Nucleic acid amplification tests in the diagnosis of tuberculous pleuritis: a systematic review and meta-analysis

Abstract

Background: Conventional tests for tuberculous pleuritis have several limitations. A variety of new, rapid tests such as nucleic acid amplification tests--including polymerase chain reaction--have been evaluated in recent times. We conducted a systematic review to determine the accuracy of nucleic acid amplification (NAA) tests in the diagnosis of tuberculous pleuritis.

Methods: A systematic review and meta-analysis of 38 English and Spanish articles (with 40 studies), identified via searches of six electronic databases, hand searching of selected journals, and contact with authors, experts, and test manufacturers. Sensitivity, specificity, and other measures of accuracy were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Heterogeneity in study results was formally explored using subgroup analyses.

Results: Of the 40 studies included, 26 used in-house ("home-brew") tests, and 14 used commercial tests. Commercial tests had a low overall sensitivity (0.62; 95% confidence interval [CI] 0.43, 0.77), and high specificity (0.98; 95% CI 0.96, 0.98). The positive and negative likelihood ratios for commercial tests were 25.4 (95% CI 16.2, 40.0) and 0.40 (95% CI 0.24, 0.67), respectively. All commercial tests had consistently high specificity estimates; the sensitivity estimates, however, were heterogeneous across studies. With the in-house tests, both sensitivity and specificity estimates were significantly heterogeneous. Clinically meaningful summary estimates could not be determined for in-house tests.

Conclusions: Our results suggest that commercial NAA tests may have a potential role in confirming (ruling in) tuberculous pleuritis. However, these tests have low and variable sensitivity and, therefore, may not be useful in excluding (ruling out) the disease. NAA test results, therefore, cannot replace conventional tests; they need to be interpreted in parallel with clinical findings and results of conventional tests. The accuracy of in-house nucleic acid amplification tests is poorly defined because of heterogeneity in study results. The clinical applicability of in-house NAA tests remains unclear.

Figure 1

Study selection process

Figure 2

Forest plots of estimates of sensitivity and specificity in studies with commercial and in-house tests. The point estimates of sensitivity and specificity from each study are shown as solid circles. Error bars are 95% confidence intervals. Numbers indicate the studies cited in the bibliography. Pooled estimates are summary random effects estimates with 95% confidence intervals.

Figure 3

Summary Receiver Operating Characteristic curves for commercial and in-house tests Each solid circle represents each study in the meta-analysis. The size of each study is indicated by the size of the solid circle. The weighted (dark line) and unweighted (thin line) regression SROC curves summarize the overall diagnostic accuracy.

Figure 4

Funnel plot for evaluation of publication bias in studies with in-house tests The funnel graph plots the log of the diagnostic odds ratio (DOR) against the standard error of the log of the DOR (an indicator of sample size). Each open circle represents each study in the meta-analysis. The line in the center indicates the summary DOR. In the absence of publication bias, the DOR estimates from smaller studies are expected to be scattered above and below the summary estimate, producing a triangular or funnel shape. The funnel plots appear asymmetric – smaller studies with low DOR estimates are missing – indicating a potential for publication bias. The Egger test for publication bias was statistically significant (p = 0.002) in the in-house test subgroup.