Several case reports and cohort studies have examined the use of (1,3)-beta-D-glucan measurement with cerebrospinal fluid to diagnose fungal meningitis. This systematic review aims to characterize the evidence regarding cerebrospinal fluid (1,3)-beta-D-glucan measurement to detect fungal meningitis. We searched PubMed for (1,3)-beta-D-glucan and each of several distinct fungi, cerebrospinal fluid, and meningitis. Summary data including diagnostic performance (where applicable) were recorded. A total of 939 records were examined via a PubMed search. One hundred eighteen records remained after duplicates were removed, and 104 records were excluded, as they did not examine cerebrospinal fluid, included animals, or focused on nonfungal infections. Fourteen studies were included in this systematic review. A variety of fungi, including species of Candida, Aspergillus, Exserohilum, Cryptococcus, Histoplasma, and Coccidioides, were studied, although most were case reports. Diagnostic accuracy was examined in 5 studies. Cerebrospinal fluid (CSF) (1,3)-beta-D-glucan measurement showed >95% sensitivity in the corticosteroid injection-related outbreak of Exserohilum rostratum. One study in Histoplasma meningitis found 53% (53/87) sensitivity and 87% (133/153) specificity, while another study of Cryptococcus meningitis found 89% (69/78) sensitivity and 85% (33/ 39) specificity. CSF (1,3)-beta-D-glucan testing may be useful, primarily as a nonspecific marker of fungal meningitis. Although the FDA black box warning states that Cryptococcus spp. do not make (1,3)-beta-D-glucan, the current evidence shows that (1,3)-beta-D-glucan is detectable in cryptococcal meningitis. Organism-specific testing should be used in conjunction with (1,3)-beta-D-glucan measurement.
Bibliographical noteFunding Information:
This publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under awards K23NS110470 and R01NS086312.
The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the writing of the manuscript or the choice to submit the manuscript. L.J.W. reports that he is the medical director, president, and founder of MiraVista Diagnostics. N.C.B. and D.R.B. received research funding from the National Institutes of Health during the completion of this study. The other authors declare no conflicts of interest.
© 2020 American Society for Microbiology. All Rights Reserved.
- Cerebrospinal fluid
- Coccidioides meningitis
- Cryptococcal meningitis
- Exserohilum rostratum
- Fungal meningitis
- Histoplasma meningitis