Commercial Nucleic-Acid Amplification Tests for Diagnosis of Pulmonary Tuberculosis in Respiratory Specimens: Meta-Analysis and Meta-Regression

Abstract

BackgroundHundreds of studies have evaluated the diagnostic accuracy of nucleic-acid amplification tests (NAATs) for tuberculosis (TB). Commercial tests have been shown to give more consistent results than in-house assays. Previous meta-analyses have found high specificity but low and highly variable estimates of sensitivity. However, reasons for variability in study results have not been adequately explored. We performed a meta-analysis on the accuracy of commercial NAATs to diagnose pulmonary TB and meta-regression to identify factors that are associated with higher accuracy.Methodology/Principal FindingsWe identified 2948 citations from searching the literature. We found 402 articles that met our eligibility criteria. In the final analysis, 125 separate studies from 105 articles that reported NAAT results from respiratory specimens were included. The pooled sensitivity was 0.85 (range 0.36–1.00) and the pooled specificity was 0.97 (range 0.54–1.00). However, both measures were significantly heterogeneous (p<.001). We performed subgroup and meta-regression analyses to identify sources of heterogeneity. Even after stratifying by type of commercial test, we could not account for the variability. In the meta-regression, the threshold effect was significant (p = .01) and the use of other respiratory specimens besides sputum was associated with higher accuracy.Conclusions/SignificanceThe sensitivity and specificity estimates for commercial NAATs in respiratory specimens were highly variable, with sensitivity lower and more inconsistent than specificity. Thus, summary measures of diagnostic accuracy are not clinically meaningful. The use of different cut-off values and the use of specimens other than sputum could explain some of the observed heterogeneity. Based on these observations, commercial NAATs alone cannot be recommended to replace conventional tests for diagnosing pulmonary TB. Improvements in diagnostic accuracy, particularly sensitivity, need to be made in order for this expensive technology to be worthwhile and beneficial in low-resource countries.

Colorimetric microwell plate reverse-hybridization assay for Mycobacterium tuberculosis detection

“…The overall sensitivity (87%) and specificity (99%) results obtained in this study are in agreement with the findings of other studies and are also comparable with commercial kits (Pai et al 2003, Piersimoni & Scarparo 2003, Ling et al 2008. The sensitivity and specificity using the spontaneous sputum samples was high; 94% and 100%, respectively.…”

“…To improve the case-detection rate, many new molecular techniques have been developed for TB diagnosis, including commercially available kits and in-house methods. Among them, nucleic acid amplification (NAA) has been shown to be a very rapid and sensitive method (Greco et al 2006, Ling et al 2008. Early laboratory confirmation of TB leads to earlier treatment initiation, improved patient outcomes, more opportunities to interrupt transmission and more effective public health interventions (CDC 2009).…”

Standardization of a TaqMan-Based Real-Time PCR for the Detection of Mycobacterium tuberculosis-Complex in Human Sputum

“…6,40 To avoid sole-source reagents and equipment that can be difficult to import, afford, and sustain in some settings, we used a TaqMan real-time PCR assay and obtained sensitivity similar to the much slower Lö wenstein-Jensen culture.…”

“…The PCR is used in the diagnosis of several infectious diseases and can give results in a few hours. For TB diagnosis, multiple commercial and in-house nucleic acid amplification techniques have been developed 6,7 and recently, a commercial real-time PCR assay has been endorsed by the World Health Organization (WHO) (Xpert RIF/TB, GeneXpert, Cepheid, Canada) for the first time. 8 However, in-house PCR assays that use equipment and reagents that are available from diverse suppliers in competitive markets may be more affordable, feasible, and sustainable than using "sole-source" tests.…”

РЕТРОСПЕКТИВНА ЕВАЛУАЦИЈА COBAS AMPLICOR MTB ТЕСТА У ДЕТЕКЦИЈИ Mycobacterium tuberculosis ИЗ РЕСПИРАТОРНИХ УЗОРАКА

“…На ову, премда добру осјетљивост теста, утицали су 3 узорка спутума који су били негативни на COBAS AMPLICOR MTB Тесту. Ling et al, на основу резултата мета-анализе дијагностичке тачности комерцијалних амплификацијских тестова, наводе да је укупна осјетљивост за све респираторне узорке у односу на LJ културу била 85%, са значајном разликом у осјетљивости од 36% до 100% између различитих студија (Ling et al, 2008). Оваква хетерогеност у мета-анализи је усљед варијабилности у нивоима одлучивања, варијација у протоколима различитих тестова, спектра болести, те истраживане популације.…”