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The Xpert MTB/RIF is a cartridge-based nucleic acid amplification test (NAAT) for simultaneous rapid tuberculosis diagnosis and rapid antibiotic sensitivity test. It is an automated diagnostic test that can identify Mycobacterium tuberculosis (MTB) DNA 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 tuberculosis (TB) endemic countries. This followed 18 months of assessment of its field effectiveness in TB, MDR-TB and TB/HIV co-infection. The test may enable the diagnosis of TB in patients likely to be missed by traditional tests.
According to the Centers for Disease Control and Prevention (CDC) in 2015, the Xpert MTB/RIF test was "revolutionizing TB control by contributing to the rapid diagnosis of TB disease and drug resistance. The test simultaneously detects Mycobacterium tuberculosis complex (MTBC) and resistance to rifampin (RIF) in less than 2 hours. In comparison, standard cultures can take 2 to 6 weeks for MTBC to grow and conventional drug resistance tests can add 3 more weeks."
Traditionally, tuberculosis is mostly diagnosed by a combination of chest X-rays, staining of sputum with special dyes followed by microscopy, growth of Mycobacterium tuberculosis in culture and the Mantoux test. The sputum smear microscopy is easily carried out and very cheap, and has been used for a long time by TB control agencies worldwide, combined with chest X-rays. However the test is not always accurate in HIV-positive patients, children, and patients with low bacterial load. The Xpert MTB/RIF test is highly sensitive in detecting pulmonary TB disease. An in vitro study demonstrated a limit of detection of as few as 131 colony-forming units/mL of MTB, compared with approximately 10,000 colony-forming units/mL with conventional smear microscopy. Drug susceptibility could only be diagnosed from the growth of Mycobacterium tuberculosis in culture which can take as long as six weeks and needs high bio safety labs and is costly. 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 .
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 rapid, simple-to-use nucleic acid amplification test (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 most of 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 microscopy it had pooled sensitivity of 89% and specificity of 99% . However, when Xpert TB was used as an add-on for cases of negative smear microscopy the sensitivity was only 67% and specificity 99%. In a clinical study conducted the sensitivity of the MTB/RIF test on just 1 sputum sample was 92.2% for culture-positive TB; 98.2% for smear+ and culture-positive cases; and 72.5% for smear-negative, culture-positive cases, with a specificity of 99.2%. Sensitivity and higher specificity were slightly higher when 3 samples were tested.
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 32,000 USD for a four module instrument. As of 6 August 2012, the cost of a test cartridge in countries eligible for concessional pricing is 9.98 USD.[better source needed] 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.
Using for COVID-19 testing
In August 2020, Vietnam Ministry of Health had approved the use of GeneXpert, that has been used in Vietnam tuberculosis prevention network since 2012, for COVID-19 testing. According to Nguyen Viet Nhung, director of the National Lung Hospital in Hanoi, the test is similar to RT-PCR, gives accurate results within 35–45 minutes for both COVID-19 and tuberculosis and could work automatically. It is also used for COVID-19 testing at six sites across Somalia.
- Cepheid Inc. (the manufacturer)
- "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
- Centers for Disease Control and Prevention (2015), "A New Tool to Diagnose Tuberculosis: The Xpert MTB/RIF Assay" (PDF), CDC website, archived from the original (PDF) on 2017-12-17, retrieved 2018-05-25.
- "A New Era: Molecular Tuberculosis Diagnosis".
- 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
- Horne, David J.; Kohli, Mikashmi; Zifodya, Jerry S.; Schiller, Ian; Dendukuri, Nandini; Tollefson, Deanna; Schumacher, Samuel G.; Ochodo, Eleanor A.; Pai, Madhukar; Steingart, Karen R. (7 June 2019). "Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults". The Cochrane Database of Systematic Reviews. 6: CD009593. doi:10.1002/14651858.CD009593.pub4. ISSN 1469-493X. PMC 6555588. PMID 31173647.
- Boehme CC, Nabeta P, Hillemann D, et al. (2010). "Rapid molecular detection of tuberculosis and rifampin resistance". N Engl J Med. 363 (11): 1005–1015. doi:10.1056/nejmoa0907847. PMC 2947799. PMID 20825313.
- "Negotiated prices for Xpert® MTB/RIF and FIND country list". FIND Diagnostics. FIND. October 2013. Archived from the original on April 7, 2014. Retrieved 6 April 2014.
- "WHO monitoring of Xpert MTB/RIF rollout" World Health Organisation. Retrieved on 1 Sept 2013
- "Vietnam to use TB test for Covid-19". VnExpress. 8 August 2020. Retrieved 8 August 2020.
- Jerving, Sara (13 August 2020). "Stigma and weak systems hamper the Somali COVID-19 response". Devex. Retrieved 26 January 2021.
- Frequently Asked Questions on Xpert MTB/RIF assay
- VIDEO: CNN features use of Xpert MTB/RIF in Uganda
- WHO Xpert technical and operational guide[permanent dead link]
- 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