Evaluation of the Cepheid Xpert MTB/RIF assay

Abstract

The lack of capacity to provide laboratory confirmation of a diagnosis of tuberculosis disease (TB) is contributing to enormous gaps in the ability to find, treat and follow TB patients. WHO estimates that globally only about 57% of the notified new cases of pulmonary TB in 2012 and about 19% of rifampicin-resistant TB cases were laboratory confirmed. The Cepheid Xpert® MTB/RIF assay has been credited with revolutionizing laboratory testing to aid in the diagnosis of TB and rifampicin-resistant TB. This semi-automated test can detect both the causative agent of TB and mutations that confer rifampicin resistance from clinical specimens within 2 h after starting the test. In this article, we review the performance of the test, its pathway to regulatory approval and endorsement, guidelines for its use and lessons learned from the implementation of the test in low-burden, high-resource countries and in high-burden, low-resource countries.

Connectivity of diagnostic technologies: improving surveillance and accelerating tuberculosis elimination

“…Although device connectivity within other industries has been routine for some time, within the health care community it is still largely in its infancy. 6 In this paper, we discuss lessons learned from the global scale-up of the first generation of easy-toconnect diagnostic tools 7 and the pathway to tapping the potential of connectivity in the field of TB diagnostics. 8 …”

What tuberculosis can teach us about combating multidrug-resistant Gram negative bacilli

“…It is estimated that greater than 80% of MDR TB cases that arise each year remain microbiologically undiagnosed [53]. To address this limitation, significant resources have been invested in rapid, point-of-care molecular diagnostics for TB, leading to the development of line probe assays, fluorescence microscopy, liquid cultures, and the Xpert MTB/RIF assay [54]. Among these, the Xpert MTB/RIF assay, which simultaneously detects M. tuberculosis complex DNA and rifampin resistance (a reliable surrogate for MDR TB) [55] from clinical specimens within 2 h, and does not require specialized laboratory infrastructure or technologist skills, was selected for global roll-out.…”

“…Among these, the Xpert MTB/RIF assay, which simultaneously detects M. tuberculosis complex DNA and rifampin resistance (a reliable surrogate for MDR TB) [55] from clinical specimens within 2 h, and does not require specialized laboratory infrastructure or technologist skills, was selected for global roll-out. This assay was developed within 4 years through a collaboration among academic and industry partners, including Cepheid, FIND, University of Medicine and Dentistry of New Jersey (UMDNJ), the National Institutes of Health (NIH), and the Bill and Melinda Gates Foundation [54], [56], [57]. Critical for the development and programmatic implementation of this assay was the pooling of resources needed for test development, clinical validation trials, and field evaluations, and industry partners who agreed to flexible product pricing [57].…”

Quality of Sputum Specimen Samples Submitted for Culture and Drug Susceptibility Testing at the National Tuberculosis Reference Laboratory-Uganda, July-October 2013

“…These findings highlight the importance of expanding the roll-out of more sensitive diagnostic tests for TB and drug resistance for pulmonary tuberculosis in adults to peripheral laboratories in Uganda. The Xpert MTB/RIF assay is highly sensitive and specific and can detect TB and rifampicin resistance from clinical specimens within two hours after starting the test, with minimal requirements for facilities [18]. Even though culture and DST are still needed to detect TB in acid-fast bacilli-negative samples, confirm rifampicin resistance in persons at low risk of having MDR TB and determine susceptibilities to other anti-TB drugs, this new technology can help hasten detection and treatment of persons with MDR TB in Uganda.…”