Published ahead of print on June 23, 2006, doi:10.1164/rccm.200509-1516PP
Am. J. Respir. Crit. Care Med., Volume 174, Number 7, October 2006, 736-742
A more recent version of this article appeared on October 1, 2006
Submitted on September 28, 2005
Accepted on June 16, 2006
An Update on the Diagnosis of Tuberculosis Infection
Luca Richeldi1*
1 Department of Oncology, Haematology and Respiratory Disease, University of Modena and Reggio Emilia, Modena, Italy
* To whom correspondence should be addressed. E-mail: richeldi.luca{at}unimore.it.
Targeted testing and treatment of individuals with latent tuberculosis infection at increased risk of progression to active disease is a key element of tuberculosis control. This strategy is limited by the poor specificity of the tuberculin skin test in BCG-vaccinated populations and its low sensitivity in immunosuppressed persons, who are at highest risk of progression. Two blood tests (T-SPOT.TB and QuantiFERON-TB Gold), based upon detection of interferon- released by T-cells in response to M. tuberculosis-specific antigens, may offer an improvement on the skin test. However, validation is challenging due to the lack of a diagnostic gold standard. This critical appraisal of published evidence summarizes the diagnostic accuracy of the new tests. The blood tests have clear operational advantages over the skin test because no return visit is required, results are available by the next day and repeated testing does not cause boosting. Both tests are significantly more specific than the skin test in BCG-vaccinated populations. The data available suggest that T-SPOT.TB may also be more sensitive than the skin test. Data in groups at high risk of progression to disease are scarce and more research is needed in these populations, but it is already clear that T-SPOT.TB performs better than the skin test in young children and HIV-infected people with active tuberculosis. Incorporation of these tests into programs for targeted testing of latent tuberculosis infection will reduce false-positive and false-negative results inherent in tuberculin testing, equipping clinicians with more accurate tools for tuberculosis control and elimination in the 21st century.
Key words: tuberculosis, diagnosis, interferon- , blood test
This article has been cited by other articles:

|
 |

|
 |
 
A. Lalvani and M. Pareek
A 100 year update on diagnosis of tuberculosis infection
Br. Med. Bull.,
November 18, 2009;
(2009)
ldp039v1.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
U. Sester, H. Wilkens, K. van Bentum, M. Singh, G. W. Sybrecht, H-J. Schafers, and M. Sester
Impaired detection of Mycobacterium tuberculosis immunity in patients using high levels of immunosuppressive drugs
Eur. Respir. J.,
September 1, 2009;
34(3):
702 - 710.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Richeldi
Diagnosing Latent Tuberculosis Infection: Guess Who's Coming to Dinner?
Am. J. Respir. Crit. Care Med.,
July 1, 2009;
180(1):
1 - 2.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Richeldi, M. Losi, R. D'Amico, M. Luppi, A. Ferrari, C. Mussini, M. Codeluppi, S. Cocchi, F. Prati, V. Paci, et al.
Performance of Tests for Latent Tuberculosis in Different Groups of Immunocompromised Patients
Chest,
July 1, 2009;
136(1):
198 - 204.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. N. van Zyl-Smit, M. Pai, K. Peprah, R. Meldau, J. Kieck, J. Juritz, M. Badri, A. Zumla, L. A. Sechi, E. D. Bateman, et al.
Within-Subject Variability and Boosting of T-Cell Interferon-{gamma} Responses after Tuberculin Skin Testing
Am. J. Respir. Crit. Care Med.,
July 1, 2009;
180(1):
49 - 58.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. N. MALAVIYA, S. KAPOOR, S. GARG, R. RAWAT, S. SHANKAR, S. NAGPAL, D. KHANNA, and D. E. FURST
Preventing Tuberculosis Flare in Patients with Inflammatory Rheumatic Diseases Receiving Tumor Necrosis Factor-{alpha} Inhibitors in India -- An Audit Report
J Rheumatol,
July 1, 2009;
36(7):
1414 - 1420.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Blasi, R. Cosentini, G. B. Migliori, and W. Boersma
Steps forward in LRTI and tuberculosis: update from the ERS Respiratory Infections Assembly
Eur. Respir. J.,
June 1, 2009;
33(6):
1448 - 1453.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Diel, R. Loddenkemper, K. Meywald-Walter, R. Gottschalk, and A. Nienhaus
Comparative Performance of Tuberculin Skin Test, QuantiFERON-TB-Gold In Tube Assay, and T-Spot.TB Test in Contact Investigations for Tuberculosis
Chest,
April 1, 2009;
135(4):
1010 - 1018.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. M. BEHAR, D. S. SHIN, A. MAIER, J. COBLYN, S. HELFGOTT, and M. E. WEINBLATT
Use of the T-SPOT.TB Assay to Detect Latent Tuberculosis Infection Among Rheumatic Disease Patients on Immunosuppressive Therapy
J Rheumatol,
March 1, 2009;
36(3):
546 - 551.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. M. Bergamini, M. Losi, F. Vaienti, R. D'Amico, B. Meccugni, M. Meacci, D. De Giovanni, F. Rumpianesi, L. M. Fabbri, F. Balli, et al.
Performance of Commercial Blood Tests for the Diagnosis of Latent Tuberculosis Infection in Children and Adolescents
Pediatrics,
March 1, 2009;
123(3):
e419 - e424.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Bakir, K. A. Millington, A. Soysal, J. J. Deeks, S. Efee, Y. Aslan, D. P.S. Dosanjh, and A. Lalvani
Prognostic Value of a T-Cell-Based, Interferon-{gamma} Biomarker in Children with Tuberculosis Contact
Ann Intern Med,
December 2, 2008;
149(11):
777 - 786.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Lalvani and K. A. Millington
T-cell interferon-{gamma} release assays: can we do better?
Eur. Respir. J.,
December 1, 2008;
32(6):
1428 - 1430.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. L. Anderson, R. J. Welch, and C. M. Litwin
Assessment of Three Commercially Available Serologic Assays for Detection of Antibodies to Mycobacterium tuberculosis and Identification of Active Tuberculosis
Clin. Vaccine Immunol.,
November 1, 2008;
15(11):
1644 - 1649.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Dye and B. G Williams
Eliminating human tuberculosis in the twenty-first century
J R Soc Interface,
June 6, 2008;
5(23):
653 - 662.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. B. E. Chee, S. H. Gan, K. W. KhinMar, T. M. Barkham, C. K. Koh, S. Liang, and Y. T. Wang
Comparison of Sensitivities of Two Commercial Gamma Interferon Release Assays for Pulmonary Tuberculosis
J. Clin. Microbiol.,
June 1, 2008;
46(6):
1935 - 1940.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Strassburg, C. Jafari, M. Ernst, W. Lotz, and C. Lange
Rapid diagnosis of pulmonary TB by BAL enzyme-linked immunospot assay in an immunocompromised host
Eur. Respir. J.,
May 1, 2008;
31(5):
1132 - 1135.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Kobashi, K. Mouri, S. Yagi, Y. Obase, N. Miyashita, N. Okimoto, T. Matsushima, T. Kageoka, and M. Oka
Clinical Utility of the QuantiFERON TB-2G Test for Elderly Patients With Active Tuberculosis
Chest,
May 1, 2008;
133(5):
1196 - 1202.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Beffa, A. Zellweger, J-P. Janssens, P. Wrighton-Smith, and J-P. Zellweger
Indeterminate test results of T-SPOTTM.TB performed under routine field conditions
Eur. Respir. J.,
April 1, 2008;
31(4):
842 - 846.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. P.S. Dosanjh, T. S.C. Hinks, J. A. Innes, J. J. Deeks, G. Pasvol, S. Hackforth, H. Varia, K. A. Millington, R. Gunatheesan, V. Guyot-Revol, et al.
Improved Diagnostic Evaluation of Suspected Tuberculosis
Ann Intern Med,
March 4, 2008;
148(5):
325 - 336.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. C. Leung, W. C. Yam, W. W. Yew, P. L. Ho, C. M. Tam, W. S. Law, M. Y. Wong, M. Leung, and D. Tsui
Comparison of T-Spot.TB and tuberculin skin test among silicotic patients
Eur. Respir. J.,
February 1, 2008;
31(2):
266 - 272.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Jafari, M. Ernst, A. Strassburg, U. Greinert, B. Kalsdorf, D. Kirsten, and C. Lange
Local immunodiagnosis of pulmonary tuberculosis by enzyme-linked immunospot
Eur. Respir. J.,
February 1, 2008;
31(2):
261 - 265.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Palazzo, F. Spensieri, M. Massari, G. Fedele, L. Frasca, S. Carrara, D. Goletti, and C. M. Ausiello
Use of Whole-Blood Samples in In-House Bulk and Single-Cell Antigen-Specific Gamma Interferon Assays for Surveillance of Mycobacterium tuberculosis Infections
Clin. Vaccine Immunol.,
February 1, 2008;
15(2):
327 - 337.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Losi, A. Bossink, L. Codecasa, C. Jafari, M. Ernst, S. Thijsen, D. Cirillo, M. Ferrarese, U. Greinert, L. M. Fabbri, et al.
Use of a T-cell interferon-{gamma} release assay for the diagnosis of tuberculous pleurisy
Eur. Respir. J.,
December 1, 2007;
30(6):
1173 - 1179.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Pratt, K. Nicholl, and L. Kay
Comment on: Use of the QuantiFERON-TB(R) Gold test as part of a screening programme in patients with RA under consideration for treatment with anti-TNF-{alpha} agents: the Newcastle (UK) experience: reply
Rheumatology,
December 1, 2007;
46(12):
1864 - 1865.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. G. Madariaga, Z. Jalali, and S. Swindells
Clinical Utility of Interferon Gamma Assay in the Diagnosis of Tuberculosis
J Am Board Fam Med,
November 1, 2007;
20(6):
540 - 547.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Kobashi, K. Mouri, Y. Obase, M. Fukuda, N. Miyashita, and M. Oka
Clinical evaluation of QuantiFERON TB-2G test for immunocompromised patients
Eur. Respir. J.,
November 1, 2007;
30(5):
945 - 950.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
U. R. Dahle, V. Eldholm, B. A. Winje, T. Mannsaker, and E. Heldal
Impact of Immigration on the Molecular Epidemiology of Mycobacterium tuberculosis in a Low-Incidence Country
Am. J. Respir. Crit. Care Med.,
November 1, 2007;
176(9):
930 - 935.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J-P. Janssens, P. Roux-Lombard, T. Perneger, M. Metzger, R. Vivien, and T. Rochat
Quantitative scoring of an interferon-{gamma} assay for differentiating active from latent tuberculosis
Eur. Respir. J.,
October 1, 2007;
30(4):
722 - 728.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. A. Kang, H. W. Lee, S. S. Hwang, S.-W. Um, S. K. Han, Y.-S. Shim, and J.-J. Yim
Usefulness of Whole-Blood Interferon-{gamma} Assay and Interferon-{gamma} Enzyme-Linked Immunospot Assay in the Diagnosis of Active Pulmonary Tuberculosis
Chest,
September 1, 2007;
132(3):
959 - 965.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. G. Connell, M. S. Shey, R. Seldon, M. X. Rangaka, G. van Cutsem, M. Simsova, Z. Marcekova, P. Sebo, N. Curtis, L. Diwakar, et al.
Enhanced Ex Vivo Stimulation of Mycobacterium tuberculosis-Specific T Cells in Human Immunodeficiency Virus-Infected Persons via Antigen Delivery by the Bordetella pertussis Adenylate Cyclase Vector
Clin. Vaccine Immunol.,
July 1, 2007;
14(7):
847 - 854.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Lalvani
Diagnosing Tuberculosis Infection in the 21st Century: New Tools To Tackle an Old Enemy
Chest,
June 1, 2007;
131(6):
1898 - 1906.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. K. Reid, H. Ward, D. Marciniuk, S. Hudson, P. Smith, and V. Hoeppner
The Effect of Neonatal Bacille Calmette-Guerin Vaccination on Purified Protein Derivative Skin Test Results in Canadian Aboriginal Children
Chest,
June 1, 2007;
131(6):
1806 - 1810.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. J Marais and M. Pai
Recent advances in the diagnosis of childhood tuberculosis
Arch. Dis. Child.,
May 1, 2007;
92(5):
446 - 452.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. X. Rangaka, K. A. Wilkinson, R. Seldon, G. Van Cutsem, G. A. Meintjes, C. Morroni, P. Mouton, L. Diwakar, T. G. Connell, G. Maartens, et al.
Effect of HIV-1 Infection on T-Cell-based and Skin Test Detection of Tuberculosis Infection
Am. J. Respir. Crit. Care Med.,
March 1, 2007;
175(5):
514 - 520.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Richeldi
Should Individuals Who Are Tuberculin Skin Test Negative and Positive to RD1-IFN-{gamma} Assay Receive Preventive Therapy?
Am. J. Respir. Crit. Care Med.,
January 15, 2007;
175(2):
200 - 200.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Girardi, D. Goletti, and G. Ippolito
Should Individuals Who Are Tuberculin Skin Test Negative and Positive to RD1-IFN-{gamma} Assay Receive Preventive Therapy?
Am. J. Respir. Crit. Care Med.,
January 15, 2007;
175(2):
198a - 199.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. J. Radford, J. S. Rothel, S. L. Jones, and G. Sberna
Tuberculosis diagnostic tests: sensitivity, specificity, and comparing apples with apples.
Am. J. Respir. Crit. Care Med.,
October 15, 2006;
174(8):
953 - 953.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Richeldi
Tuberculosis diagnostic tests: sensitivity, specificity, and comparing apples with apples.
Am. J. Respir. Crit. Care Med.,
October 15, 2006;
174(8):
953a - 9954.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. F. Barnes
Weighing gold or counting spots: which is more sensitive to diagnose latent tuberculosis infection?
Am. J. Respir. Crit. Care Med.,
October 1, 2006;
174(7):
731 - 732.
[Full Text]
[PDF]
|
 |
|
Copyright © 2006 American Thoracic Society
|
|
|