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==Other Diagnostic Studies==
Because of difficulties with the Tuberculin skin test, many laboratory methods of diagnosis are emerging <ref name="pmid12614730">{{cite journal |author=Drobniewski F, Caws M, Gibson A, Young D |title=Modern laboratory diagnosis of tuberculosis |journal=Lancet Infect Dis |volume=3 |issue=3 |pages=141-7 |year=2003 |id=PMID 12614730}}</REF> <REF NAME="pmid17266837">{{cite journal |author=Dinnes J, Deeks J, Kunst H, Gibson A, Cummins E, Waugh N, Drobniewski F, Lalvani A |title=A systematic review of rapid diagnostic tests for the detection of tuberculosis infection |journal=Health Technol Assess |volume=11 |issue=3 |pages=1-314 |year=2007 |id=PMID 17266837 | url = http://www.hta.nhsweb.nhs.uk/project/1247.asp}}</ref>.
 
===Adenosine Deaminase===
In 2007, a systematic review of [[adenosine deaminase]] by the [[NHS]] Health Technology Assessment Programme concluded, "There is no evidence to support the use of ADA tests for the diagnosis of pulmonary TB. However, there is considerable evidence to support their use in pleural fluid samples for diagnosis of pleural TB, where sensitivity was very high, and to a slightly lesser extent for TB meningitis. In both pleural TB and TB meningitis, ADA tests had higher sensitivity than any other tests."<ref name="pmid17266837"/>
 
===Nucleic Acid Amplification Tests (NAAT)===
This is a heterogeneous group of tests that use polymerase chain reaction (PCR) to detect mycobacterial nucleic acid. These test vary in which nucleic acid sequence they detect and vary in their accuracy. The two most common commercially available tests are the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor (Roche Diagnostics). In 2007, a systematic review of NAAT by the [[NHS]] Health Technology Assessment Programme concluded that "NAAT test accuracy to be far superior when applied to respiratory samples as opposed to other specimens. Although the results were not statistically significant, the AMTD test appears to perform better than other currently available commercial tests."<ref name="pmid17266837"/>
 
===Interferon-γ Release Assays===
Interferon-γ (interferon-gamma) release assays (IGRAs) are based on the ability of the ''mycobacterium tuberculosis'' [[antigen]]s for early secretory antigen target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) to stimulate host production of interferon-gamma. Because these antigens are not present in non-tuberculous mycobacteria or in BCG vaccine, these tests can distinguish latent tuberculosis infection (LTBI).
 
The blood tests [[QuantiFERON-TB Gold]] and [[T-SPOT.TB]] use these antigens to detect people with tuberculosis. [[Lymphocyte]]s from the patient's blood are cultured with the antigens. These tests are called [[interferon γ test]]s and are not equivalent.<ref name="Ferrara2006">{{cite journal | author=Ferrara G ''et al.'' | title=Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study | journal=Lancet | volume=367 | issue=9519 | pages=1328&ndash;1334 | id=PMID 16631911 | url=http://www.thelancet.com/journals/lancet/article/PIIS0140673606685796/abstract }}</ref>  If the patient has been exposed to tuberculosis before, [[T cell|T lymphocytes]] produce [[interferon]] γ in response. Both tests use [[ELISA]] to detect the interferon γ with great sensitivity.  The distinction between the tests is that QuantiFERON-TB Gold quantifies the total amount of interferon γ when whole blood is exposed to the antigens, whereas [[T-SPOT.TB]], a type of [[ELISPOT]] assay,<ref>{{cite web|url=http://www.oxfordimmunotec.com/products_services/howtbworks.html|title=How T-SPOT.TB Works}}</ref> counts the number of activated T lymphocytes that secrete interferon γ.  [http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5415a4.htm Guidelines] for the use of the FDA approved QuantiFERON-TB Gold were released by the CDC in December 2005.
   
The enzyme-linked immunospot assay (ELISPOT) is another blood test available in the UK that may replace the skin test for diagnosis <ref name="pmid11438135">{{cite journal |author=Lalvani A, Pathan A, Durkan H, Wilkinson K, Whelan A, Deeks J, Reece W, Latif M, Pasvol G, Hill A |title=Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells |journal=Lancet |volume=357 |issue=9273 |pages=2017-21 |year=2001 |id=PMID 11438135}}</REF> <REF NAME="pmid14586040">{{cite journal |author=Lalvani A |title=Spotting latent infection: the path to better tuberculosis control |journal=Thorax |volume=58 |issue=11 |pages=916-8 |year=2003 |id=PMID 14586040}}</REF> <REF NAME="pmid12686038">{{cite journal |author=Ewer K, Deeks J, Alvarez L, Bryant G, Waller S, Andersen P, Monk P, Lalvani A |title=Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak |journal=Lancet |volume=361 |issue=9364 |pages=1168-73 |year=2003 |id=PMID 12686038}}</ref>.
 
In 2007, two systematic reviews of IGRAs concluded the tests noted excellent specificity and the ability fo the tests to distinguish latent TB from prior vaccination.<ref name="pmid17339619">{{cite journal |author=Menzies D, Pai M, Comstock G |title=Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research |journal=Ann. Intern. Med. |volume=146 |issue=5 |pages=340-54 |year=2007 |pmid=17339619 |doi=}}</ref><ref name="pmid17266837"/>


==References==
==References==
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Other Diagnostic Studies

Because of difficulties with the Tuberculin skin test, many laboratory methods of diagnosis are emerging [1] [2].

Adenosine Deaminase

In 2007, a systematic review of adenosine deaminase by the NHS Health Technology Assessment Programme concluded, "There is no evidence to support the use of ADA tests for the diagnosis of pulmonary TB. However, there is considerable evidence to support their use in pleural fluid samples for diagnosis of pleural TB, where sensitivity was very high, and to a slightly lesser extent for TB meningitis. In both pleural TB and TB meningitis, ADA tests had higher sensitivity than any other tests."[2]

Nucleic Acid Amplification Tests (NAAT)

This is a heterogeneous group of tests that use polymerase chain reaction (PCR) to detect mycobacterial nucleic acid. These test vary in which nucleic acid sequence they detect and vary in their accuracy. The two most common commercially available tests are the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor (Roche Diagnostics). In 2007, a systematic review of NAAT by the NHS Health Technology Assessment Programme concluded that "NAAT test accuracy to be far superior when applied to respiratory samples as opposed to other specimens. Although the results were not statistically significant, the AMTD test appears to perform better than other currently available commercial tests."[2]

Interferon-γ Release Assays

Interferon-γ (interferon-gamma) release assays (IGRAs) are based on the ability of the mycobacterium tuberculosis antigens for early secretory antigen target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) to stimulate host production of interferon-gamma. Because these antigens are not present in non-tuberculous mycobacteria or in BCG vaccine, these tests can distinguish latent tuberculosis infection (LTBI).

The blood tests QuantiFERON-TB Gold and T-SPOT.TB use these antigens to detect people with tuberculosis. Lymphocytes from the patient's blood are cultured with the antigens. These tests are called interferon γ tests and are not equivalent.[3] If the patient has been exposed to tuberculosis before, T lymphocytes produce interferon γ in response. Both tests use ELISA to detect the interferon γ with great sensitivity. The distinction between the tests is that QuantiFERON-TB Gold quantifies the total amount of interferon γ when whole blood is exposed to the antigens, whereas T-SPOT.TB, a type of ELISPOT assay,[4] counts the number of activated T lymphocytes that secrete interferon γ. Guidelines for the use of the FDA approved QuantiFERON-TB Gold were released by the CDC in December 2005.

The enzyme-linked immunospot assay (ELISPOT) is another blood test available in the UK that may replace the skin test for diagnosis [5] [6] [7].

In 2007, two systematic reviews of IGRAs concluded the tests noted excellent specificity and the ability fo the tests to distinguish latent TB from prior vaccination.[8][2]

References

  1. Drobniewski F, Caws M, Gibson A, Young D (2003). "Modern laboratory diagnosis of tuberculosis". Lancet Infect Dis. 3 (3): 141–7. PMID 12614730.
  2. 2.0 2.1 2.2 2.3 Dinnes J, Deeks J, Kunst H, Gibson A, Cummins E, Waugh N, Drobniewski F, Lalvani A (2007). "A systematic review of rapid diagnostic tests for the detection of tuberculosis infection". Health Technol Assess. 11 (3): 1–314. PMID 17266837.
  3. Ferrara G; et al. "Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study". Lancet. 367 (9519): 1328&ndash, 1334. PMID 16631911.
  4. "How T-SPOT.TB Works".
  5. Lalvani A, Pathan A, Durkan H, Wilkinson K, Whelan A, Deeks J, Reece W, Latif M, Pasvol G, Hill A (2001). "Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells". Lancet. 357 (9273): 2017–21. PMID 11438135.
  6. Lalvani A (2003). "Spotting latent infection: the path to better tuberculosis control". Thorax. 58 (11): 916–8. PMID 14586040.
  7. Ewer K, Deeks J, Alvarez L, Bryant G, Waller S, Andersen P, Monk P, Lalvani A (2003). "Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak". Lancet. 361 (9364): 1168–73. PMID 12686038.
  8. Menzies D, Pai M, Comstock G (2007). "Meta-analysis: new tests for the diagnosis of latent tuberculosis infection: areas of uncertainty and recommendations for research". Ann. Intern. Med. 146 (5): 340–54. PMID 17339619.