Diagnostic Accuracy of Cerebrospinal Fluid (CSF) Adenosine Deaminase (ADA) for Tuberculous Meningitis (TBM) in Adults: A Systematic Review and Meta-Analysis

Abstract

Tuberculous meningitis is the most serious complication of tuberculosis. Early diagnosis is crucial to start relevant treatment to prevent death and disability. Electronic databases PubMed, Google Scholar, and Cochrane Library were used to find relevant articles from January 1980 to June 2022. The random-effect model in terms of pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval was adopted to derive the diagnostic efficacy of cerebrospinal fluid (CSF) adenosine deaminase (ADA) for the diagnosis of tuberculous meningitis (TBM) in adult patients. A total of 22 studies (20 prospective and two retrospective data) have been included in this meta-analysis, having 1927 participants. We perceived acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROCs), and diagnostic odds ratio (DOR) of 0.85 (95% CI: 0.77-0.90), 0.90 (95% CI: 0.85-0.93), 0.94 (95% CI: 0.91-0.96) and 48 (95% CI: 26-86), respectively, for CSF-ADA for differentiating TBM from non-TBM in adult patients. To ascertain the certainty of evidence for CSF-ADA as a diagnostic marker for TBM, Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) analysis was used. CSF-ADA is an auspicious diagnostic test with a high degree of specificity and acceptable sensitivity for the diagnosis of tuberculous meningitis, however, with very low certainty of evidence.

Keywords: csf-ada; diagnostic accuracy; meningitis; meta-analysis; systematic review; tuberculous.

Figure 1. PRISMA flow diagram representing selection and inclusion of different studies.

PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Figure 2. Risk of bias and applicability concerns graph: review author's judgments about each domain presented as percentages across included studies.

Figure 3. Risk of bias and applicability concerns summary: review author's judgment about each domain for each included study.

Figure 4. Forest plot of pooled sensitivity and pooled specificity of CSF-ADA in the diagnosis of TBM.

CSF: cerebrospinal fluid; ADA: adenosine deaminase; TBM: tuberculous meningitis

Figure 5. Summary ROC curve with prediction and confidence contours showing the discriminatory power of CSF-ADA for diagnosis of TBM.

ROC: receiver operating characteristic; CSF: cerebrospinal fluid; ADA: adenosine deaminase; TBM: tuberculous meningitis

Figure 6. Fagan nomogram of CSF-ADA. Nomogram analysis showing pre-test and post-test probability of CSF-ADA in the diagnosis of TBM.

CSF: cerebrospinal fluid; ADA: adenosine deaminase; TBM: tuberculous meningitis

Figure 7. Deek's funnel plot for assessing the risk of publication bias.

Figure 8. Meta-regression analysis showing the source of heterogeneity might be due to the sample size, reference standard, ADA assay method, and CSF-ADA cut-off value in the study.

CSF: cerebrospinal fluid; ADA: adenosine deaminase