Histoplasma capsulatum is a dimorphic fungus, which exists as a mold in the environment and as a yeast at body temperature. Histoplasmosis is a common fungal infection in the United States that causes respiratory illness. Following infection, H. capsulatum is engulfed by macrophages and disseminated by the reticuloendothelial system. Symptoms include fever, headache, and respiratory symptoms, although infected persons can remain asymptomatic. Some patients progress to pneumonia and mediastinal or hilar lymphadenopathy. Most patients will recover regardless of treatment, but severe disease can lead to respiratory failure and should be treated. Immunocompromised patients are at high risk for developing systemic histoplasmosis.

Illness usually is acquired from inhalation of soil contaminated with bird or bat droppings. Endemic areas include the midwestern states, particularly the Mississippi and Ohio River valleys.  Human-to-human transmission does not occur. 

Disseminated histoplasmosis can be detected by culture, antigen detection, and/or serology. Culture of CSF fluid yields growth of H. capsulatum in about 50% of Histoplasma meningitis cases. Detection of H. capsulatum antigen in serum or urine has the highest sensitivity for disseminated disease (92%). Serial antigen testing is helpful in monitoring response to therapy. A confirmed case of histoplasmosis is defined as a serum or urine test positive for H. capsulatum, regardless of a person's symptoms. Antigen cross-reactivity may occur with other dimorphic mycoses such as blastomycosis.

Serologic detection of antibody to H. capsulatum is less sensitive than antigen testing, especially in immunosuppressed patients. Antibody testing is of limited usefulness in endemic regions where many individuals test positive. Antibody tests can be performed on serum or cerebrospinal fluid. Both complement fixation and immunodiffusion assays are available. Complement fixation measures total antibodies against both mycelial (mold) and yeast components of H. capsulatum and has higher sensitivity but lower specificity than immunodiffusion. Detection of antibodies to both H and M antigens is consistent with active infection. Detection of antibody to only the M antigen is seen in both current and past infection. Antibody to only H antigen is seldom seen and is not diagnostically useful.

Kauffman CA. Histoplasmosis: a clinical and laboratory update. Clin Microbiol Rev 2007;20:115–32.