ss-D-Glucan Assay in the Cerebrospinal Fluid for the Diagnosis of non-cryptococcal Fungal Infection of the Central Nervous System: A Retrospective Multicentric Analysis and a Comprehensive Review of the Literature

Background Except for cryptococcosis, fungal infection of the central nervous system (FI-CNS) is a rare but severe complication. Clinical and radiological signs are non-specific, and the value of conventional mycological diagnosis is very low. This study aimed to assess the value of beta 1,3-D-glucan (BDG) detection in the cerebrospinal fluid (CSF) of non-neonatal non-cryptococcosis patients. Methods Cases associated with BDG assay in the CSF performed in 3 French University Hospitals over 5 years were included. Clinical, radiological, and mycological results were used to classify the episodes as proven/highly probable, probable, excluded, and unclassified FI-CNS. Sensitivity and specificity were compared to that calculated from an exhaustive review of the literature. Results In total, 228 episodes consisting of 4, 7, 177, and 40 proven/highly probable, probable, excluded, and unclassified FI-CNS, respectively, were analysed. The sensitivity of BDG assay in CSF to diagnose proven/highly probable/probable FI-CNS ranged from 72.7% [95% confidence interval {CI}: 43.4%-90.2%] to 100% [95% CI: 51%-100%] in our study and was 82% in the literature. For the first time, specificity could be calculated over a large panel of pertinent controls and was found at 81.8% [95% CI: 75.3%-86.8%]. Bacterial neurologic infections were associated with several false positive results Conclusions Despite its sub-optimal performance, BDG assay in the CSF should be added to the diagnostic armamentarium for FI-CNS. Although presenting sub-optimal performances (sensitivity: 72.7%-100% and specificity: 81.8%), beta 1,3-D-glucan (BDG) assay should be added to the panel of biomarkers to test in the cerebrospinal fluid (CSF) for the challenging diagnosis of fungal infections of the CNS.

Automated summary

This study assessed the value of beta 1,3-D-glucan (BDG) detection in the cerebrospinal fluid (CSF) of non-neonatal non-cryptococcosis patients. The results showed that the sensitivity of BDG assay in diagnosing proven/highly probable/probable FI-CNS ranged from 72.7% to 100%, and the specificity was found to be 81.8%. Despite its sub-optimal performance, BDG assay should be added to the diagnostic armamentarium for FI-CNS.