Cerebrospinal fluid galactomannan detection for the diagnosis of central nervous system aspergillosis: a diagnostic test accuracy systematic review and meta-analysis

Background

Cerebrospinal fluid (CSF) galactomannan is an adjunctive test for central nervous system (CNS) aspergillosis diagnosis with unclear diagnostic test characteristics.

Objectives

To evaluate the diagnostic test characteristics of CSF galactomannan in CNS aspergillosis.

Methods

Systematic review and meta-analysis.

Data sources

MEDLINE, Embase, Web of Science, and Scopus, from inception to 24 February 2023.

Study eligibility criteria

Prospective and retrospective studies with 1-group and 2-group designs using any galactomannan assay on CSF to diagnose CNS aspergillosis.

Participants

Adult and/or paediatric patients with CNS aspergillosis.

Test(s)

Galactomannan testing on CSF specimens.

Reference standard

European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) diagnostic criteria, or equivalent.

Assessment of risk of bias

QUADAS-2 assessment in duplicate.

Methods of data synthesis

Bivariate restricted maximum likelihood estimation random-effects meta-analysis, summarized using forest and summary receiver operating characteristic plots; bivariate meta-regression models to investigate heterogeneity; and subgroup and sensitivity analyses to explore subgroup effects and methodologic choices (PROSPERO registration: CRD42022296331; funding: none).

Results

We included eight studies (n = 342 participants). The summary estimates of CSF galactomannan sensitivity and specificity were 69.0% (95% CI, 57.2–78.7%) and 94.4% (95% CI, 82.8–98.3%), respectively. Using meta-regression, galactomannan cut-off (p = 0.38), EORTC/MSGERC criteria version (p = 0.48), or whether the reference standard was defined as both proven and probable or only proven aspergillosis (p = 0.48) did not explain observed heterogeneity. No subgroup effects were demonstrated by analysing the EORTC/MSGERC criteria reference standard used (e.g. 2002 vs. 2008 definitions) or whether paediatric patients were included. Diagnostic sensitivity was improved using a galactomannan cut-off of 1.0, and by excluding high risk of bias and 1-group design studies.

Discussion

CSF galactomannan is a highly specific but insensitive test for use as a component of CNS aspergillosis diagnosis. Few included studies, no prospective studies, and a high risk of bias are study limitations.