TB or not TB? That is the question (and here’s the test that can answer it)

Key message: Xpert MTB/RIF is a diagnostic test which can quickly detect pulmonary tuberculosis and rifampicin resistance in adults, with a high degree of accuracy and without the need for laboratory facilities, allowing treatment to be started quickly.

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is spread from person to person through the air and most commonly affects the lungs (pulmonary tuberculosis or PTB) but may affect any other organ or tissue (extrapulmonary tuberculosis).  Tuberculosis has been with us since ancient times and is now the most common infection-related cause of death worldwide, as well as one of the top 10 causes of death overall (WHO Global TB Report 2018). In 2017, 10 million people developed TB (of whom 9% also had HIV) and 1.6 million died from it, yet it’s a disease that is largely curable if detected early and effectively treated (WHO Global TB Report 2018). Ending the TB epidemic by 2030 is one of the health targets of the Sustainable Development Goals.

Postage stamp showing Robert Koch

Dr Robert Koch discovered the tuberculosis bacillus in 1882

Improving TB detection

Quickly and accurately detecting TB, including drug-resistant TB and smear-negative TB (which gives a negative result on sputum smear microscopy), is really important for improving patient outcomes. Many people with TB remain undiagnosed and, although rates are improving, many are not tested for tuberculosis drug resistance. Drug-resistant TB, including multidrug-resistant TB (MDR-TB), defined as resistance to at least isoniazid and rifampicin (anti-TB drugs), is a major problem. People with drug-resistant TB can pass on the infection to others.

Mycobacterial culture, generally considered the best available reference standard (test) for TB diagnosis and the first step in detecting drug resistance, is a fairly complex and slow procedure, needing specialized laboratories and highly skilled staff. The World Health Organization recommends a simple test – Xpert MTB/RIF, and the newest version Xpert Ultra, that within two hours can detect TB and rifampicin resistance in someone with TB symptoms. As well as being quick, the test uses an automated process in a single, self-contained unit, the GeneXpert cartridge, which doesn’t need to be done in a laboratory.

The latest evidence

Two important things to know about a diagnostic test are how sensitive it is – that is, how well it identifies people who have the disease of interest, and how specific – how good it is at identifying those who are free of the disease. A Cochrane Review looking at the diagnostic accuracy of this test previously found Xpert MTB/RIF to be a sensitive and specific test for pulmonary tuberculosis and rifampicin resistance. It has now been updated for a forthcoming WHO policy review. The authors were able to add 77 new studies, bringing the total to 95. 86 studies (42,091 participants) evaluated Xpert MTB/RIF for tuberculosis and 57 studies (8287 participants) for rifampicin resistance. One study compared Xpert MTB/RIF with Xpert Ultra on the same participant specimen. Most studies had low risk of bias. Their findings are consistent with those reported previously.

Key findings

There is high-certainty evidence that Xpert MTB/RIF is sensitive and specific for diagnosing pulmonary TB and rifampicin resistance.

  • Pulmonary TB detection: Xpert MTB/RIF pooled sensitivity and specificity (95% credible Interval (CrI)) were 85% (82% to 88%) and 98% (97% to 98%), (70 studies, 37,237 unselected participants).
  • Rifampicin resistance detection: Xpert MTB/RIF pooled sensitivity and specificity (95% Crl) were 96% (94% to 97%) and 98% (98% to 99%), (48 studies, 8020 participants).

Xpert MTB/RIF is more sensitive for TB in smear-positive than smear-negative people and HIV-negative than HIV-positive people.

  • Xpert MTB/RIF pooled sensitivity was 98% (97% to 98%) in smear‐positive and 67% (62% to 72%) in smear‐negative, culture‐positive participants, (45 studies).
  • Xpert MTB/RIF pooled sensitivity was 88% (83% to 92%) in HIV‐negative and 81% (75% to 86%) in HIV‐positive participants; specificities were similar 98% (97% to 99%), (14 studies).

Compared with Xpert MTB/RIF, Xpert Ultra has higher sensitivity and lower specificity for TB and similar sensitivity and specificity for rifamipicin resistance (one study; moderate-certainty evidence).

  • Xpert Ultra sensitivity (95% confidence interval (CI)) was 88% (85% to 91%) versus Xpert MTB/RIF 83% (79% to 86%). Xpert Ultra specificity was 96% (94% to 97%) versus Xpert MTB/RIF 98% (97% to 99%).
  • Xpert Ultra sensitivity (95% CI) was 95% (90% to 98%) versus Xpert MTB/RIF 95% (91% to 98%); Xpert Ultra specificity was 98% (97% to 99%) versus Xpert MTB/RIF 98% (96% to 99%).

Impact on health outcomes?

Early detection of TB and rifampicin resistance needs to be followed by appropriate treatment for there to be better outcomes for patients.  The review authors could not systematically evaluate the impact of Xpert MTB/RIF on health outcomes in people with TB as part of this review but there is another Cochrane Review under way that is aiming to do this.

Detection of TB and rifampicin resistance in children

A new Cochrane Review Xpert MTB/RIF and Xpert MTB/RIF Ultra assays for active tuberculosis and rifampicin resistance in children has now been published (August 2020).

Special Collection on diagnosing tuberculosis

 Don’t miss this Cochrane Special Collection: Diagnosing tuberculosis, which includes Cochrane Reviews and other systematic reviews, and highlights how Cochrane evidence contributes to the wider landscape of TB evidence and guidelines. The Collection also describes key WHO guidelines on TB diagnostics, and their underpinning systematic reviews.

References (pdf)

This blog was substantially revised on 12 July 2019 and last updated on 28 August 2020.





TB or not TB? That is the question (and here’s the test that can answer it) by Sarah Chapman

is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International

18 Comments on this post

  1. Avatar

    If tb is not detached then past leave granted or not

    Kalyani Joshi / Reply
  2. Avatar

    MTB detected medium and Rifampicin is not detected in age of 65 years old and having stomach highly problem now what to do for treatment please guide and suggest treatment.

    Shuja Ullah / Reply
  3. Avatar

    मेने अपना चेकप कराया था जिसमे डॉक्टर ने बताया कि आपको mtb अब मुझे क्या करना चाहिए और इसके लिए कहा पर दवाई करनी चाहिए क्या इसका इलाज संभव है

    सचिन कुमार / Reply
  4. Avatar

    Mtb detected medium
    Rif resistance not detected
    Tell me what to do

    Ravi Singh / Reply
    • Sarah Chapman

      I’m afraid we can’t give medical advice and you will need to consult your clinician.
      Best wishes,
      Sarah Chapman [Editor]

      Sarah Chapman / (in reply to Ravi Singh) Reply
  5. Avatar

    Mtb not detected means

    Rajat / Reply
  6. Avatar

    MTB not detected in pluemomery water fluied in lungs means wat is the result

    Palani / Reply
  7. Avatar

    Is further any test is needed…if my cbnaat test is positive and rifampicin resistant…I am taking short drug regimen therapy currently..is cbnaat confirms that my sputum is only rifampicin resistant..nd not resistant to any other drug..like isoniazid and moxifloxaCin

    Aaa / Reply
  8. Avatar

    If mtb detected and refampicin is not detected is this dangerus??

    Faiz md / Reply
  9. Avatar

    If my doctors made mistakes it seems obvious now that the last thing they want is for me to ‘get at’ one of the latest tests.
    How does one reverse this atrocious conspiracy? Latent TB positive by Quantiferon gold test paid for privately 2016.
    Past history not looked at 1978 confirmed previous tubercular infection……. 1990 clavical lymphadenopathy. 2013 mesenteric lymphadenopathy…. plenty of adverse symptoms in other areas ignored……… What should transpire now…..
    What is happening is a fob off.

    Michael Hall / Reply
  10. Avatar

    In reports
    Mtb detected high.
    Rif resistance also detected.
    Explain me what to do..

    Vipul / Reply
    • Sarah Chapman

      This is something you’d need to discuss with your clinician.
      Best wishes,
      Sarah [Editor]

      Sarah Chapman / (in reply to Vipul) Reply
  11. Avatar

    can you explain to me i got results negative in TB CBNAAT test and AFB test and more over Chest X ray also normal then what will i get result in TB Sputum Culture test
    Note: 1.TST skin test i got result positive(11mm size)
    2. i dont have any TB symptoms now( like fever,cough, weight lose, food)
    3. i was Latent TB patient (11years back)

    Ramanjaneyulu / Reply
  12. Avatar

    Can you explain to me what is MTB not detected but the xray said its PTB.. thank you

    Jhing dondonayos / Reply
  13. Avatar

    Reblogged this on Soumyadeep B.

    Soumyadeep B / Reply

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