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REVIEW ARTICLE
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Role of genexpert or CBNAAT in diagnosing tuberculosis: Present scenario


1 Department of Microbiology, Government Medical College, Kota, Rajasthan, India
2 Department of Pathology, Government Medical College, Kota, Rajasthan, India

Date of Submission14-Apr-2020
Date of Decision18-Jul-2020
Date of Acceptance26-Jul-2020

Correspondence Address:
Lakshmi Agarwal,
Department of Pathology, Government Medical College, Rangbari Road, Kota - 324 010, Rajasthan
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjdrdypu.mjdrdypu_182_20

  Abstract 


About a quarter of the world's population is infected with tuberculosis (TB), with new infection occurring every second. The global burden, particularly with multidrug resistance, is also increasing simultaneously and has become a major health challenge. Earlier and improved case detection, including smear-negative disease, often associated with HIV co-infection, and expanded capacity to diagnose multidrug-resistant TB are global priorities for TB control. Conventional laboratory methods are slow and cumbersome. Hence, novel technologies for rapid detection are the focus of TB research and development. GeneXpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) is one of them, currently unique in its simplification of molecular testing with amplification and detection based on real-time polymerase chain reaction. Xpert MTB/RIF detects MTB as well as RIF resistance directly from sputum within 2 h. This article focuses on the significance of new diagnostic test for TB.

Keywords: Conventional test, GeneXpert, global burden, multidrug resistance



How to cite this URL:
Garg A, Agarwal L, Mathur R. Role of genexpert or CBNAAT in diagnosing tuberculosis: Present scenario. Med J DY Patil Vidyapeeth [Epub ahead of print] [cited 2021 Nov 30]. Available from: https://www.mjdrdypv.org/preprintarticle.asp?id=321287




  Introduction Top


Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), one of the top 10 causes of death worldwide (ranking above HIV/AIDS). About a quarter of the world's population is infected with TB and thus at risk of developing TB disease. The Global TB Report 2019 states that in 2018 a total of 1.5 million people died from TB, an estimated 10 million (range, 9.0–11.1 million) people fell ill worldwide.[1] Eight countries accounted for two-thirds of the total, with India leading the count, followed by China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh, and South Africa.[1]

Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat. The WHO estimates that there were 484 000 new cases with resistance to rifampicin (RIF) – the most effective first-line drug, which accounts for 78% MDR-TB cases. The MDR-TB burden largely falls on three countries – India, China, and the Russian Federation. About 6.2% of MDR-TB cases had extensively drug-resistant TB (XDR-TB) in 2018. Worldwide, only 56% of MDR-TB patients are currently successfully treated. Globally, TB incidence is falling at about 2% per year. This needs to accelerate to a 4%–5% annual decline to reach the 2020 milestones of the End TB Strategy.[1]

TB is curable if it is diagnosed and treated in a timely manner. Therefore, the accurate and rapid detection of TB has a critical role to play in the reduction of disease transmission in the community.

Currently, there are both direct and indirect methods of diagnosis of TB. Direct detection methods include microscopy, culture, antigen detection, and nucleic acid detection. Indirect tests include tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) based on the immune response.

The smear microscopy and conventional culture technique has been the mainstay of diagnostic testing for pulmonary TB. The smear microscopy is cheap, easy to use, specific (specificity: >95%) but has poor sensitivity 25%–65% (90% of infectious cases) since it requires at least 10,000 bacilli per milliliter of sputum and it also depends on the proficiency of the personnel.[2] Smear testing detects approximately half of all cases of active TB, which is less sensitive in HIV-infected patients, extrapulmonary TB patients, and children. As a result, health services miss many TB patients or identify them only when their disease is at an advanced stage. It cannot be used to identify drug resistance and does not differentiate between MTB and nontuberculous mycobacteria (NTM). Conventional solid culture is the most reliable reference standard. However, it takes around 6–8 weeks to grow, and moreover, drug resistance testing requires an additional 3 more weeks.[3] It demands expertise as well as costly infrastructure to ensure sufficient biosafety conditions.

Liquid culture techniques such as BACTEC or mycobacterial growth indicator tube (MGIT) were developed for early detection of TB growth, but the mean turnaround time is 42 days.[4] Apart from this other culture techniques were also developed such as thin layer agar culture, which has an average turnaround time of 11.5 days and microscopic observation drug susceptibility assay, which can provide results in an average of 9.2 days.[6] Phage-based assays give results in 2 days.[7] They are better than smear microscopy, but turnaround times are longer. They also require proper infrastructure and equipment, leading to higher costs per test.

Chest X-ray is neither sensitive nor specific for the diagnosis of TB. The sensitivity of TST and IGRAs is suboptimal, and neither adequately distinguishes latent from active TB. Positive tuberculin test may be negative in active TB.[8] Biochemical tests are nonspecific, and ADA has a more negative prediction value than positive prediction value.[9]

Thus, older laboratory methods are slow and cumbersome leading to delays in diagnosis. This increases morbidity and mortality, predisposes to secondary resistance and cause transmission of resistant strains. Various molecular tests have been developed to overcome the limitations of the above methods. They provide a rapid and reliable diagnosis as the threshold for detection is low 10–100 cfu/ml.[9] It detects MTB in pulmonary and extrapulmonary samples. However, molecular tests too have disadvantages. They are more sensitive than smear but less sensitive than culture. It has a sensitivity of 95% in smear-positive TB and 50%–60% in smear-negative TB compared to culture. The specificity is around 98%.[10] Overall, the test detected 90.7% of culture-positive TB.

A negative nucleic acid amplification (NAA) test result does not always exclude the diagnosis of TB. Specimens may contain inhibitors that prevent amplification to cause false-negative results. False-positive results can be there due to error and can be suspected if a patient has a single positive NAA but little suspicion of active TB.

Similarly, a single negative NAA test result should never be used as a definitive test to exclude TB, especially in suspects with a moderate-to-high clinical suspicion of TB. In both cases, the result should be interpreted with other findings.

Hence, there is an urgent necessity for tests that can quickly diagnose TB and drug resistance. One such development is GeneXpert (CBNAAT).

CBNAAT

In 2013, Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) became the first molecular TB test endorsed by the World Health Organization (WHO).[11] CBNAAT is a totally automated test where the separate cartridge is used for each test and can also be used as a point-of-care test.

It comes in various sizes. The smallest machine has capacity for one cartridge (in other words, one test can be run at a time). The largest has capacity for 100 cartridges.

Samples

Pulmonary specimens such as sputum, tracheal aspirates, induced sputum, bronchoalveolar lavage and extrapulmonary specimens which include all types of fluids (ascitic, pericardial, and pleural fluid), tissues, lymph nodes, pus from abscess, cerebrospinal fluid (CSF), gastric lavage, except stool, urine, and blood.[11]

Storage of sample

Whenever possible, specimens should be transported and stored at 2°C–8°C before processing (the maximum time for storage and processing is 7 days)


  The World Health Organization Recommendations for XPERT Mycobacterium tuberculosis/Rifampicin Assay Top


For diagnosis of pulmonary tuberculosis

  1. May be used as an initial diagnostic test over smear and culture in adults and children with HIV or suspected of having TB or MDR-TB.


For diagnosis of extrapulmonary tuberculosis

  1. It is strongly recommended as an initial diagnostic test of choice over microscopy and culture for CSF specimens from patients suspected of having TB meningitis
  2. Replacement test for testing nonrespiratory specimens (lymph nodes and other tissues and fluids) from patients suspected of having extrapulmonary TB.


Principle

It is a rapid test and simultaneously detects TB and RIF drug resistance within 2 h based on reverse transcription–polymerase chain reaction (PCR). It integrates and automates sample processing, amplification, and detection of target sequences. The primer amplifies a portion of the rpoB gene containing the 81 base pair core regions known as the RIF-resistance-determining region. It covers all the mutations found in >99.5% of all RIF-resistant strains. RIF resistance is considered as a surrogate marker of MDR-TB as around >90% of RIF-resistant bacilli are resistant to INH. Monoresistance to rifampicin (RMP) is rare. Therefore, the detection of RMP resistance may serve as a surrogate marker of MDR-TB.[12],[13]

Procedure

A sample reagent containing NaOH and isopropanol was added at a 2:1 ratio to clinical specimens or on decontaminated specimens. It enables specimens to be cultured concurrently. Tissues must be processed within a biological safety cabinet to avoid the risk of producing aerosols while grinding and homogenizing samples.

The closed specimen is kept at room temperature for 15 min and should be agitated twice. After this, 2 ml of the inactivated material was transferred to the disposable test cartridge. All subsequent steps occur automatically.[14] It detects MTB genomic copies as few as 130–150 cfu/mL[15] Modules function independently, so that batching is not required, and individual tests can be started at different times. Cartridge disposal was done according to local guidelines for hazardous materials, identical to a sputum container.

Results and Interpretation

MTB detected or not RIF resistance detection can be of the following types as high, medium, intermediate, low, or very low.

  1. RIF resistance detected means that the bacteria have a high probability of resistance to RIF. This should be confirmed by additional rapid testing. If RIF resistance is confirmed, rapid molecular testing for drug resistance to both first-line and second-line drugs should be performed
  2. RIF resistance not detected means that the bacteria are susceptible to RIF
  3. RIF resistance indeterminate – It means that the test could not accurately determine if the bacteria are resistant to RIF. For “RIF indeterminate result,” an additional CBNAAT should be done to get a valid result. If the second result is also indeterminate, then an additional specimen should be sent to the nearest intermediate reference laboratory for line tuberculosis probe assay (LPA) or liquid culture and drug susceptibility testing (DST). The rate of indeterminate Xpert MTB/RIF results was 3.7%, lower than the rate of culture contamination, and repeat testing led to a valid result in 97% of patients
  4. Invalid result – Then, the test has to be repeated
  5. For “Error,” “No results” – The test can be repeated on the same specimen after the correction of appropriate troubleshooting.


Mycobacterium tuberculosis not detected but tuberculosis still suspected

Further investigation, such as chest X-ray, culture, and repeat Xpert MTB/RIF, should be done.

Mycobacterium tuberculosis detected rifampicin sensitive

WHO recommends first-line treatment and registration as bacteriologically confirmed TB.

Mycobacterium tuberculosis detected rifampicin resistance.

It includes two groups:

  1. In groups with low risk of multidrug resistant tuberculosis prevalence- Xpert MTB/RIF should be repeated.


    • If the same result is obtained, WHO recommends regimen for MDR TB with isoniazid and registration as rifampicin resistant TB. Further DST should be done for Rifampicin, isoniazid, quinolones, Second line injectable drugs like aminoglycosides which include Amikacin, Kanamycin and Capreomycin. The treatment should be modified accordingly.
    • If repeat result is like MTB detected Rifampicin sensitive, then first line treatment should be started and further testing by phenotypic DST is not required


  2. In groups with high risk of MDR TB, repeat testing is not required.


  • In rare cases where discordant results are obtained from Xpert MTB/RIF and phenotypic DST or LPA, the available culture isolate should be referred to reference laboratory for DNA sequencing.



  Advantage Top


  1. It simultaneously detects MTB and resistance to rifampin in less than 2 h in contrast to solid LJ media which takes up to 84 days, liquid culture (MGIT) take 42 days and , LPA takes up to 2 days In the same way, loop-mediated isothermal amplification (LAMP) which is used as an alternative to smear microscopy has a similar sensitivity and specificity to Xpert MTB/RIF, but it is unable to detect RIF-resistant. It has been evaluated only in sputum specimens. Its use with other samples (e. g., urine, serum, plasma, cerebrospinal fluid, or other body fluids) has not been adequately evaluated
  2. Hence, Xpert/Gene enables early and appropriate treatment initiation, as well as accelerating the implementation of MDR-TB control measures compared to other methods. This influences a variety of management decisions such as earlier treatment initiation, better patient care and outcomes, greater opportunities to interrupt transmission, and improved public health intervention
  3. It is suitable for use at district and subdistrict level, where biological safety cabinets are usually not available in laboratories as the infrastructure requirements for the Xpert MTB/RIF assay are the same as for smear microscopy
  4. It also does not require high expertise because of a very simple software-based reporting system. While other molecular tests need infrastructure and investment requirements for DNA extraction, amplification and detection, and the biosafety concerns that are often beyond the scope of most diagnostic facilities. They cannot be used as point-of-care tests. Their results also vary widely from laboratory to laboratory[16]
  5. The reagents used for treatment of samples has mycobactericidal activity. It kills about 99.99% of TB bacilli. As a result, aerosolization of mycobacteria doesn't occur while running the device.
  6. There is no cross-reactivity with NTM and TB and RIF resistance correctly detected in the presence of nontuberculous DNA or a mix of susceptible strains and resistant strains
  7. The use of Xpert MTB-RIF significantly increased TB case finding (by roughly 30%) when used as a replacement or add-on test to microscopy. Its use as a replacement for conventional culture and DST also significantly increased multidrug resistance case finding (roughly threefold)
  8. HIV co-infection substantially decreased the sensitivity of microscopy to 47%. Commonly used molecular test LPA is recommended only in smear-positive cases, so it is less sensitive in HIV and extrapulmonary TB, while MTB/RIF Xpert did not significantly affect the performance in such cases
  9. It has a high sensitivity of 95.7% and specificity of 99.3% for detecting MTB in pulmonary samples. The sensitivity for detecting smear-negative culture-positive samples was 77.7% with a single test. It increases to 90.2% when three samples are tested. The sensitivity for single GeneXpert in detecting smear-positive culture-positive samples was 99.2%; in comparison, the sensitivity of a single direct smear test was 59.5% in culture-positive cases. As specificity is very high, so false-positive results are likely to be due to dead MTB bacilli that would not be detected by culture
  10. The sensitivity and specificity for detecting RIF resistance were 94.5% and 97.7%, respectively, with respect to culture as a reference standard.[17] The negative predictive value is around 98% both in settings with a low prevalence and high prevalence of RIF resistance, which means that a negative result accurately excludes the possibility of RIF resistance, and usually, no further testing is required for confirmation.[18] In rare instances, when a patient is strongly suspected of having MDR-TB even after a negative result that may be due to resistance develop outside of the rpoB region, a follow-up test may be done using phenotypic culture-based DST
  11. The positive predictive value (PPV) for RIF resistance exceeds 90% in settings where the underlying prevalence of RIF resistance is >15%. It ranges between 71% and 84%, where the prevalence of RIF resistance is between 5% and 10%, and diminishes further to <70% when the prevalence of RIF resistance falls below 5%. In such circumstances, positive Xpert MTB/RIF results should be confirmed by conventional DST or LPA and risk assessment[18]
  12. The sensitivity of CBNAAT, when compared to liquid culture is high for extrapulmonary specimens. It is 84.9% for lymph node and 81.2% for other tissue. The gastric fluid 83.8%, and CSF 79.5% and still lower in pleural fluid 43.7%. A pleural biopsy provides the preferred specimen.[18] Data on the utility of Xpert MTB/RIF in extrapulmonary specimens are still limited
  13. The use of Xpert MTB/RIF on all smear-positive samples should help to rapidly identify samples with NTM
  14. All specimens should be processed as soon as possible for optimal culture recovery of MTB though longer transportation times of specimens do not affect the use of Xpert MTB/RIF
  15. The same system can be used for other conditions such as early infant HIV diagnosis and viral load monitoring (pending WHO approval)
  16. DNA contamination events were not recorded, despite 50% of operators not having followed instructions to clean instrument surfaces with bleach and ethanol on a daily basis.[16]



  Disadvantages Top


  1. GeneXpert is more expensive than the standard sputum smear tests though similar to the cost for performing culture and DST
  2. It requires an uninterrupted supply of electricity, annual calibration, and operating temperatures 15°C–30°C. The machine needs to be connected to a computer. The cartridges require adequate storage space and have a shelf life of 18 months. Stable if kept at 2°C–45°C for <6 weeks at 75% relative humidity. The cartridge should be used within 4 h after opening the cartridge lid[11]
  3. Xpert cannot be used for assessing the emergence of RIF resistance during treatment. The currently available tests for rpoB mutations detect majority but not all cases of RIF resistance. In settings where RIF resistance is rare, Xpert MTB/RIF results should be confirmed by conventional DST or LPA
  4. It is not suitable to detect resistance other than RIF[15],[19] and does not eliminate the need for conventional microscopy culture and universal DST (UDST). UDST is required to monitor the progress of treatment and to detect resistance other than RIF like XDR-TB and isoniazid mono-resistance and in discordant situation
  5. The test remains positive even after appropriate therapy since it detects DNA from both viable and nonviable bacilli like other molecular tests[11]
  6. Given that the specificity of Xpert MTB/RIF is not 100%, the PPV of Xpert MTB/RIF testing is adversely affected in settings with a low prevalence of disease
  7. A positive CBNAAT provides useful confirmation, but a negative test does not always rule out TB. Patients with a negative GeneXpert can still have TB with MTB or mycobacteria other than tuberculosis species and should undergo further diagnostic testing, and as with other NAA tests, it should be interpreted along with clinical, radiographic, and other laboratory findings.



  Newer Developments Top


  1. In 2017, the Xpert Ultra assay was developed by Cepheid as the next-generation assay. It has improved the sensitivity and detection of resistance to RIF in smear-negative and HIV-associated TB in which Xpert MTB/RIF sensitivity is imperfect. To improve assay sensitivity for the detection of MTB, it incorporates two different multicopy amplification targets (IS6110 and IS1081) and a larger DNA reaction chamber than Xpert MTB/RIF (50 μl PCR reaction in Ultra versus 25 μl in Xpert MTB/RIF). Ultra also incorporates fully nested nucleic acid amplification, more rapid thermal cycling, and improved fluidics and enzymes. This has resulted in Ultra having a limit of detection of 16 bacterial colony-forming units (cfu) per milliliter (compared to 114 cfu per ml for Xpert MTB/RIF). To improve the accuracy of RIF resistance detection, the Ultra incorporates melting temperature-based analysis instead of real-time PCR. It uses the same semi-quantitative categories as in the Xpert MTB/RIF assay (high, medium, low, and very low) as well as the addition of a new category “trace” that corresponds to the lowest bacillary burden for MTB detection. For EPTB and pediatric TB, there is a benefit of the increased sensitivity with a sensitivity of 95% for Ultra versus 45% for Xpert MTB/RIF for detection of TB meningitis using cerebrospinal fluid and 71% for Ultra on respiratory samples from children versus 47% for Xpert MTB/RIF
  2. A new device called the GeneXpert Omni is currently under development. It is intended for point-of-care testing for TB and RIF resistance, using the same cartridges. It is expected to be smaller, lighter, and less expensive than the current GeneXpert. It can use battery or solar power and can withstand dust and heat and is expected to have fewer training requirements
  3. TrueNat – This is a new molecular test using the PCR technique which can diagnose TB in 1 h as well as resistance to RIF. It takes about 1 h to diagnose TB and an additional 1 h for RIF resistance testing. It showed comparable accuracy to GeneXpert and, also with line probe assays, TB-LAMP assay as replacement tests for sputum smear microscopy

    Only about 0.5 ml of the sample is required to compare 1 ml in GeneXpert. It can be used at the most basic part of the health-care system since the entire setup is battery operated and portable. It has been endorsed by the WHO in January 2020. However, the TrueNat test and CB-NAAT (GeneXpert) are designed to be used in different circumstances.[17]
  4. New Xpert® MTB/XDR* test – In July 2020, Cepheid and FIND developed this test which could detect resistance to both first-line and second-line drugs. It can find resistance in 90 min and correct treatment for both MDR-TB and XDR-TB. It can detect resistance to isoniazid, ethionamide, fluoroquinolones, amikacin, kanamycin, and capreomycin by analyzing multiple mutations across several genes. Thus, it helps clinicians in changing treatment protocol.[20]



  Conclusion Top


TB is curable if it is treated in a timely manner, so the accurate and rapid detection of TB has a critical role to play in the prevention and treatment. Regardless of all these limitations, Xpert MTB/RIF remains a very valuable tool because of its unambiguous, rapid results, and high sensitivity and specificity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
World Health Organization (2019). Global tuberculosis report 2019. https://apps.who.int/iris/handle/10665/329368.  Back to cited text no. 1
    
2.
Chang K, Lu W, Wang J, Zhang K, Jia S, Li F, et al. Rapid and effective diagnosis of tuberculosis and rifampicin resistance with Xpert MTB/RIF assay: A meta-analysis. J Infect 2012;64:580-8.  Back to cited text no. 2
    
3.
Steingart KR. Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev 2014;2014:CD009593.  Back to cited text no. 3
    
4.
Moore DF, Guzman JA, Mikhail LT. Reduction in turnaround time for laboratory diagnosis of pulmonary tuberculosis by routine use of a nucleic acid amplification test. Diagn Microbiol Infect Dis 2005;52:247-54.  Back to cited text no. 4
    
5.
Cattamanchi A, Davis JL, Worodria W, den Boon S, Yoo S, Matovu J, et al. Sensitivity and specificity of fluorescence microscopy for diagnosing pulmonary tuberculosis in a high HIV prevalence setting. Int J Tuberc Lung Dis 2009;13:1130-6.  Back to cited text no. 5
    
6.
Hung NV, Sy DN, Anthony RM, Cobelens FG, van Soolingen D. Fluorescence microscopy for tuberculosis diagnosis. Lancet Infect Dis 2007;7:238-9.  Back to cited text no. 6
    
7.
Balabanova Y, Drobniewski F, Nikolayevskyy V, Kruuner A, Malomanova N, Simak T, et al. An integrated approach to rapid diagnosis of tuberculosis and multidrug resistance using liquid culture and molecular methods in Russia. PLoS One 2009;4:e7129.  Back to cited text no. 7
    
8.
Pai M, Denkinger CM, Kik SV, Rangaka MX, Zwerling A, Oxlade O, et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev 2014;27:3-20.  Back to cited text no. 8
    
9.
Wiener RS, Della-Latta P, Schluger NW. Effect of nucleic acid amplification for Mycobacterium tuberculosis on clinical decision making in suspected extrapulmonarytuberculosis. Chest 2005;128:102.  Back to cited text no. 9
    
10.
Della-Latta P, Whittier S. Comprehensive evaluation of performance, laboratory application, and clinical usefulness of two direct amplification technologies for the detection of Mycobacterium tuberculosis complex. Am J Clin Pathol 1998;110:301-10.  Back to cited text no. 10
    
11.
World Health Organisation (WHO). Xpert MTB/RIF Implementation Manual. Technical and Operational 'How-to': Practical Considerations; 2014. Available from: http://apps.who.int/iris/bitstream/10665/112469/1/9789241506700_eng.pdf. [Last accessed on 2015 Nov 4].  Back to cited text no. 11
    
12.
Blakemore R, Story E, Helb D, Kop J, Banada P, Owens MR, et al. Evaluation of the analytical performance of the Xpert MTB/RIF assay. J Clin Microbiol 2010;48:2495-501.  Back to cited text no. 12
    
13.
Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med 2010;363:1005-15.  Back to cited text no. 13
    
14.
Xpert MTB RIF kit insert. Available from: http://www. cepheid.com/manageddownloads/xpertmtb-rif-english-package-insert- 301-1404-rev-b-february-2015.pdf. [Last accessed on 2015 Dec 17].  Back to cited text no. 14
    
15.
Sharma SK, Kohli M, Yadav RN, Chaubey J, Bhasin D, Sreenivas V, et al. Evaluating the diagnostic accuracy of Xpert MTB/RIF assay in pulmonary tuberculosis. PLoS One 2015;10:e0141011.  Back to cited text no. 15
    
16.
Policy Statement: Automated Real-time Nucleic Acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF System, WHO; 2011.  Back to cited text no. 16
    
17.
True Nat TB Test. Available from: https://www tbfact.org.[Last accessed on 2016 Jul 29].  Back to cited text no. 17
    
18.
Xpert MTB/RIF Implementation Manual WHO; 2014. [Last accessed on 2018 Dec 22].  Back to cited text no. 18
    
19.
World health Organisation (WHO). Global Tuberculosis Report; 2016. Available from: http://apps.who.int/iris/bitstream/10665/25044/1/9789241565394-eng.pdf.  Back to cited text no. 19
    
20.
World Health Organization. Drug Resistance TB: XDR-TB FAQ. Available from: https://www.who.int/tb/ares-of-work/drug- resistance-tb/xdr-tb faq/en/.[Last accessed on 2020 May 15].  Back to cited text no. 20
    




 

 
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