What is the serologic evaluation for histoplasmosis (Histoplasma capsulatum infection)?

From the Guidelines

Serologic evaluation for histoplasmosis should involve testing for antibodies against Histoplasma capsulatum, with the most useful tests being immunodiffusion and complement fixation, as recommended by the American Thoracic Society clinical practice guideline 1.

Diagnostic Approach

For suspected histoplasmosis, I recommend ordering both immunodiffusion and complement fixation tests simultaneously to maximize diagnostic yield.

• The immunodiffusion test detects H and M precipitin bands, with M bands appearing within 2-4 weeks of infection and H bands indicating active disease.
• Complement fixation measures antibody titers, with titers ≥1:32 suggesting active infection and a fourfold rise between acute and convalescent samples being diagnostic.

Antigen Detection

Antigen detection in urine or serum is particularly valuable for disseminated or acute pulmonary disease, with higher sensitivity in urine, as noted in the clinical practice guidelines for the management of patients with histoplasmosis 1.

Limitations and Considerations

False positives can occur with other fungal infections like blastomycosis.

• Serologic testing is most useful when combined with clinical presentation, exposure history, and radiographic findings.
• Negative serologic results don't exclude histoplasmosis, especially in immunocompromised patients or very early infection, and additional testing like culture or histopathology may be necessary for definitive diagnosis.

Clinical Context

The choice of diagnostic tests should be guided by the clinical context, including the severity of illness, immune status, and potential for disseminated disease, as emphasized in the guidelines 1.

From the Research

Serologic Evaluation for Histoplasmosis

• The serologic evaluation for histoplasmosis involves the detection of antibodies against Histoplasma capsulatum, which can be achieved through various immunoassays 2.
• The most commonly used techniques for antibody detection are immunodiffusion and complement fixation (CF) tests, with sensitivities ranging from 70 to 100% and specificities of 100% for immunodiffusion, and 60 to 90% for CF tests 2, 3.
• Immunodiffusion tests can detect specific antibodies to H. capsulatum, with the presence of M-band or H- and M-bands indicating a positive result 3.
• CF tests can also detect antibodies to H. capsulatum, with reactivity against both mycelial and yeast antigens 3.
• Radioimmunoassay (RIA) is another experimental serological test that is more sensitive than CF but less specific 4.
• The sensitivity and specificity of these tests can vary depending on the clinical form of histoplasmosis, with chronic cavitary histoplasmosis, progressive disseminated histoplasmosis, and acute pulmonary histoplasmosis having different serologic profiles 4.

Comparison of Serologic Tests

• Studies have compared the immunodiffusion and complement fixation tests in the diagnosis of histoplasmosis, with results showing that immunodiffusion tests are more specific and sensitive than CF tests 5.
• The use of histoplasmin or yeast antigen in CF tests can also affect the sensitivity and specificity of the results, with yeast antigen being more sensitive than histoplasmin 5.
• The significance of serum antibodies to H. capsulatum in endemic areas has also been evaluated, with results showing that low-level antibody titers can be found in healthy individuals, but high-level titers or precipitin bands are rare in persons who live in endemic areas 6.

Clinical Applications

• Serologic testing remains a valuable asset to support the diagnosis of histoplasmosis, particularly when direct detection methods fail to identify an infection 3.
• The choice of serologic test and interpretation of results should be based on the clinical context and the specific characteristics of the test, including sensitivity, specificity, and ease of performance 2, 3, 5.