Detection of (1,3)-β-d-Glucan in Cerebrospinal Fluid in Histoplasma Meningitis

BACKGROUND: Central nervous system (CNS) histoplasmosis is a life-threatening condition, and represents a diagnostic and therapeutic challenge. Although CSF (1,3)-β-d-glucan (CSF BDG) is available as a biologic marker for diagnosis of fungal meningitis, there are limited data on its use for diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection using the Fungitell assay in patients with CNS histoplasmosis and controls. METHODS: Patients were classified as cases if there was CNS inflammation (CSF WBC ≥ 5 mm(3)/ml) plus laboratory confirmation of H. capsulatumin CNS samples or from extra-CNS sites with no alternative etiology for CSF pleocytosis. Controls were patients with histoplasmosis but no evidence of CNS involvement, an alternative diagnosis, or other fungal meningitis. RESULTS: In total, 47 cases and 153 controls were evaluated (Table 1). Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. CSF BDG was positive in 25 (53.2%) cases using a level of ≥80 pg/ml, the median CSF BDG level was 140.5 pg/ml (range from <31 to 500 pg/ml). The detection of CSF BDG level ≥80 pg/ml was not associated with positive CSF Histoplasma antigen (P = 0.28) or positive CSF Histoplasma culture (P = 0.56). The sensitivity for detection of CSF BDG was 53.2% and the specificity was 87.3%, compared with 78.7% (P = 0.009) and 96.4% (P = 0.003), respectively, for detection of antigen. CSF BDG was positive in 20 of 153 (13.1%) patients in the control group. Seven of 11 (63.6%) other CNS fungal meningitis cases (five Cryptococcus, two Aspergillus, two Blastomyces, one Candida, and one suspected fungal meningitis) had CSF BDG ≥80 pg/ml. CONCLUSION: A positive CSF BDG supports the diagnosis of fungal meningitis but cannot distinguish among the different etiologies. The sensitivity and specificity of detection of CSF BDG was lower than that of antigen detection. DISCLOSURES: L. J. Wheat, MiraVista: President and owner, equity and Salary