Histoplasma capsulatum is a fungal organism which causes histoplasmosis and is found in
the United States, most commonly in states along the Ohio and Mississippi river valleys.
The organism itself is found in the soil but is also associated with or found in areas
with large amounts of bird or bat droppings, for example in caves.
Infection with Histoplasma occurs most commonly by inhalation of the tiny Histoplasma microconidia
or spores that are released following disruption of soil.
Following exposure, most otherwise healthy individuals will remain asymptomatic without
any manifestations of infection.
However, those individuals that do develop signs of infection often present with flu-like
and respiratory symptoms including for example fever, headache, chills, a cough and fatigue.
More severe forms of the disease, including for example dissemination of the organism
into the blood stream or other organ systems, occurs more commonly in immunosuppressed patients
and in those with hematologic malignancies.
So it’s important to be able to quickly and accurately make the diagnosis of a Histoplasma
infection in order to promptly start effective antifungal treatment.
There are a number of different methods by which infection with Histoplasma can be identified
in the laboratory, including isolation of the organism in culture, detection of Histoplasma
DNA by nucleic acid amplification testing, identification of the organism by histopathology
from a biopsy specimen, detection of antibodies to Histoplasma in blood and finally, detection
of Histoplasma antigen in urine.
While these methods are all valid and can and in certain cases should be pursued, detection
of Histoplasma antigen is among the most rapid methods available and can be performed on
urine, which is a readily accessible specimen source.
The Histoplasma antigen test is a standard enzyme immunoassay or EIA designed to detect
a specific antigen or molecule released from growing Histoplasma organisms and we have
validated the performance of this test on urine specimens.
The Histoplasma urine antigen test used at Mayo Medical Laboratories is a laboratory
developed test which has been significantly modified from previously published evaluations
of this assay in order to improve the clinical sensitivity and specificity of the test for
detection of histoplasmosis.
The Histoplasma Urine Antigen assay will provide both a qualitative and a quantitative result.
Qualitative results can be either positive, negative or indeterminate and quantitative
antigen values will be reported in nanograms/mL.
Importantly, samples that are resulted as indeterminate, which is expected to occur
in less than 8% of cases, will automatically reflex for confirmatory testing by a different
Histoplasma urine antigen test.
This test can be used to both establish an initial diagnosis of Histoplasma infection
and to monitor a patient’s response to antifungal therapy.
In patients who have not been previously diagnosed with histoplasmosis, a positive result by
the Histoplasma Urine Antigen test is significant, indicating infection with Histoplasma and
patients should be managed according to established guidelines.
It is important to know however, that patients who are infected with Blastomyces dermatitidis,
which is another fungal organism also found throughout the MidWest United States, these
patients may also be positive by this assay.
This cross-reactivity is a known limitation of all Histoplasma Urine Antigen detection
assays that are currently available for clinical testing and it is therefore important to monitor
other laboratory results, including culture and serology, to confirm the infectious agent.
Patients who are negative by the Histoplasma Urine Antigen assay can be presumed to not
be infected by Histoplasma.
However, if the infection is localized and very recent, the urine antigen test may initially
be negative.
Therefore, if suspicion for histoplasmosis continues, it is recommended to submit a second,
new urine sample and in the meantime, to monitor other laboratory results like culture and
serologic testing.
For patients who are on antifungal treatment, serial testing for Histoplasma urine antigen
levels can be helpful to monitor disease progression.
In general, falling or decreasing urine antigen levels have been associated with disease resolution
whereas, increasing antigen levels are concerning for treatment failure.