Clinical Information

Histoplasma capsulatum is a dimorphic fungus endemic to the Midwestern United States, particularly along the Mississippi River and Ohio River valleys. Infection occurs following inhalation of fungal microconidia, and subsequent clinical manifestations are largely dependent on the fungal burden at the time of exposure and the patient's underlying immune status. While the vast majority (>90%) of exposed individuals will remain asymptomatic, individuals seeking medical attention can present with a diverse set of symptoms ranging from a self-limited pulmonary illness to severe, disseminated disease. Individuals at risk for severe infection include those with impaired cellular immunity, who have undergone organ transplantation, who are HIV positive, or who have a hematologic malignancy.

The available laboratory methods for the diagnosis of H capsulatum infection include fungal culture, molecular techniques, serologic testing, and antigen detection. While culture remains the gold standard diagnostic test and is highly specific, prolonged incubation is often required, and sensitivity decreases (9%-34%) in cases of acute or localized disease. Similarly, molecular methods offer high specificity but decreased sensitivity. Serologic testing likewise offers high specificity; however, results may be falsely negative in immunosuppressed patients or those who present with acute disease. Also, antibodies may persist for years following disease resolution, thereby limiting the clinical specificity.

Detection of H capsulatum antigen from urine samples has improved sensitivity (80%-95%) for the diagnosis of active histoplasmosis compared to both culture and serology. Additionally, urine antigen levels can be followed to monitor patient response to therapy, with declining levels consistent with disease resolution. Notably, however, H capsulatum antigen may persist at low levels following completion of antifungal therapy and clinical improvement.