Interferon-γ release assays for tuberculous meningitis diagnosis: a meta-analysis

Introduction: Tuberculous meningitis (TBM) is still a great challenge to global public health. As conventional diagnostic methods for TBM are unsatisfactory, interferon-gamma release assays (IGRAs) have been introduced for TBM diagnosis tentatively. However, the role of IGRAs for diagnosing TBM remains unclear. Thus, we systematically evaluated the diagnostic performance of cerebrospinal fluid (CSF) and peripheral blood (PB) IGRAs in TBM to fill this blank. Material and methods: Relevant studies were systematically searched in both foreign and Chinese databases up to March 2018. Studies in which TBM diagnosis was based on microbiological or clinical criteria were included. The quality of the included studies was assessed through the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Main outcome measures, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR), were pooled statistically using random effects models. The potential heterogeneity was explored by threshold effect analysis, subgroup analyses and meta-regression. Funnel plots and Egger's test were used to test the potential publication bias. Statistical analyses were performed using Stata and Meta-DiSc software. Results: Twenty-six out of 656 publications were eligible for meta-analysis, including 1892 participants in total. The pooled estimates of PB IGRAs for TBM diagnosis are as follows: sensitivity: 0.81 (95% CI: 0.78-0.84); specificity: 0.76 (95% CI: 0.73-0.78); PLR: 4.23 (95% CI: 2.95-6.07); NLR: 0.24 (95% CI: 0.19-0.32) and DOR: 21.06 (11.91-37.24). The corresponding estimates for CSF IGRAs were obtained: sensitivity: 0.81 (95% CI: 0.76-0.85); specificity: 0.89 (95% CI: 0.86-0.92); PLR: 7.87 (95% CI: 4.98-12.46); NLR: 0.19 (95% CI: 0.13-0.29); and DOR: 47.74 (25.02-91.12). Conclusions: The diagnostic performance of IGRAs is suboptimal. In terms of cost, turn-around time and accessibility, these assays are unsuitable for use as biomarkers for TBM diagnosis.