Blastomycosis is a systemic fungal infection caused by inhaling the spores of the dimorphic fungi, primarily Blastomyces dermatitidis and Blastomyces gilchristii. This infection is concentrated in specific geographic regions, most notably the Ohio and Mississippi River valleys, and the Great Lakes areas of North America. Diagnosing blastomycosis is challenging because its symptoms frequently imitate other common illnesses, often presenting as a pneumonia that can be mistaken for a bacterial infection, tuberculosis, or even lung cancer. Because the clinical presentation is so varied and nonspecific, accurate laboratory testing is required to confirm the presence of the fungus and ensure patients receive the correct antifungal treatment quickly.
Direct Microscopic Examination and Culture
The definitive method for diagnosing blastomycosis has long been the fungal culture, which involves growing the organism from a clinical sample. Samples such as sputum, bronchoalveolar lavage fluid, or tissue biopsies are placed on specialized media to allow the fungus to propagate. The major limitation of this method is the slow turnaround time, as it can take up to two to four weeks for the Blastomyces mold form to grow enough for a conclusive identification.
Laboratories must handle these cultures under strict biosafety conditions because the mold form of the fungus can release infectious spores into the air. Before waiting for culture results, a rapid presumptive diagnosis can often be made through direct microscopic examination of the clinical specimen. This involves inspecting the sample for the characteristic morphology of the yeast, specifically looking for large, thick-walled yeast cells exhibiting a single broad-based bud.
Antigen Detection Assays
Antigen detection assays have become the preferred initial screening method because they offer a rapid diagnosis, often within hours, which is critical for timely treatment. These tests work by detecting a specific component of the fungal cell wall, a polysaccharide called galactomannan, which the fungus releases into the bloodstream and is concentrated in the urine. Testing urine is generally preferred over serum due to the higher concentration of the antigen in the urinary tract, resulting in greater test sensitivity.
However, a significant limitation of the antigen assay is its potential for cross-reactivity with other endemic fungi. The galactomannan antigen of Blastomyces is structurally similar to the antigen released by Histoplasma capsulatum, the fungus that causes histoplasmosis. Consequently, a patient with histoplasmosis will frequently yield a positive result on the blastomycosis antigen test, necessitating further confirmatory testing.
The Role of Serology and Molecular Tests
Serology, or antibody testing, provides another layer of diagnostic information by detecting the body’s immune response to the Blastomyces infection. These assays measure the presence of antibodies that the immune system produces to fight the invading fungus. Serology tests are generally less reliable for an acute diagnosis because it can take several weeks for the body to mount a detectable antibody response, especially in patients with weakened immune systems. Antibody tests may also have lower sensitivity and specificity compared to antigen detection, and a negative result does not definitively rule out an active infection.
Molecular tests, most commonly Polymerase Chain Reaction (PCR), offer a highly specific method to detect the fungus’s DNA directly from the patient’s sample. PCR is especially useful because it can distinguish between Blastomyces and other fungi and can even differentiate between B. dermatitidis and B. gilchristii. While highly accurate and fast, molecular tests are often reserved for specialized reference laboratories or for use in cases where other tests are inconclusive.
Understanding the Diagnostic Algorithm
In clinical practice, no single test is used in isolation; instead, clinicians employ a strategic algorithm to arrive at a confident diagnosis. When blastomycosis is suspected, the initial step is often a rapid antigen detection assay in urine due to its high sensitivity and speed. A positive antigen result provides immediate support for starting presumptive antifungal therapy, but this result is then tempered by the possibility of cross-reactivity with other fungi. To confirm the diagnosis and overcome the antigen test’s lack of specificity, clinicians will concurrently send samples for the slower, but definitive, fungal culture or for highly specific molecular PCR testing. The final diagnosis hinges on correlating all laboratory results—antigen, culture, and potentially serology—with the patient’s specific symptoms, their exposure history in endemic areas, and findings from chest imaging.