Program Schedule

Detection of High CSF Levels of (1→3)-Beta-D-Glucan in Cryptococcal Meningitis

Session: Poster Abstract Session: Fungal Infections
Saturday, October 11, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
  • Rhein_BDG_IDSA 2014 Poster.pdf (505.8 kB)
  • Background: (1-3)-β-D-glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections. However, BDG is not thought to be useful in diagnosing cryptococcosis. We evaluated the utility of cerebrospinal fluid (CSF) and serum BDG as an adjunct diagnostic tool for HIV-infected cryptococcal meningitis patients.

    Methods: BDG concentrations were measured on cryopreserved CSF (n=177) and serum (n=109) of HIV-infected patients with suspected meningitis in Uganda and South Africa using the Fungitell® assay. Correlations between BDG concentrations and quantitative CSF cryptococcal cultures, CSF cryptococcal antigen (CRAG) titers, and 18 different CSF cytokine concentrations were assessed using non-parametric tests. Mixed models evaluated longitudinal changes in CSF BDG concentrations. Survival analyses evaluated BDG’s relationship with mortality.

    Results: The Fungitell® BDG assay provided 90% sensitivity (69/77) and 85% specificity (34/40) in CSF when compared to cryptococcal meningitis diagnosed by CSF culture or cryptococcal antigen at diagnosis (n=117, 66% with Cryptococcus neoformans). Sensitivity in CSF improved to 98% (57/58) when initial fungal burdens were ≥10,000 CFU/mL. Median (IQR) CSF BDG concentrations at diagnosis were 346 (202-597) pg/mL in cryptococcal patients and 37 (20-46) pg/mL in patients without cryptococcosis. Baseline BDG concentrations correlated with CSF fungal burden (rho=0.820, P<.001) and CRAG LFA titers (rho=0.780, P<.001). BDG normalized rapidly after initiating antifungal therapy [-0.25 (95%CI: -0.31, -0.20) average change in log2BDG level per day of follow-up]. Baseline BDG concentrations correlated with MIP-1β and MCP-1 levels in CSF. Among cryptococcal meningitis patients, a BDG concentration ≥500 pg/mL was associated with increased 10-week mortality. The diagnostic performance of the BDG assay for cryptococcal meningitis was not as good in serum, where we observed 79% (37/47) sensitivity and 61% (38/62) specificity.

    Conclusion: BDG is detectable in the CSF of HIV-infected patients with Cryptococcus, and may provide useful diagnostic and prognostic information. Further research is needed to clarify the role of BDG in the immunology and management of cryptococcal disease.

    Joshua Rhein, MD1,2, Nathan Bahr, MD1, Bozena Morawski, MPH3, Charlotte Schutz4, Malcolm Finkelman, PhD5, David Meya, MMed6, Graeme Meintjes, MD4 and David Boulware, MD, MPH1,6, (1)Infectious Disease and International Medicine, University of Minnesota, Minneapolis, MN, (2)Infectious Disease Institute, Makerere University, Kampala, Uganda, (3)Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, (4)University of Cape Town, Cape Town, South Africa, (5)Associates of Cape Cod, Inc., East Falmouth, MA, (6)Center for Infectious Diseases & Microbiology Translational Research, University of Minnesota, Minneapolis, MN


    J. Rhein, None

    N. Bahr, None

    B. Morawski, None

    C. Schutz, None

    M. Finkelman, Associates of Cape Cod: Employee, Salary

    D. Meya, None

    G. Meintjes, None

    D. Boulware, None

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