Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults

Abstract

Background Accurate, rapid detection of tuberculosis (TB) and TB drug resistance is critical for improving patient care and decreasing TB transmission. Xpert® MTB/RIF assay is an automated test that can detect both TB and rifampicin resistance, generally within two hours after starting the test, with minimal hands‐on technical time. The World Health Organization (WHO) issued initial recommendations on Xpert® MTB/RIF in early 2011. A Cochrane Review on the diagnostic accuracy of Xpert® MTB/RIF for pulmonary TB and rifampicin resistance was published January 2013. We performed this updated Cochrane Review as part of a WHO process to develop updated guidelines on the use of the test. Objectives To assess the diagnostic accuracy of Xpert® MTB/RIF for pulmonary TB (TB detection), where Xpert® MTB/RIF was used as both an initial test replacing microscopy and an add‐on test following a negative smear microscopy result. To assess the diagnostic accuracy of Xpert® MTB/RIF for rifampicin resistance detection, where Xpert® MTB/RIF was used as the initial test replacing culture‐based drug susceptibility testing (DST). The populations of interest were adults presumed to have pulmonary, rifampicin‐resistant or multidrug‐resistant TB (MDR‐TB), with or without HIV infection. The settings of interest were intermediate‐ and peripheral‐level laboratories. The latter may be associated with primary health care facilities. Search methods We searched for publications in any language up to 7 February 2013 in the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; ISI Web of Knowledge; MEDION; LILACS; BIOSIS; and SCOPUS. We also searched the metaRegister of Controlled Trials (mRCT) and the search portal of the WHO International Clinical Trials Registry Platform to identify ongoing trials. Selection criteria We included randomized controlled trials, cross‐sectional studies, and cohort studies using respiratory specimens that allowed for extraction of data evaluating Xpert® MTB/RIF against the reference standard. We excluded gastric fluid specimens. The reference standard for TB was culture and for rifampicin resistance was phenotypic culture‐based DST. Data collection and analysis For each study, two review authors independently extracted data using a standardized form. When possible, we extracted data for subgroups by smear and HIV status. We assessed the quality of studies using QUADAS‐2 and carried out meta‐analyses to estimate pooled sensitivity and specificity of Xpert® MTB/RIF separately for TB detection and rifampicin resistance detection. For TB detection, we performed the majority of analyses using a bivariate random‐effects model and compared the sensitivity of Xpert® MTB/RIF and smear microscopy against culture as reference standard. For rifampicin resistance detection, we undertook univariate meta‐analyses for sensitivity and sp...

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…An example of a silent mutation can be seen in rpoB (TTC→TTT; Phe514Phe), which does not result in an aminoacid change, and tests that only detect changes at that nucleotide position without identifying the nucleotide involved might give false-positive resistance results. 246 Regardless, the high sensitivity and specificity of the molecular targets (SNPs) for rifampicin resistance, 247 and their value as a tool for predicting MDR tuberculosis has supported commercial in-vitro diagnostic products to enter the market.…”

“…250 Concerns about the accuracy of the Xpert MTB/RIF test and reports of false-positive rifampicin resistance results have led countries such as Brazil and South Africa to adopt a policy of confirmatory testing. 247,[251][252][253][254] The manufacturers have reported that a new version of the Xpert MTB/RIF test is under development (Xpert ULTRA) in which the diagnostic targets and rifampicin-resistance detection chemistry have been changed, with the aim of increasing test accuracy. The test is being assessed by its developers and is expected to be released for sale and independent assessment in 2017.…”

Impacto orçamentário da incorporação do GeneXpert MTB/RIF para o diagnóstico da tuberculose pulmonar na perspectiva do Sistema Único de Saúde, Brasil, 2013-2017

“…Entretanto, diante das limitações desse teste convencional para o diagnóstico da TB, novas tecnologias surgiram, como o Xpert MTB/RIF, teste molecular rápido realizado no sistema GeneXpert MTB/RIF, para a detecção do Mycobacterium tuberculosis e da resistência à rifampicina 6,7 . O Xpert MTB/RIF é particularmente útil nos países com altas taxas de TB-multirresistente (TB-MDR, resistente à rifampicina e isoniazida), como o Peru, responsável por 32% dos casos na região 1,2 .…”

Understanding the incremental value of novel diagnostic tests for tuberculosis

“…Nevertheless, the link between improved diagnostic sensitivity and better TB detection remains uncertain. Studies [8][9][10][11] in different settings have found little or no change in the number of pulmonary TB diagnoses or deaths when comparing sputum smear microscopy and Xpert MTB/RIF, a more sensitive molecular test 12 . This result may reflect high levels of empirical treatment among people who test negative [13][14][15] .…”