Diagnostic accuracy of the loop-mediated isothermal amplification assay for extrapulmonary tuberculosis: A meta-analysis

Abstract

Background: Loop-mediated isothermal amplification (LAMP) is used to detect pulmonary tuberculosis (PTB); however, the diagnostic accuracy of the LAMP assay for extrapulmonary tuberculosis (EPTB) is unclear. We performed a meta-analysis to evaluate the performance of LAMP in the detection of EPTB.

Methods: We searched PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wanfang database for studies published before Sep 16, 2017. We reviewed studies and compared the performance of LAMP with that of a composite reference standard (CRS) and culture for clinically suspected EPTB. We used a bivariate random-effects model to perform meta-analyses and used meta-regression and subgroup analysis to analyze sources of heterogeneity.

Results: Fourteen articles including 24 independent studies (16 compared LAMP to CRS, 8 to culture) of EPTB were identified. LAMP showed a pooled sensitivity of 77% (95% confidence interval (CI) 68-85), specificity of 99% (95% CI 96-100), and area under SROC curves (AUC) of 0.96 (95% CI 0.94-0.97) against CRS. It showed a pooled sensitivity of 93% (95% CI 88-96), specificity of 77% (95% CI 64-86), and AUC of 0.94 (95% CI 0.92-0.96) against culture. The pooled sensitivity, specificity, and AUC of MPB64 LAMP were 86% (95% CI 86-86), 100% (95% CI 100-100), and 0.97 (95% CI 0.95-0.98), respectively, and those of IS6110 LAMP were 75% (95% CI 64-84), 99% (95% CI 90-100), and 0.91 (95% CI 0.88-0.93), respectively, compared with CRS.

Conclusions: These results suggest good diagnostic efficacy of LAMP in the detection of EPTB. Additionally, the diagnostic efficacy of MPB64 LAMP was superior to that of IS6110 LAMP.

Fig 1. Literature retrieval flow chart.

Searches of PubMed, the Cochrane Library, Embase, Wanfang database and CNKI returned 264, 11, 328, 98, and 99 articles, respectively.

Fig 2. Methodological quality graphs (risk of bias and applicability concerns) as percentages across the included studies.

a: composite reference standard. b: culture reference standard.

Fig 3. Forest plot of LAMP sensitivity and specificity for tuberculosis detection in EPTB.

a: composite reference standard. b: culture reference standard. The squares represent the sensitivity and specificity of a study, and the black line their confidence intervals. The diamonds represent the pooled sensitivity and specificity and their confidence intervals. LAMP: loop-mediated isothermal amplification; EPTB: extrapulmonary tuberculosis.

Fig 4. Forest plot of LAMP sensitivity and specificity for tuberculosis detection using different target genes against a composite reference standard.

a: MPB64. b: IS6110. The squares represent the sensitivity and specificity of one study, and the black line their confidence intervals. The diamonds represent the pooled sensitivity and specificity and their confidence intervals. LAMP: loop-mediated isothermal amplification.

Fig 5. Forest plot of LAMP sensitivity and specificity using cerebrospinal fluid samples against a composite reference standard.

The squares represent the sensitivity and specificity of one study, and the black line their confidence intervals. The diamonds represent the pooled sensitivity and specificity and their confidence intervals. LAMP: loop-mediated isothermal amplification.