Cerebrospinal Fluid (1,3)-Beta-d-Glucan Testing Is Useful in Diagnosis of Coccidioidal Meningitis

Diagnosing coccidioidal meningitis (CM) can be problematic owing to its infrequency and/or a delay in the positivity of a cerebrospinal fluid (CSF) culture or CSF antibody, particularly if the primary coccidioidal infection is unrecognized. We tested 37 CSF specimens, 26 from patients with confirmed CM and 11 from patients with suspected microbial meningitis without fungal diagnosis, for (1,3)-beta-glucan (BG). BG in CM CSF specimens ranged from 18 to 3,300 pg/ml and in controls ranged from <3.9 to 103 pg/ml. Diagnostic performance was determined using a 31-pg/ml cutoff (the bottom of the serum range according to the directions for the commercial kit, although further serial dilutions of the standard indicated linearity to 3.9). Sensitivity was 96%, specificity was 82%, positive and negative predictive values were 93% and 90%, and the area under the receiver operating characteristic curve was 0.937. Fifteen of 15 samples of >103 pg/ml were CM. The one false-negative specimen was from a patient with a pseudosyrinx, without inflammatory evidence of meningitis activity. Serial samples from some patients were positive at ≤8 years, indicating no loss of positivity with chronicity. Samples stored frozen since 2000 included those with 2 of the 3 highest values, indicating that fresh samples not required. A previous study indicated serum sensitivities of 53% in acute, 50% in resolved, and 83% in disseminated and meningeal coccidioidomycosis. Three studies of other fungal meningitides ranged from 86 to 1,524 pg/ml CSF, with 37 controls of <4 to 115 pg/ml CSF. CSF BG analysis had good diagnostic performance in CM. CSF BG testing can be useful in CM, and a commercial kit is available. It will be of interest to correlate this with course, treatment, outcome, inflammation, and antigen. The only mycoses with common central nervous system (CNS) involvement are cryptococcal and coccidioidal, so CSF BG screening can be useful in meningitis diagnosis.