Diagnostic test accuracy of loop-mediated isothermal amplification assay for Mycobacterium tuberculosis: systematic review and meta-analysis

Abstract

Diagnostic test accuracy of the loop-mediated isothermal amplification (LAMP) assay for culture proven tuberculosis is unclear. We searched electronic databases for both cohort and case-control studies that provided data to calculate sensitivity and specificity. The index test was any LAMP assay including both commercialized kits and in-house assays. Culture-proven M. tuberculosis was considered a positive reference test. We included 26 studies on 9330 sputum samples and one study on 315 extra-pulmonary specimens. For sputum samples, 26 studies yielded the summary estimates of sensitivity of 89.6% (95% CI 85.6–92.6%), specificity of 94.0% (95% CI 91.0–96.1%), and a diagnostic odds ratio of 145 (95% CI 93–226). Nine studies focusing on Loopamp MTBC yielded the summary estimates of sensitivity of 80.9% (95% CI 76.0–85.1%) and specificity of 96.5% (95% CI 94.7–97.7%). Loopamp MTBC had higher sensitivity and lower specificity for smear-positive sputa compared to smear-negative sputa. In-house assays showed higher sensitivity and lower specificity compared to Loopamp MTBC. LAMP promises to be a useful test for the diagnosis of TB, however there is still need to improve the assay to make it simpler, cheaper and more efficient to make it competitive against other PCR methods already available.

Performance and Impact of GeneXpert MTB/RIF® and Loopamp MTBC Detection Kit® Assays on Tuberculosis Case Detection in Madagascar

“…These results agree with pooled median sensitivity of 88.0% (95% CI 83.0-92.0%) and specificity of 98.0% (95% CI 97.0-99.0%) reported in a Cochrane Review of fifteen studies assessing the performance of GeneXpert MTB/RIF® on sputum samples [3]. Similarly, with a sensitivity of 84.6% (95% CI 78.9-89.0%) and a specificity of 98.4% (95% CI 96.2-99.4%), Loopamp MTBC Detection Kit® performance was found comparable to reports observed from the literature [2]. For both molecular assays, this agreement between locally assessed performance and reported literature data was maintained when analyzing the smear-positive and smear-negative sub-groups of isolates.…”

“…To bypass the inconvenient delays and biosecurity requirements associated with bacterial culture, GeneXpert MTB/RIF® (Cepheid; USA) polymerase chain reaction (PCR) and Loopamp MTBC Detection Kit® (Eiken Chemical Co; Japan) loop-mediated isothermal amplification (LAMP)-based molecular assays were developed, validated on direct sputum samples and endorsed by the World Health Organization (WHO) respectively in 2013 and 2016 [2,3]. Those assays can either be used as first-line testing in place of sputum smear microscopy or as a follow-on test in adults with symptoms of pulmonary TB but testing negative on smear microscopy [4,5].…”

Comparison of Loop-Mediated Isothermal Amplification, Microscopy, Culture, and PCR for Diagnosis of Pulmonary Tuberculosis

“…There are several published reports on the diagnostic potential of LAMP assays for TB diagnosis. The overall performance varied greatly across the studies (5, [14][15][16][17].…”

Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Active Tuberculosis Patients

“…Immunological tests are time consuming and require confirmation in longitudinal analyses and further functional studies [4]. New automatic molecular methods for the diagnosis of TB are currently available, but the cost per test is too high for resource-limited settings [5]. Therefore, new rapid, sensitive and cost-effective biomarkers or methods for TB diagnosis are urgently needed.…”