GeneXpert MTB/RIF explained

The Xpert MTB/RIF is a cartridge-based nucleic acid amplification test (NAAT) for 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),[1] Cepheid Inc. and Foundation for Innovative New Diagnostics, with additional financial support from the US National Institutes of Health (NIH).Tansey, Bernadette (25 March 2009). Cepheid unveils fast, low cost TB test, San Francisco Chronicle (lists creators, also states "Gene-based test developer Cepheid of Sunnyvale said Tuesday it has devised a rapid, sensitive diagnostic test for tuberculosis and will make it available at reduced cost in developing countries where the life-threatening disease is widespread.")

In December 2010, the World Health Organization (WHO) endorsed the Xpert MTB/RIF for use in tuberculosis (TB) endemic countries.[2] The announcement followed 18 months of assessing its field effectiveness in tuberculosis, MDR-TB, and TB/HIV co-infection.[3] The test may enable the diagnosis of TB in patients likely to be missed by traditional tests.[4]

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."

Description

The Xpert MTB/RIF detects DNA sequences specific for Mycobacterium tuberculosis and rifampicin resistance by polymerase chain reaction.[5] 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.[6] 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%.[7] 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.[8]

Cost

Some concerns have been raised about the Xpert MTB/RIF, including 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.[9] (6 August 2012). Public-Private Partnership Announces Immediate 40 Percent Cost Reduction for Rapid TB Test, Gates Foundation, Retrieved 15 September 2023(8 August 2012). Cepheid inks deals to sell TB test in developing nations, Reuters 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.[10]

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.[11] It is also used for COVID-19 testing at six sites across Somalia.[12] GeneXpert works as a rapid test for COVID-19 with a processing time of around 45 mins and with less cost.[13]

See also

External links

Notes and References

  1. https://www.who.int/tb/laboratory/xpert_faqs.pdf "Frequently asked questions on Xpert MTB/RIF assay"
  2. https://web.archive.org/web/20101210115147/http://www.who.int/mediacentre/news/releases/2010/tb_test_20101208/en/index.html "WHO endorses new rapid tuberculosis test"
  3. 10.1056/NEJMe1008496 . Tuberculosis Diagnosis — Time for a Game Change . 2010 . Small . Peter M. . Pai . Madhukar . New England Journal of Medicine . 363 . 11 . 1070–1071 . 20825320 .
  4. 10.1586/erm.10.67 . Xpert®MTB/RIF for point-of-care diagnosis of TB in high-HIV burden, resource-limited countries: Hype or hope? . 2010 . Rie . Annelies Van . Page-Shipp . Liesl . Scott . Lesley . Sanne . Ian . Stevens . Wendy . Expert Review of Molecular Diagnostics . 10 . 7 . 937–946 . 20964612 . 28312109 .
  5. 10.1128/jcm.01463-09 . Rapid Detection of Mycobacterium tuberculosis and Rifampin Resistance by Use of On-Demand, Near-Patient Technology . 2010 . Helb . Danica . Jones . Martin . Story . Elizabeth . Boehme . Catharina . Wallace . Ellen . Ho . Ken . Kop . Joann . Owens . Michelle R. . Rodgers . Richard . Banada . Padmapriya . Safi . Hassan . Blakemore . Robert . Lan . N. T. Ngoc . Jones-LóPez . Edward C. . Levi . Michael . Burday . Michele . Ayakaka . Irene . Mugerwa . Roy D. . McMillan . Bill . Winn-Deen . Emily . Christel . Lee . Dailey . Peter . Perkins . Mark D. . Persing . David H. . Alland . David . Journal of Clinical Microbiology . 48 . 1 . 229–237 . 19864480 . 2812290 .
  6. 10.1056/NEJMoa0907847 . Rapid Molecular Detection of Tuberculosis and Rifampin Resistance . 2010 . Boehme . Catharina C. . Nabeta . Pamela . Hillemann . Doris . Nicol . Mark P. . Shenai . Shubhada . Krapp . Fiorella . Allen . Jenny . Tahirli . Rasim . Blakemore . Robert . Rustomjee . Roxana . Milovic . Ana . Jones . Martin . O'Brien . Sean M. . Persing . David H. . Ruesch-Gerdes . Sabine . Gotuzzo . Eduardo . Rodrigues . Camilla . Alland . David . Perkins . Mark D. . New England Journal of Medicine . 363 . 11 . 1005–1015 . 20825313 . 2947799 .
  7. 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. 6 . CD009593. 10.1002/14651858.CD009593.pub4. 1469-493X. 6555588. 31173647.
  8. Catharina Boehme . Boehme CC, Nabeta P, Hillemann D, etal . 2010 . Rapid molecular detection of tuberculosis and rifampin resistance . New England Journal of Medicine. 363 . 11 . 1005–1015 . 10.1056/nejmoa0907847 . 2947799 . 20825313.
  9. Web site: Negotiated prices for Xpert® MTB/RIF and FIND country list . FIND Diagnostics . FIND . 6 April 2014 . October 2013 . dead . https://web.archive.org/web/20140407082202/http://www.finddiagnostics.org/about/what_we_do/successes/find-negotiated-prices/xpert_mtb_rif.html . April 7, 2014 .
  10. https://web.archive.org/web/20111130011752/http://www.who.int/tb/laboratory/mtbrifrollout/en/index.html "WHO monitoring of Xpert MTB/RIF rollout"
  11. Web site: Vietnam to use TB test for Covid-19. VnExpress. 8 August 2020. 8 August 2020. en. 21 September 2020. https://web.archive.org/web/20200921030347/https://e.vnexpress.net/news/news/vietnam-to-use-tb-test-for-covid-19-4143262.html. live.
  12. Web site: Jerving. Sara. Stigma and weak systems hamper the Somali COVID-19 response. Devex. 26 January 2021. 13 August 2020. 24 January 2021. https://web.archive.org/web/20210124003812/https://www.devex.com/news/stigma-and-weak-systems-hamper-the-somali-covid-19-response-97895. live.
  13. Journal of Family Medicine and Primary Care. 2020 . 7842456 . Singh . H. . Dhibar . D. P. . Old test for the diagnosis of novel corona virus infection: Role of GeneXpert in COVID-19 testing . 9 . 11 . 5822–5823 . 10.4103/jfmpc.jfmpc_1289_20 . 33532451 . free .