Histoplasma Antigen, Urine
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Histoplasma capsulatum is a dimorphic fungus endemic to the Midwest 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, patients who have undergone organ transplantation, are HIV positive, or have a hematologic malignancy.
The available laboratory methods for the diagnosis of Histoplasma capsulatum infection include fungal culture, molecular techniques, serologic testing, and antigen detection. Among these, 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 Histoplasma 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, Histoplasma capsulatum antigen may persist at low levels following completion of antifungal therapy and clinical improvement.
Aids in the diagnosis of Histoplasma capsulatum infection
Monitoring Histoplasma antigen titers in urine
Presence of Histoplasma antigen in urine is indicative of current or recent infection with Histoplasma capsulatum.
Declining levels of Histoplasma antigen are indicative of disease regression and can be used to monitor patient response to antifungal therapy. Notably, low-level titers may persist for extended periods of time following appropriate treatment and resolution of infection.
Urine samples with "Indeterminate" results are automatically reflexed to MiraVista Diagnostics (Indianapolis, IN) for confirmatory testing. Clinical decisions regarding Histoplasma infection should not be based on an Indeterminate result alone. Other laboratory findings, including Histoplasma serology, fungal culture, and molecular tests (eg, RT-PCR) should be considered, alongside clinical presentation and exposure history, to confirm the diagnosis.
The absence of detectable Histoplasma antigen in urine is consistent with the absence of infection. Repeat testing on a fresh urine sample if early acute Histoplasma infection is suspected.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Cross-reactivity with other fungal infections, including Blastomyces dermatitidis, may occur. Positive results should be correlated with other clinical and laboratory findings (eg, culture, serology, etc).
Low-level positive or indeterminate titers may persist following resolution of infection and completion of appropriate treatment regimen.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Histoplasma Ag Result
Histoplasma Ag Value
Negative: 0.00 - 0.10
Positive: > or =0.50
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Theel ES, Harring JA, Dababneh AlS, et al: Re-evaluation of Commercial Reagents for Detection of Histoplasma capsulatum Antigen in Urine. J Clin Micro epub 28 Jan 2015, doi: 10.1128/JCM.03175-14
2. Wheat LJ, Freifeld AG, Kleiman MB, et al: Clinical Practice Guidelines for the Management of Patients with Histoplasmosis: 2007 Update by the Infectious Diseases Society of America. Clin Infect Dis 2007;45:807-825