Cerebrospinal fluid AFB smear in adults with tuberculous meningitis: A systematic review and diagnostic test accuracy meta-analysis

Abstract

Background: Cerebrospinal fluid (CSF) Ziehl-Neelsen acid-fast bacilli (AFB) smear is a rapid, cheap, widely available test for tuberculous meningitis (TBM). Yet, reported test sensitivity is highly variable. We performed a systematic review and meta-analysis for CSF AFB smear vs. other mycobacterial tests to diagnose TBM.

Methods: We searched MEDLINE and Embase for studies reporting sensitivity and specificity of AFB smear against mycobacterial tests (reference standard) in adults (≥15 years) with suspected TBM. We used the QUADAS-2 tool to assess risk of bias. We estimated pooled sensitivity and specificity of AFB smear versus the reference standard using random-effects bivariate modeling. We used the I² statistic to assess heterogeneity between studies.

Results: Of 981 articles identified, 11 were eligible for inclusion with a total of 1713 participants. Seven studies were from high-TB burden settings and 4 from low-TB burden settings. The pooled sensitivity and specificity of CSF AFB smear were 8% (95%CI 3-21) and 100% (95%CI 90-100), with substantial heterogeneity in diagnostic performance (I² >95% for both) and reference standards.

Conclusion: CSF AFB smear has poor sensitivity in most settings. If other more sensitive tests are available, those should be used preferentially rather than CSF AFB smear.

Keywords: Acid-fast bacilli; Meta-analysis; Systematic review; Tuberculous meningitis; Ziehl-neelsen stain.

Figure 1:

PRISMA Flow Diagram of Study Selection Process

Figure 2:

Diagnostic sensitivity and specificity of AFB Smear versus reference standard TP=true positive, FN=false negative, FP=false positive, TN=true negative Meta-analysis of the diagnosis of tuberculous mdeningitis in the 11 studies included. Reference standards for each of the studies included some combination of AFB smear, CSF profile, M. tuberculosis culture, NAAT, B symptom evaluation, and/or the Uniform Tuberculous Meningitis Case Definition (Marais criteria). Dashed vertical lines show the pooled estimates. I² shows inter-study heterogeneity.

Figure 3:

Hierarchical summary receiver operating characteristic (ROC) curve meta-analysis of diagnostic performance of AFB smear versus reference standard HSROC=hierarchical summary receiver operating characteristic curve Area under the hierarchical summary ROC curve C-statistic is 0·74 (95% CI 0·70–0·77). The confidence region shows the range that is likely to contain the population summary operating point and the prediction region is the range that is likely to contain where study data that are not yet observed would fall. Circle size corresponds to sample size in the included studies, where larger circles indicate larger sample sizes relative to other included studies.