What is the role of antigen testing in the workup of fungal pneumonia?

Updated: Jun 21, 2019
  • Author: Romeo A Mandanas, MD, FACP; Chief Editor: Guy W Soo Hoo, MD, MPH  more...
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These provide a more rapid and sensitive test when compared with culture methodology. Various antigen detection assays, such as galactomannan enzyme immunoassay for detection of invasive aspergillosis, are now in clinical use. Polymerase chain reaction (PCR)–based assays are also available for detecting various pathogens, including Aspergillus, Histoplasma, and Candida species. [17, 18, 19]

Comparison of these assays (antigen detection using enzyme-linked immunosorbent assay [ELISA] or latex agglutination and molecular detection with PCR) show equal specificities for all 3 assays (≥97%) in the detection of Candida species. PCR-based assays are most sensitive compared with ELISA and latex agglutination (95%, 75%, and 25%, respectively).

The newest available testing in the diagnosis of blastomycosis is an enzyme immunoassay performed on urine or serum that detects a cell wall galactomannan antigen found in B dermatitidis. However, the cross reactivity with H capsulatum is close to 100%. [5] Therefore, in patients with blastomycosis, the sensitivity or specificity of these tests is not clear. [5]

For Aspergillus species antigen, galactomannan assay findings may be positive in the blood very early prior to clinical suspicion of invasive fungal infection and may be of use in monitoring and preemptive treatment in high-risk populations. [1, 20, 21, 22]

Using a galactomannan platelia Aspergillus enzyme immunoassay approved by the US Food and Drug Administration (FDA), investigators showed that two consecutive samples with an optical index of 0.5 provided the highest test accuracy (specificity, 97.5%; sensitivity, 92.1%; positive predictive value, 87.5%; negative predictive value, 98.5%). [23] Testing in bronchoalveolar lavage (BAL) fluid increased the sensitivity compared with serum galactomannan assay from 71-100%. [24] Care should be taken, however, because false-positive results have been reported in patients taking piperacillin-tazobactam antibiotics and certain intravenous fluids, such as plasmalyte. [25]

Beta-glucan testing is also available and may be comparable or more sensitive than galactomannan assays in diagnosing invasive aspergillosis and can detect a broad spectrum of invasive fungal pathogens, including Pneumocystis jirovecii. [1, 26] Several kits are available worldwide. False-positive results have also been reported in patients receiving fungal-derived antibiotics and cross-reactions have been reported with Pseudomonas aeruginosa infections. [27]

The molds causing mucormycosis, which belong to the subphylum Mucoromycotina, do not contain galactomannan or beta-glucan in their cell wall. Therefore, mucormycosis cannot be diagnosed with the galactomannan or beta-glucan assays. [1]

Aspergillus PCR is most sensitive (100%) when performed on the bronchial lavage fluid of patients with invasive pulmonary aspergillosis, but it is only 40-66% sensitive when performed on the blood. No standardized protocols have been established among laboratories performing this assay. [12, 18, 27]

ELISA or latex agglutination is 70-80% sensitive for identifying H capsulatum and C immitis. PCR for H capsulatum from the bronchoalveolar lavage fluid aids in the rapid detection within 24 hours in a patient with AIDS, and this has been confirmed 10 days later based on the growth and culture isolation of the organism from various tissues.

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