Rapid molecular TB diagnosis: evidence, policy making and global implementation of Xpert MTB/RIF

Abstract

If tuberculosis (TB) is to be eliminated as a global health problem in the foreseeable future, improved detection of patients, earlier diagnosis and timely identification of rifampicin resistance will be critical. New diagnostics released in recent years have improved this perspective but they require investments in laboratory infrastructure, biosafety and staff specialisation beyond the means of many resource-constrained settings where most patients live. Xpert MTB/RIF, a new assay employing automated nucleic acid amplification to detect Mycobacterium tuberculosis, as well as mutations that confer rifampicin resistance, holds the promise to largely overcome these operational challenges. In this article we position Xpert MTB/RIF in today's TB diagnostic landscape and describe its additional potential as an adjunct to surveillance and surveys, taking into account considerations of pricing and ethics. In what could serve as a model for the future formulation of new policy on diagnostics, we trace the unique process by which the World Health Organization consulted international expertise and systematically assessed published evidence and freshly emerging experience from the field ahead of its endorsement of the Xpert MTB/RIF technology in 2010, summarise subsequent research findings and guidance on who to test and how, and provide perspectives on scaling up the new technology.

Performance of Xpert MTB/RIF on pleural tissue for the diagnosis of pleural tuberculosis: Table 1–

“…Explanations for the limited sensitivity of Xpert in pleural fluid and tissue samples could relate to PCR inhibitors or insufficient sample volume in this paucibacillary disease. Further research on the optimisation of sample processing should be considered to enhance the sensitivity of the test [4]. In summary, our findings suggest that Xpert is of limited use in the diagnosis of pleural TB.…”

“…However, the preferred specimen for the diagnosis of pleural TB is pleural tissue. To date, the evaluation of Xpert performed on pleural tissue has been limited to isolated samples within larger studies [4,6,7].…”

“…The Xpert MTB/RIF assay (Xpert; Cepheid, Sunnyvale, CA, USA) is a rapid, World Health Organization (WHO) endorsed, automated PCR test optimised for respiratory specimens that can detect both Mycobacterium tuberculosis (MTB) and rifampicin resistance [3,4]. Given the limitations of available tests for the diagnosis of pleural TB, several studies have evaluated the performance of Xpert using pleural fluid as a sample type.…”

“…However, the preferred specimen for the diagnosis of pleural TB is pleural tissue. To date, the evaluation of Xpert performed on pleural tissue has been limited to isolated samples within larger studies [4,6,7].We enrolled consecutive adult patients that were evaluated for pleural TB in the pulmonary clinic and inpatient ward at the Christian Medical College, Vellore, India. Pleural TB was suspected based on clinical symptoms and radiographic evidence of a pleural effusion.…”

Pulmonary Tuberculosis Management: 2015 Update

“…As part of pillar 1, universal drug susceptibility testing (rapid DST with, for example GeneXpert 17 and/or conventional with solid or liquid culture) is strongly recommended before prescribing the anti-TB regimen; however, this is not universally available yet in several developing countries. Re-treatment patients need special attention because of the risk of inducing drug resistance.…”