The Xpert MTB/RIF is a cartridge-based, automated diagnostic test that can identify Mycobacterium tuberculosis (MTB) and resistance to rifampicin (RIF). It was co-developed by the laboratory of Professor David Alland at the University of Medicine and Dentistry of New Jersey (UMDNJ)., Cepheid, Inc. and Foundation for Innovative New Diagnostics, with additional financial support from the US National Institutes of Health (NIH).
In December 2010, the World Health Organization (WHO) endorsed the Xpert MTB/RIF for use in TB endemic countries and declared it a major milestone for global TB diagnosis. This followed 18 months of rigorous assessment of its field effectiveness in TB, MDR-TB and TB/HIV co-infection. This test, and others that are likely to follow, have the potential to revolutionize the diagnosis of TB.
Tuberculosis is one of the deadliest public health threats today. Traditionally, tuberculosis is mostly being diagnosed by a combination of chest X-rays, the staining of sputum with special dyes followed by microscopy, the growth of Mycobacterium tuberculosis in culture and the Mantoux test. The sputum smear microscopy is easy to do and is very cheap and combined with chest X-rays has been used for a long time by TB contro lagencies worldwide. However the sputum smear microscopy test has some problems in HIV-positive patients and children. Drug susceptibility could only be diagnosed from the growth of Mycobacterium tuberculosis in culture which can take as long as six weeks and fails in about 50% of the cases. The determination of drug susceptibility is particularly relevant because Mycobacterium tuberculosis becomes increasingly resistant to two of the major anti-tuberculosis drugs, isoniazide and rifampicin. This form of tuberculosis is called multi-drug-resistant tuberculosis (MDR-TB] is rapidly on the rise globally. MDR-TB cases need different antibiotics and are more difficult to treat owing to higher costs of drugs and longer regimens .
How the test works
The Xpert MTB/RIF detects DNA sequences specific for Mycobacterium tuberculosis and rifampicin resistance by polymerase chain reaction It is based on the Cepheid GeneXpert system, a platform for rapid and simple-to-use nucleic acid amplification tests (NAAT). The Xpert® MTB/RIF purifies and concentrates Mycobacterium tuberculosis bacilli from sputum samples, isolates genomic material from the captured bacteria by sonication and subsequently amplifies the genomic DNA by PCR. The process identifies all the clinically relevant Rifampicin resistance inducing mutations in the RNA polymerase beta (rpoB) gene in the Mycobacterium tuberculosis genome in a real time format using fluorescent probes called molecular beacons. Results are obtained from unprocessed sputum samples in 90 minutes, with minimal biohazard and very little technical training required to operate. This test was developed as an on-demand near patient technology which could be performed even in a doctor's office if necessary.
A review to assess the diagnostic accuracy of Xpert TB found that when used as an initial test to replace smear mircroscopy it had pooled sensitivity of 88% and specificity of 98% . However when Xpert TB was used as an add-on for cases of negative smear microscopy the sensitivity was only 67% and specificity 98%. 
Some concerns have been raised about the Xpert MTB/RIF, including minor operational issues and cost. The concessional price for a GeneXpert system is currently USD 17,000 for a four module instrument. As of 6 August 2012, the cost of a test cartridge in countries eligible for concessional pricing is USD 9.98. As of 30 June 2013, 1,402 GeneXpert systems (comprising 7553 modules) and >3 million Xpert MTB/RIF cartridges had been procured in 88 of the 145 countries under concessional pricing.
- "Frequently asked questions on Xpert MTB/RIF assay" Retrieved on 12 June 2012
- "WHO endorses new rapid tuberculosis test" 8 December 2010. Retrieved on 12 June 2012
- Small, P. M., Pai, M. (2010) "Tuberculosis diagnosis - time for a game change" N. Engl. J. Med. 363: 1070-1071
- Van Rie, A., Page-Shipp, L., Scott, L., Sanne, I., Stevens, W. (2010) "Xpert® MTB/RIF for point-of-care diagnosis of TB in high-HIV burden, resource-limited countries: hype or hope?" Expert Rev. Mol. Diagn. 10: 937-946
- Helb, D., et al (2010) "Rapid detection of Mycobacterium tuberculosis and Rifampin resistance by use of on-demand, near-patient technology. J. Clin. Microbiol. 48: 229-237
- Boehme, C. C., et al. (2010) "Rapid molecular detection of tuberculosis and rifampin resistance" N. Engl. J. Med. 363: 1005-1015
- Steingart KR et al.(2013) "Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults" Cochrane Database of Systematic Reviews 2013: DOI: 10.1002/14651858.CD009593.pub2.
- "Negotiated prices for Xpert® MTB/RIF and FIND country list" Foundation for Innovative New Diagnostics, August 2012. Retrieved on 14 November 2012
- "WHO monitoring of Xpert MTB/RIF rollout" World Health Organisation. Retrieved on 1 Sept 2013
- Frequently Asked Questions on Xpert MTB/RIF assay
- VIDEO: CNN features use of Xpert MTB/RIF in Uganda
- WHO Xpert technical and operational guide
- WHO Roadmap for rolling out Xpert MTB/RIF for rapid diagnosis of TB and MDR-TB
- Cepheid website on Xpert
- Cepheid Announces European Release of First On-Demand Molecular Test for Simultaneous Detection of Mycobacterium tuberculosis (TB) and Resistance to Rifampicin