Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2010

Open Access 01-12-2010 | Research article

IFN-γ response on T-cell based assays in HIV-infected patients for detection of tuberculosis infection

Authors: Irene Latorre, Xavier Martínez-Lacasa, Roser Font, Alicia Lacoma, Jordi Puig, Cristina Tural, Josep Lite, Cristina Prat, Eva Cuchi, Vicente Ausina, Jose Domínguez

Published in: BMC Infectious Diseases | Issue 1/2010

Login to get access

Abstract

Background

Individuals infected with human immunodeficiency virus (HIV) have an increased risk of progression to active tuberculosis following Mycobacterium tuberculosis infection. The objective of the study was to determine IFN-γ responses for the detection of latent tuberculosis infection (LTBI) with QuantiFERON-TB GOLD In Tube (QFT-G-IT) and T-SPOT.TB in HIV patients, and evaluate the influence of CD4 cell count on tests performance.

Methods

We studied 75 HIV patients enrolled for ongoing studies of LTBI with T-SPOT.TB, QFN-G-IT and TST. Mean CD4 cell counts ± standard deviation was 461.29 ± 307.49 cells/μl. Eight patients had a BCG scar.

Results

T-SPOT.TB, QFN-G-IT and TST were positive in 7 (9.3%), 5 (6.7%) and 9 (12%) cases, respectively. Global agreement between QFN-G-IT and T-SPOT.TB was 89% (κ = 0.275). The overall agreement of T-SPOT.TB and QFN-G-IT with TST was 80.8% (κ = 0.019) and 89% (κ = 0.373), respectively. We have found negative IFN-γ assays results among 2 BCG-vaccinated HIV-infected individuals with a positive TST. In non BCG-vaccinated patients, QFN-G-IT and TST were positive in 5 cases (7.5%) and T-SPOT.TB in 7 (10.4%). In contrast, in BCG-vaccinated patients, only TST was positive in 4/8 (50%) of the cases. The differences obtained in the number of positive results between TST and both IFN-γ assays in BCG vaccinated patients were significant (95% CI 3-97%, p = 0.046), however, the confidence interval is very wide given the small number of patients. In patients with CD4< 200, we obtained only one (5%) positive result with T-SPOT.TB; however, QFN-G-IT and TST were negative in all cases. On the contrary, percentages of positive results in patients with CD4> 200 were 10.9% (6/55), 9.1% (5/55) and 16.4% (9/55) with T-SPOT.TB, QFN-G-IT and TST, respectively.

Conclusions

IFN-γ tests have the benefit over TST that are less influenced by BCG vaccination, consequently they are more specific than TST. Although our number of patients with advance immunosuppression is limited, our study suggests that IFN-γ assays are influenced with level of immunosuppression. The use of IFN-γ assays could be a helpful method for diagnosing LTBI in HIV population.
Appendix
Available only for authorised users
Literature
1.
World Health Organization: Global Tuberculosis Control - Surveillance, Planning, Financing (WHO/HTN/TB/2005.349). Geneva, Switzerland. 2005
2.
Corbett EL, Charalambous S, Moloi VM, Fielding K, Grant AD, Dye C, De Cock KM, Hayes RJ, Williams BG, Churchyard GJ: Human immunodeficiency virus and the prevalence of undiagnosed tuberculosis in African gold miners. Am J Respir Crit Care Med. 2004, 170: 673-679. 10.1164/rccm.200405-590OC.CrossRefPubMed
3.
Jasmer RM, Nahid P, Hopewell PC: Clinical practice. Latent tuberculosis infection. N Engl J Med. 2002, 347: 1860-1866. 10.1056/NEJMcp021045.CrossRefPubMed
4.
5.
Selwyn PA, Sckell BM, Alcabes P, Friedland GH, Klein RS, Schoenbaum EE: High risk of active tuberculosis in HIV-infected drug users with cutaneous anergy. Jama. 1992, 268: 504-509. 10.1001/jama.268.4.504.CrossRefPubMed
6.
Andersen P, Munk ME, Pollock JM, Doherty TM: Specific immune-based diagnosis of tuberculosis. Lancet. 2000, 356: 1099-1104. 10.1016/S0140-6736(00)02742-2.CrossRefPubMed
7.
Brock I, Weldingh K, Leyten EM, Arend SM, Ravn P, Andersen P: Specific T-cell epitopes for immunoassay-based diagnosis of Mycobacterium tuberculosis infection. J Clin Microbiol. 2004, 42: 2379-2387. 10.1128/JCM.42.6.2379-2387.2004.CrossRefPubMedPubMedCentral
8.
Dominguez J, Ruiz-Manzano J, De Souza-Galvao M, Latorre I, Mila C, Blanco S, Jimenez MA, Prat C, Lacoma A, Altet N, Ausina V: Comparison of two commercially available gamma interferon blood tests for immunodiagnosis of tuberculosis. Clin Vaccine Immunol. 2008, 15: 168-171. 10.1128/CVI.00364-07.CrossRefPubMed
9.
Lalvani A, Pathan AA, Durkan H, Wilkinson KA, Whelan A, Deeks JJ, Reece WH, Latif M, Pasvol G, Hill AV: Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Lancet. 2001, 357: 2017-2021. 10.1016/S0140-6736(00)05115-1.CrossRefPubMed
10.
Ferrara G, Losi M, D'Amico R, Roversi P, Piro R, Meacci M, Meccugni B, Dori IM, Andreani A, Bergamini BM, et al: Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study. Lancet. 2006, 367: 1328-1334. 10.1016/S0140-6736(06)68579-6.CrossRefPubMed
11.
Ewer K, Deeks J, Alvarez L, Bryant G, Waller S, Andersen P, Monk P, Lalvani A: Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak. Lancet. 2003, 361: 1168-1173. 10.1016/S0140-6736(03)12950-9.CrossRefPubMed
12.
Richeldi L: An update on the diagnosis of tuberculosis infection. Am J Respir Crit Care Med. 2006, 174: 736-742. 10.1164/rccm.200509-1516PP.CrossRefPubMed
13.
Casas I, Latorre I, Esteve M, Ruiz-Manzano J, Rodriguez D, Prat C, Garcia-Olive I, Lacoma A, Ausina V, Dominguez J: Evaluation of interferon-gamma release assays in the diagnosis of recent tuberculosis infection in health care workers. PLoS One. 2009, 4: e6686-10.1371/journal.pone.0006686.CrossRefPubMedPubMedCentral
14.
Dominguez J, De Souza-Galvao M, Ruiz-Manzano J, Latorre I, Prat C, Lacoma A, Mila C, Jimenez MA, Blanco S, Maldonado J, et al: T-cell responses to the Mycobacterium tuberculosis-specific antigens in active tuberculosis patients at the beginning, during, and after antituberculosis treatment. Diagn Microbiol Infect Dis. 2009, 63: 43-51. 10.1016/j.diagmicrobio.2008.09.010.CrossRefPubMed
15.
Goletti D, Stefania C, Butera O, Amicosante M, Ernst M, Sauzullo I, Vullo V, Cirillo D, Borroni E, Markova R, et al: Accuracy of immunodiagnostic tests for active tuberculosis using single and combined results: a multicenter TBNET-Study. PLoS ONE. 2008, 3: e3417-10.1371/journal.pone.0003417.CrossRefPubMedPubMedCentral
16.
Pai M, Menzies D: Interferon-gamma release assays: what is their role in the diagnosis of active tuberculosis?. Clin Infect Dis. 2007, 44: 74-77. 10.1086/509927.CrossRefPubMed
17.
Lalvani A: Diagnosing tuberculosis infection in the 21st century: new tools to tackle an old enemy. Chest. 2007, 131: 1898-1906. 10.1378/chest.06-2471.CrossRefPubMed
18.
Latorre I, De Souza-Galvao M, Ruiz-Manzano J, Lacoma A, Prat C, Fuenzalida L, Altet N, Ausina V, Dominguez J: Quantitative evaluation of T-cell response after specific antigen stimulation in active and latent tuberculosis infection in adults and children. Diagn Microbiol Infect Dis. 2009, 65: 236-246. 10.1016/j.diagmicrobio.2009.07.015.CrossRefPubMed
19.
Rangaka MX, Wilkinson KA, Seldon R, Van Cutsem G, Meintjes GA, Morroni C, Mouton P, Diwakar L, Connell TG, Maartens G, Wilkinson RJ: Effect of HIV-1 infection on T-Cell-based and skin test detection of tuberculosis infection. Am J Respir Crit Care Med. 2007, 175: 514-520. 10.1164/rccm.200610-1439OC.CrossRefPubMed
20.
Chapman AL, Munkanta M, Wilkinson KA, Pathan AA, Ewer K, Ayles H, Reece WH, Mwinga A, Godfrey-Faussett P, Lalvani A: Rapid detection of active and latent tuberculosis infection in HIV-positive individuals by enumeration of Mycobacterium tuberculosis-specific T cells. AIDS. 2002, 16: 2285-2293. 10.1097/00002030-200211220-00008.CrossRefPubMed
21.
Dheda K, Lalvani A, Miller RF, Scott G, Booth H, Johnson MA, Zumla A, Rook GA: Performance of a T-cell-based diagnostic test for tuberculosis infection in HIV-infected individuals is independent of CD4 cell count. Aids. 2005, 19: 2038-2041. 10.1097/01.aids.0000191923.08938.5b.CrossRefPubMed
22.
Dominguez J, Latorre I, Altet N, Mateo L, De Souza-Galvão M, Ruiz-Manzano J, Ausina V: IFN-gamma release assays to diagnose tuberculosis infection in the immunocompromised individual. Expert Rev Resp Med. 2009, 3: 309-327. 10.1586/ers.09.20.CrossRef
23.
Mandalakas AM, Hesseling AC, Chegou NN, Kirchner HL, Zhu X, Marais BJ, Black GF, Beyers N, Walzl G: High level of discordant IGRA results in HIV-infected adults and children. Int J Tuberc Lung Dis. 2008, 12: 417-423.PubMed
24.
Richeldi L, Losi M, D'Amico R, Luppi M, Ferrari A, Mussini C, Codeluppi M, Cocchi S, Prati F, Paci V, et al: Performance of tests for latent tuberculosis in different groups of immunocompromised patients. Chest. 2009, 136: 198-204. 10.1378/chest.08-2575.CrossRefPubMed
25.
Talati NJ, Seybold U, Humphrey B, Aina A, Tapia J, Weinfurter P, Albalak R, Blumberg HM: Poor concordance between interferon-gamma release assays and tuberculin skin tests in diagnosis of latent tuberculosis infection among HIV-infected individuals. BMC Infect Dis. 2009, 9: 15-10.1186/1471-2334-9-15.CrossRefPubMedPubMedCentral
26.
Leidl L, Mayanja-Kizza H, Sotgiu G, Baseke J, Ernst M, Hirsch C, Goletti D, Toossi Z, Lange C: Relationship of immunodiagnostic assays for tuberculosis and numbers of circulating CD4+ T-cells in HIV-infection. Eur Respir J. 2009, 35: 419-426.
27.
Rivas I, Latorre I, Sanvisens A, Dominguez J, Tor J, Prat C, Rey-Joly C, Muga R: Prospective evaluation of latent tuberculosis with interferon-gamma release assays in drug and alcohol abusers. Epidemiol Infect. 2009, 137: 1342-1347. 10.1017/S0950268809002131.CrossRefPubMed
28.
Generalitat de Catalunya. Departament de Salut: Programa de prevenció i control de la tuberculosi a Catalunya. Situació epidemiològica i tendència de l'endèmia tuberculosa a Catalunya. Informe anual. 2008
29.
Ruiz-Manzano J, Blanquer R, Calpe JL, Caminero JA, Cayla J, Dominguez JA, Garcia JM, Vidal R: [Diagnosis and treatment of tuberculosis]. Arch Bronconeumol. 2008, 44: 551-566. 10.1157/13126836.CrossRefPubMed
30.
Brock I, Ruhwald M, Lundgren B, Westh H, Mathiesen LR, Ravn P: Latent tuberculosis in HIV positive, diagnosed by the M. tuberculosis specific interferon-gamma test. Respir Res. 2006, 7: 56-10.1186/1465-9921-7-56.CrossRefPubMedPubMedCentral
31.
Luetkemeyer AF, Charlebois ED, Flores LL, Bangsberg DR, Deeks SG, Martin JN, Havlir DV: Comparison of an interferon-gamma release assay with tuberculin skin testing in HIV-infected individuals. Am J Respir Crit Care Med. 2007, 175: 737-742. 10.1164/rccm.200608-1088OC.CrossRefPubMedPubMedCentral
32.
Stephan C, Wolf T, Goetsch U, Bellinger O, Nisius G, Oremek G, Rakus Z, Gottschalk R, Stark S, Brodt HR, Staszewski S: Comparing QuantiFERON-tuberculosis gold, T-SPOT tuberculosis and tuberculin skin test in HIV-infected individuals from a low prevalence tuberculosis country. Aids. 2008, 22: 2471-2479. 10.1097/QAD.0b013e3283188415.CrossRefPubMed
33.
Jones S, de Gijsel D, Wallach FR, Gurtman AC, Shi Q, Sacks H: Utility of QuantiFERON-TB Gold in-tube testing for latent TB infection in HIV-infected individuals. Int J Tuberc Lung Dis. 2007, 11: 1190-1195.PubMed
34.
Jiang W, Shao L, Zhang Y, Zhang S, Meng C, Xu Y, Huang L, Wang Y, Wang Y, Weng X, Zhang W: High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-gamma release assay among HIV-infected individuals in BCG-vaccinated area. BMC Immunol. 2009, 10: 31-10.1186/1471-2172-10-31.CrossRefPubMedPubMedCentral
35.
Altet-Gómez M, De Souza-Galvao M, Latorre I, Milá C, Jiménez M, Solsona J, Cantos A, Zamora J, Ruiz Manzano J, Ausina V, Domínguez J: Diagnosing TB infection in children: analysis of discordances using in vitrotests and tuberculin skin test. Eur Respir J. 2010,
36.
Aabye MG, Ravn P, PrayGod G, Jeremiah K, Mugomela A, Jepsen M, Faurholt D, Range N, Friis H, Changalucha J, Andersen AB: The impact of HIV infection and CD4 cell count on the performance of an interferon gamma release assay in patients with pulmonary tuberculosis. PLoS One. 2009, 4: e4220-10.1371/journal.pone.0004220.CrossRefPubMedPubMedCentral
37.
Raby E, Moyo M, Devendra A, Banda J, De Haas P, Ayles H, Godfrey-Faussett P: The effects of HIV on the sensitivity of a whole blood IFN-gamma release assay in Zambian adults with active tuberculosis. PLoS One. 2008, 3: e2489-10.1371/journal.pone.0002489.CrossRefPubMedPubMedCentral
38.
Cattamanchi A, Ssewenyana I, Davis JL, Huang L, Worodria W, den Boon S, Yoo S, Andama A, Hopewell PC, Cao H: Role of interferon-gamma release assays in the diagnosis of pulmonary tuberculosis in patients with advanced HIV infection. BMC Infect Dis. 2010, 10: 75-10.1186/1471-2334-10-75.CrossRefPubMedPubMedCentral
39.
Converse PJ, Jones SL, Astemborski J, Vlahov D, Graham NM: Comparison of a tuberculin interferon-gamma assay with the tuberculin skin test in high-risk adults: effect of human immunodeficiency virus infection. J Infect Dis. 1997, 176: 144-150. 10.1086/514016.CrossRefPubMed
40.
Clark SA, Martin SL, Pozniak A, Steel A, Ward B, Dunning J, Henderson DC, Nelson M, Gazzard B, Kelleher P: Tuberculosis antigen-specific immune responses can be detected using enzyme-linked immunospot technology in human immunodeficiency virus (HIV)-1 patients with advanced disease. Clin Exp Immunol. 2007, 150: 238-244. 10.1111/j.1365-2249.2007.03477.x.CrossRefPubMedPubMedCentral
41.
Oni T, Patel J, Gideon HP, Seldon R, Wood K, Hlombe Y, Wilkinson KA, Rangaka MX, Mendelson M, Wilkinson RJ: Enhanced diagnosis of HIV-1 associated tuberculosis by relating T-SPOT.TB and CD4 counts. Eur Respir J. 2010, 36: 594-600. 10.1183/09031936.00171509.CrossRefPubMedPubMedCentral
42.
Latorre I, De Souza-Galvão M, Ruiz-Manzano J, Lacoma A, Prat C, Altet N, Ausina V, J D: Evaluating the non-tuberculous mycobacteria effect in the tuberculosis infection diagnosis. Eur Respir J. 2010, 35: 338-342. 10.1183/09031936.00196608.CrossRefPubMed
Metadata
Title
IFN-γ response on T-cell based assays in HIV-infected patients for detection of tuberculosis infection
Authors
Irene Latorre
Xavier Martínez-Lacasa
Roser Font
Alicia Lacoma
Jordi Puig
Cristina Tural
Josep Lite
Cristina Prat
Eva Cuchi
Vicente Ausina
Jose Domínguez
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2010
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-10-348

Other articles of this Issue 1/2010

BMC Infectious Diseases 1/2010 Go to the issue

Research article

High rate of pneumococcal bacteremia in a prospective cohort of older children and adults in an area of high HIV prevalence in rural western Kenya

Research article

Community acquired bacterial meningitis in Cuba: a follow up of a decade

Research article

The burden and characteristics of tuberculosis/human immunodeficiency virus (TB/HIV) in South Korea: a study from a population database and a survey

Commentary

Searching for the elusive typhoid diagnostic

Research article

Survey of HBsAg-positive pregnant women and their infants regarding measures to prevent maternal-infantile transmission

Debate

The epidemiology of bacterial vaginosis in relation to sexual behaviour
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits