Fungal cell walls are primarily composed of polysaccharides such as glucan, chitin, and mannan. (1-3)-β-D-Glucan (BDG) is the major constituent of the cell walls of most pathogenic and saprophytic fungi, including Candida, Aspergillus, Fusarium, Histoplasma, and Pneumocystis. However, Zygomycetes, such as Absidia, Blastomyces,Mucor, and Rhizopus, lack BDG. Likewise, Cryptococcus produces extremely low levels of BDG.
Opportunistic fungal infections can cause serious illness in patients who are immunosuppressed, including hematopoietic stem cell and solid organ transplant recipients, and those with immune deficiencies. Fungitell is an FDA approved test that measures BDG in serum, CSF, and bronchial lavage to help diagnose invasive fungal infections. Elevated BDG levels in serum suggest the presence of an invasive fungal infection. The test detects BDG from the following pathogens: Candida spp., Acremonium, Aspergillus spp., Coccidioides immitis, Fusarium spp., Histoplasma capsulatum, Trichosporon spp., Sporothrix schenckii, Saccharomyces cerevisiae, and Pneumocystis jiroveci.
A meta-analysis of β-D-glucan cited pooled sensitivity and specificity of Fungitell for the diagnosis of an invasive fungal infection as 71% and 82%, respectively.
Serum from normal subjects contains low levels of detectable BDG (<60 pg/mL) likely due to the presence of commensal Candida species in the gastrointestinal tract. Serum BDG levels of 60-79 pg/mL are considered indeterminate, while results >80 pg/mL are indicative of a possible invasive fungal infection.
Fungitell results are best interpreted with consideration of its limitations. False-positive results have been attributed to concomitant bacterial infections (especially Streptococcus), exposure to hemodialysis cellulose membranes, and infusion of intravenous immunoglobulin or albumin. Furthermore, surgery patients exposed to glucan-containing sponges or gauze may have elevated levels for 3-4 days post-operatively.
False negative reactions are associated with lipemic specimens, hemolyzed specimens and infections with fungi that lack significant levels of BDG such as Zygomycetes (Mucor, Rhizopus, and Absidia), Cryptococcus species, and Blastomyces dermatitidis.
Serum BDG concentrations decrease within two weeks after initiation of anti-fungal therapy in patients who are responding to therapy. A continuous increase in serum BDG concentrations is seen in patients not responding to antifungal treatment. Once-weekly testing is recommended to assess response to treatment.
Specimen requirement is 3 to 5 mL of blood collected into a red top tube of blood with or without a serum separator gel. The original sample, not a pour-off tube, should be submitted to decrease the likelihood of false-positive results due to environmental contamination.
References
Karageorgopoulos DE, et al, β-d-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis. Clin Infect Dis. 2011;52(6):750–770.
Tran T, Beal SG, Application of the 1,3-B-D-Glucan (Fungitell) Assay in the Diagnosis of Invasive Fungal Infections, Arch Pathology Lab Med, 2016;140(2):181-185
Ramanan P, Wengenack NL, Theel ES. Laboratory diagnostics for fungal infections: a review of current and future diagnostic assays. Clin Chest Med. 2017;38(3):535-554
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