Clinical Information

Histoplasma

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.

Blastomyces

Blastomyces dermatitidis is endemic throughout the Midwestern, south central, and Southeastern United States, particularly in regions around the Ohio and Mississippi river valleys, the Great Lakes, and the Saint Lawrence River. It is also found in regions of Canada. Blastomyces species are dimorphic fungi, preferring moist soil and decomposing organic matter, which produces fungal spores that are released and inhaled by humans. At body temperature, spores mature into yeast, which may remain in the lungs or disseminate through the bloodstream to other parts of the body. Through phylogenetic analysis, B. dermatitidis has been separated into 2 distinct species: B dermatitidis and Blastomyces gilchristii, both able to cause blastomycosis. B dermatitidis infections are frequently associated with dissemination, particularly in older patients, smokers, and immunocompromised hosts, while B gilchristii has primarily been associated with pulmonary and constitutional symptoms. Additional species of Blastomyces have recently been discovered and characterized, however the performance characteristics of this assay for these species are unknown.

Approximately half of patients infected with Blastomyces will develop symptoms, which are frequently nonspecific, including fever, cough, night sweats, myalgia or arthralgia, weight loss, dyspnea, chest pain, and fatigue. Symptoms may appear anywhere from 3 weeks to 3 months following infection. Diagnosis of blastomycosis relies on a combination of assays, including culture and molecular testing performed on appropriate specimens, and serologic evaluation for both antibodies to and antigen released from Blastomyces. Although culture remains the gold standard method and is highly specific, the organism can take several days to weeks to grow and sensitivity is diminished in cases of acute or localized disease. Similarly, molecular testing offers high specificity and a rapid turnaround time, however sensitivity is imperfect. Detection of an antibody response to Blastomyces offers high specificity, however results may be falsely negative in patients who are acutely ill or are immunosuppressed.