Fungal Infections

Beta 1,3-D-glucan detection

Detection of 1,3-β-D-glucan (glucan) in serum is useful in the diagnosis of Pneumocystis jirovecii pneumonia and some invasive fungal infections. Glucan is a fungal cell wall component circulating in the blood of patients and is detected using assays which detect activation of factor G of the coagulation cascade of the remarkably ancient horseshoe crabs. [They have evolved very little over the last 450 million years.]

Glucan assay kits are available from 7 companies: Fungitec G-Test MK (Seikagaku) and Fungitell (Associates of Cape Cod), both kinetic colourimetric assays, the kinetic turbidimetric β-Glucan Test Wako (Wako Pure Chemical Industries), the MB-80Set microbial dynamic detection system (manufactured by Beijing Gold Mountainriver Tech), the endopoint chromogenic B-G Star kit (Maruha), the Dynamiker Fungus (1-3)--β-D-glucan Assay (by Dynamiker) and the Goldstream Fungus (1-3)--β-D-glucan Test (by Era Biology). The assay platforms differ for the tests. As glucan is present in large quantities in almost all environments, manufacture of glucan kits is difficult and stringent precautions must be taken in the laboratory to minimize external contamination. The dynamic range and positive cut-offs differ between kits.

Some fungi produce very little or no 1,3-β-D-glucan, notably Cryptococcus spp. and most of the Mucorales, and so these infections will not be detected with glucan measurementCandida parapsilosis candidaemia may have lower 1,3-β-D-glucan levels than expected (article). Glucan is detectable in the CSF of patients with coccioidoidal meningitis. Some extraneous materials will produce false positive assays, including cotton or rayon surgical swabs (persisting for a few days after surgery), blood transfusion, albumin and immunoglobulin infusions and haemodialysis.

In the diagnosis of Pneumocystis pneumonia, a recent meta-analysis indicated a diagnostic sensitivity and specificity of 96% and 84%, with a diagnostic odds ratio of 102. For invasive fungal infections in many different patient populations, the sensitivity and specificity were 80% and 82% with a diagnostic odds ratio of 26. For candidaemia, the Fungitell assay has a sensitivity of 87% and the Wako single sample assay (newly launched) has as lower sensitivity of 43%, with both assays having an very high negative predictive value of >99%.

There is also uncertainty about the sensitivity in terms of an early diagnosis, especially for invasive aspergillosis during profound neutropenia. Glucan levels do decline on antifungal treatment, but do so erratically and slowly cannot be used to assess response to therapy. 

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