Discordance of tuberculin skin test and interferon gamma release assay in recently exposed household contacts of pulmonary TB cases in Brazil

Rodrigo Ribeiro-Rodrigues, Soyeon Kim, Flávia Dias Coelho Da Silva, Aleksandra Uzelac, Lauren Collins, Moíses Palaci, David Alland, Reynaldo Dietze, Jerrold J. Ellner, Edward Jones-López, Padmini Salgame

Research output: Contribution to journalArticle

Abstract

Interferon-gamma (IFN-γ) release assays (IGRAs) such as the Quantiferon Gold In-tube test are in vitro assays that measure IFN-γ release from T cells in response to M. tuberculosis (Mtb)-specific antigens. Unlike the tuberculin skin test (TST), IGRA is specific and able to distinguish Mtb-infection from BCG vaccination. In this study we evaluated the concordance between TST and IGRA and the efficacy of IGRA in diagnosing new Mtb infection in household contacts (HHC) of pulmonary tuberculosis (PTB) cases. A total of 357 HHC of TB cases in Vitória, Brazil were studied. A TST was performed within 2 weeks following enrollment of the HHC and if negative a second TST was performed at 8-12 weeks. HHC were categorized as initially TST positive (TST+), persistently TST negative (TST-), or TST converters (TSTc), the latter representative of new infection. IGRA was performed at 8-12 weeks following enrollment and the test results were positive in 82% of TST+, 48% of TSTc, and 12% of TST-, indicating poor concordance between the two test results among HHC in each category. Evaluating CXCL10 levels in a subset of IGRA supernatants or lowering the IGRA cutoff value to define a positive test increased agreement between TST and IGRA test results. However, ROC curves demonstrated that this resulted in a trade-off between sensitivity and specificity of IGRA with respect to TST. Together, the findings suggest that until the basis for the discordance between TST and IGRA is fully understood, it may be necessary to utilize both tests to diagnose new Mtb infection in recently exposed HHC. Operationally, in IGRA negative HHC, it may be useful to employ a lower cutoff value for IGRA to allow closer monitoring for potential conversion.

Original languageEnglish (US)
Article numbere96564
JournalPLoS One
Volume9
Issue number5
DOIs
StatePublished - May 12 2014
Externally publishedYes

Fingerprint

Interferon-gamma Release Tests
Tuberculin Test
tuberculin
skin tests
Tuberculin
Skin Tests
interferon-gamma
Interferon-gamma
Brazil
households
Assays
Skin
lungs
Lung
assays
tuberculosis
Tuberculosis
testing
Infection
infection

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ribeiro-Rodrigues, R., Kim, S., Coelho Da Silva, F. D., Uzelac, A., Collins, L., Palaci, M., ... Salgame, P. (2014). Discordance of tuberculin skin test and interferon gamma release assay in recently exposed household contacts of pulmonary TB cases in Brazil. PLoS One, 9(5), [e96564]. https://doi.org/10.1371/journal.pone.0096564

Discordance of tuberculin skin test and interferon gamma release assay in recently exposed household contacts of pulmonary TB cases in Brazil. / Ribeiro-Rodrigues, Rodrigo; Kim, Soyeon; Coelho Da Silva, Flávia Dias; Uzelac, Aleksandra; Collins, Lauren; Palaci, Moíses; Alland, David; Dietze, Reynaldo; Ellner, Jerrold J.; Jones-López, Edward; Salgame, Padmini.

In: PLoS One, Vol. 9, No. 5, e96564, 12.05.2014.

Research output: Contribution to journalArticle

Ribeiro-Rodrigues, R, Kim, S, Coelho Da Silva, FD, Uzelac, A, Collins, L, Palaci, M, Alland, D, Dietze, R, Ellner, JJ, Jones-López, E & Salgame, P 2014, 'Discordance of tuberculin skin test and interferon gamma release assay in recently exposed household contacts of pulmonary TB cases in Brazil', PLoS One, vol. 9, no. 5, e96564. https://doi.org/10.1371/journal.pone.0096564
Ribeiro-Rodrigues, Rodrigo ; Kim, Soyeon ; Coelho Da Silva, Flávia Dias ; Uzelac, Aleksandra ; Collins, Lauren ; Palaci, Moíses ; Alland, David ; Dietze, Reynaldo ; Ellner, Jerrold J. ; Jones-López, Edward ; Salgame, Padmini. / Discordance of tuberculin skin test and interferon gamma release assay in recently exposed household contacts of pulmonary TB cases in Brazil. In: PLoS One. 2014 ; Vol. 9, No. 5.
@article{6373ace9ce204ca7a2e81cff05609871,
title = "Discordance of tuberculin skin test and interferon gamma release assay in recently exposed household contacts of pulmonary TB cases in Brazil",
abstract = "Interferon-gamma (IFN-γ) release assays (IGRAs) such as the Quantiferon Gold In-tube test are in vitro assays that measure IFN-γ release from T cells in response to M. tuberculosis (Mtb)-specific antigens. Unlike the tuberculin skin test (TST), IGRA is specific and able to distinguish Mtb-infection from BCG vaccination. In this study we evaluated the concordance between TST and IGRA and the efficacy of IGRA in diagnosing new Mtb infection in household contacts (HHC) of pulmonary tuberculosis (PTB) cases. A total of 357 HHC of TB cases in Vit{\'o}ria, Brazil were studied. A TST was performed within 2 weeks following enrollment of the HHC and if negative a second TST was performed at 8-12 weeks. HHC were categorized as initially TST positive (TST+), persistently TST negative (TST-), or TST converters (TSTc), the latter representative of new infection. IGRA was performed at 8-12 weeks following enrollment and the test results were positive in 82{\%} of TST+, 48{\%} of TSTc, and 12{\%} of TST-, indicating poor concordance between the two test results among HHC in each category. Evaluating CXCL10 levels in a subset of IGRA supernatants or lowering the IGRA cutoff value to define a positive test increased agreement between TST and IGRA test results. However, ROC curves demonstrated that this resulted in a trade-off between sensitivity and specificity of IGRA with respect to TST. Together, the findings suggest that until the basis for the discordance between TST and IGRA is fully understood, it may be necessary to utilize both tests to diagnose new Mtb infection in recently exposed HHC. Operationally, in IGRA negative HHC, it may be useful to employ a lower cutoff value for IGRA to allow closer monitoring for potential conversion.",
author = "Rodrigo Ribeiro-Rodrigues and Soyeon Kim and {Coelho Da Silva}, {Fl{\'a}via Dias} and Aleksandra Uzelac and Lauren Collins and Mo{\'i}ses Palaci and David Alland and Reynaldo Dietze and Ellner, {Jerrold J.} and Edward Jones-L{\'o}pez and Padmini Salgame",
year = "2014",
month = "5",
day = "12",
doi = "10.1371/journal.pone.0096564",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

TY - JOUR

T1 - Discordance of tuberculin skin test and interferon gamma release assay in recently exposed household contacts of pulmonary TB cases in Brazil

AU - Ribeiro-Rodrigues, Rodrigo

AU - Kim, Soyeon

AU - Coelho Da Silva, Flávia Dias

AU - Uzelac, Aleksandra

AU - Collins, Lauren

AU - Palaci, Moíses

AU - Alland, David

AU - Dietze, Reynaldo

AU - Ellner, Jerrold J.

AU - Jones-López, Edward

AU - Salgame, Padmini

PY - 2014/5/12

Y1 - 2014/5/12

N2 - Interferon-gamma (IFN-γ) release assays (IGRAs) such as the Quantiferon Gold In-tube test are in vitro assays that measure IFN-γ release from T cells in response to M. tuberculosis (Mtb)-specific antigens. Unlike the tuberculin skin test (TST), IGRA is specific and able to distinguish Mtb-infection from BCG vaccination. In this study we evaluated the concordance between TST and IGRA and the efficacy of IGRA in diagnosing new Mtb infection in household contacts (HHC) of pulmonary tuberculosis (PTB) cases. A total of 357 HHC of TB cases in Vitória, Brazil were studied. A TST was performed within 2 weeks following enrollment of the HHC and if negative a second TST was performed at 8-12 weeks. HHC were categorized as initially TST positive (TST+), persistently TST negative (TST-), or TST converters (TSTc), the latter representative of new infection. IGRA was performed at 8-12 weeks following enrollment and the test results were positive in 82% of TST+, 48% of TSTc, and 12% of TST-, indicating poor concordance between the two test results among HHC in each category. Evaluating CXCL10 levels in a subset of IGRA supernatants or lowering the IGRA cutoff value to define a positive test increased agreement between TST and IGRA test results. However, ROC curves demonstrated that this resulted in a trade-off between sensitivity and specificity of IGRA with respect to TST. Together, the findings suggest that until the basis for the discordance between TST and IGRA is fully understood, it may be necessary to utilize both tests to diagnose new Mtb infection in recently exposed HHC. Operationally, in IGRA negative HHC, it may be useful to employ a lower cutoff value for IGRA to allow closer monitoring for potential conversion.

AB - Interferon-gamma (IFN-γ) release assays (IGRAs) such as the Quantiferon Gold In-tube test are in vitro assays that measure IFN-γ release from T cells in response to M. tuberculosis (Mtb)-specific antigens. Unlike the tuberculin skin test (TST), IGRA is specific and able to distinguish Mtb-infection from BCG vaccination. In this study we evaluated the concordance between TST and IGRA and the efficacy of IGRA in diagnosing new Mtb infection in household contacts (HHC) of pulmonary tuberculosis (PTB) cases. A total of 357 HHC of TB cases in Vitória, Brazil were studied. A TST was performed within 2 weeks following enrollment of the HHC and if negative a second TST was performed at 8-12 weeks. HHC were categorized as initially TST positive (TST+), persistently TST negative (TST-), or TST converters (TSTc), the latter representative of new infection. IGRA was performed at 8-12 weeks following enrollment and the test results were positive in 82% of TST+, 48% of TSTc, and 12% of TST-, indicating poor concordance between the two test results among HHC in each category. Evaluating CXCL10 levels in a subset of IGRA supernatants or lowering the IGRA cutoff value to define a positive test increased agreement between TST and IGRA test results. However, ROC curves demonstrated that this resulted in a trade-off between sensitivity and specificity of IGRA with respect to TST. Together, the findings suggest that until the basis for the discordance between TST and IGRA is fully understood, it may be necessary to utilize both tests to diagnose new Mtb infection in recently exposed HHC. Operationally, in IGRA negative HHC, it may be useful to employ a lower cutoff value for IGRA to allow closer monitoring for potential conversion.

UR - http://www.scopus.com/inward/record.url?scp=84901259401&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901259401&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0096564

DO - 10.1371/journal.pone.0096564

M3 - Article

C2 - 24819060

AN - SCOPUS:84901259401

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

M1 - e96564

ER -