Immunodiffusion (ID) Tests

Histoplasmosis results from infection with H. capsulatum, which has a worldwide distribution but is a particular problem in central and southeastern areas of the United States and in certain regions of Central and South America. Two precipitins can be detected in histoplasmosis patient serum directed against the “M” and “H” antigens. Antibodies against “M” antigen are the first to appear in acute pulmonary histoplasmosis and form the basis of a specific immunodiagnosis, while antibodies to “H” antigen occur later and less frequently, and their presence is often linked to extrapulmonary dissemination. Approximately 63% of culturally confirmed histoplasmosis cases have only an “M” band, whereas 90% have either an “M” band only or “H” and “M” bands in the ID test. The histoplasmosis ID and CF tests will react with about 85 – 94% of sera from patients with histoplasmosis. Antibody titers are of diagnostic and prognostic value. The parallel use of ID and CF tests and clinical data is an effective means for specific diagnosis of histoplasmosis.

Complement Fixation (CF) Tests

A positive CF test is presumptive evidence of active or recent infection with H. capsulatum. CF titers of 1:32 or greater or rising titers (a fourfold or greater increase) with yeast antigens, mycelial antigens, or both are strong presumptive evidence of histoplasmosis. Titers of 1:8 or 1:16, with either antigen, are generally considered suggestive of histoplasmosis but are less readily interpreted. Failure to demonstrate CF antibodies does not exclude histoplasmosis, especially if only a single specimen is tested.

In primary pulmonary infection, CF titers to the yeast antigen occur within 10 to 21 days following exposure to the organism, usually by the time symptoms are present. CF titers with the mycelial antigen are generally lower and develop later than the yeast antigen titers. However, in certain chronic cases, the mycelial antigen titers may be higher or be the only antigen positive.

In general, higher titers are associated with more severe disease and increasing titers (fourfold or greater rise) on serial specimens indicates progression of disease. However, persistent low titers may also indicate severe disease (up to 15% of chronic pulmonary cases have low or negative titers). Following successful therapy, the CF titers will slowly return to negative, usually within 3 months; however, rare patients have had persistent titers for up to 6 months following successful therapy.

Sera from patients with other mycoses may cross-react with Histoplasma antigens in the CF test, most notably blastomycosis and rarely, coccidioidomycosis patients. For more complete serologic testing, immunodiffusion and latex agglutination tests should be performed in parallel with the CF tests.

Latex Agglutination (LA) Tests for Histoplasmosis

A positive LA test result can be demonstrated as early as 2 to 3 weeks after infection with H. capsulatum; therefore the LA test is an excellent presumptive test that aids in the diagnosis of acute histoplasmosis. The LA test has sensitivity of 100% and 46% for acute primary pulmonary and chronic pulmonary infections, respectively, and an overall sensitivity of 62%. The specificity of the LA test is 97%.

However, cross reactions with other systemic mycoses may occur with the LA test. Results should be interpreted with caution, particularly if only one specimen has been examined and the titer is low. The test should be repeated after 1 to 3 months. Additionally, confirmation of the LA test result by ID and/or CF is recommended. False negative reactions may occur in immunocompromised or immunosuppressed patients or persons with chronic histoplasmosis. Agglutinating antibodies to H.capsulatum antigens may be significantly increased in histoplasmin skin testing.

Immunodiffusion Plates

Analyte Specific Reagents (ASR) and Research-Use Only (RUO) Products for Histoplasma Antigens and Antibodies

HAG102

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Immunodiffusion (ID)

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Complement Fixation (CF)

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Latex Agglutination (LA)

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