the inoculum size, the host immune status, and presence of underlying lung disease. Overt symptoms occur in 5% of individuals following low-level exposure. In 80% of cases, the symptoms are nonspecific and include fever, chills, myalgias, and nonproductive cough and chest pain. This acute syndrome can range from mild (lasting 1-5 d) to severe (lasting 10-21 d, with associated weight loss, fatigue, and night sweats). Fatigue may persist for weeks after the resolution of acute symptoms. There are a variety of acute and chronic presentations including acute asymptomatic pulmonary (lung) histoplasmosis, acute symptomatic pulmonary histoplasmosis, chronic pulmonary histoplasmosis, and disseminated histoplasmosis.