Risk assessment of tuberculosis in immunocompromised patients:  A TBNET study

Martina Sester; Frank van Leth; Judith Bruchfeld; Dragos Bumbacea; Daniela M Cirillo; Asli Gorek Dilektasli; José Domínguez; Raquel Duarte; Martin Ernst; Fusun Oner Eyuboglu; Irini Gerogianni; Enrico Girardi; Delia Goletti; Jean-Paul Janssens; Inger Julander; Berit Lange; Irene Latorre; Monica Losi; Roumiana Markova; Alberto Matteelli; Heather Milburn; Pernille Ravn; Theresia Scholman; Paola M Soccal; Marina Straub; Dirk Wagner; Timo Wolf; Aslihan Yalcin; Christoph Lange; TBNET

doi:10.1164/rccm.201405-0967oc

Risk assessment of tuberculosis in immunocompromised patients: A TBNET study

Martina Sester, Frank van Leth, Judith Bruchfeld, Dragos Bumbacea, Daniela M Cirillo, Asli Gorek Dilektasli, José Domínguez, Raquel Duarte, Martin Ernst, Fusun Oner Eyuboglu, Irini Gerogianni, Enrico Girardi, Delia Goletti, Jean-Paul Janssens, Inger Julander, Berit Lange, Irene Latorre, Monica Losi, Roumiana Markova, Alberto MatteelliHeather Milburn, Pernille Ravn, Theresia Scholman, Paola M Soccal, Marina Straub, Dirk Wagner, Timo Wolf, Aslihan Yalcin, Christoph Lange, TBNET

Department of Drug Design and Pharmacology

139 Citations (Scopus)

Abstract

RATIONALE: In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency.

OBJECTIVES: This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis.

METHODS: Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up.

MEASUREMENTS AND MAIN RESULTS: Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy.

CONCLUSIONS: Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).

Original language	English
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	190
Issue number	10
Pages (from-to)	1168-76
Number of pages	9
ISSN	1073-449X
DOIs	https://doi.org/10.1164/rccm.201405-0967oc
Publication status	Published - 15 Nov 2014

Keywords

Adult
Aged
Arthritis, Rheumatoid
Cohort Studies
Cross-Sectional Studies
Female
HIV Infections
Humans
Immunocompromised Host
Interferon-gamma Release Tests
Kidney Failure, Chronic
Latent Tuberculosis
Male
Middle Aged
Organ Transplantation
Risk Assessment
Stem Cell Transplantation
Tuberculin Test

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1164/rccm.201405-0967oc

Cite this

Sester, M., van Leth, F., Bruchfeld, J., Bumbacea, D., Cirillo, D. M., Dilektasli, A. G., Domínguez, J., Duarte, R., Ernst, M., Eyuboglu, F. O., Gerogianni, I., Girardi, E., Goletti, D., Janssens, J-P., Julander, I., Lange, B., Latorre, I., Losi, M., Markova, R., ... TBNET (2014). Risk assessment of tuberculosis in immunocompromised patients: A TBNET study. American Journal of Respiratory and Critical Care Medicine, 190(10), 1168-76. https://doi.org/10.1164/rccm.201405-0967oc

Sester, M, van Leth, F, Bruchfeld, J, Bumbacea, D, Cirillo, DM, Dilektasli, AG, Domínguez, J, Duarte, R, Ernst, M, Eyuboglu, FO, Gerogianni, I, Girardi, E, Goletti, D, Janssens, J-P, Julander, I, Lange, B, Latorre, I, Losi, M, Markova, R, Matteelli, A, Milburn, H, Ravn, P, Scholman, T, Soccal, PM, Straub, M, Wagner, D, Wolf, T, Yalcin, A, Lange, C & TBNET 2014, 'Risk assessment of tuberculosis in immunocompromised patients: A TBNET study', American Journal of Respiratory and Critical Care Medicine, vol. 190, no. 10, pp. 1168-76. https://doi.org/10.1164/rccm.201405-0967oc

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title = "Risk assessment of tuberculosis in immunocompromised patients: A TBNET study",

abstract = "RATIONALE: In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency.OBJECTIVES: This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis.METHODS: Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up.MEASUREMENTS AND MAIN RESULTS: Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy.CONCLUSIONS: Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).",

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author = "Martina Sester and {van Leth}, Frank and Judith Bruchfeld and Dragos Bumbacea and Cirillo, {Daniela M} and Dilektasli, {Asli Gorek} and Jos{\'e} Dom{\'i}nguez and Raquel Duarte and Martin Ernst and Eyuboglu, {Fusun Oner} and Irini Gerogianni and Enrico Girardi and Delia Goletti and Jean-Paul Janssens and Inger Julander and Berit Lange and Irene Latorre and Monica Losi and Roumiana Markova and Alberto Matteelli and Heather Milburn and Pernille Ravn and Theresia Scholman and Soccal, {Paola M} and Marina Straub and Dirk Wagner and Timo Wolf and Aslihan Yalcin and Christoph Lange and TBNET",

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doi = "10.1164/rccm.201405-0967oc",

language = "English",

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journal = "American Journal of Respiratory and Critical Care Medicine",

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TY - JOUR

T1 - Risk assessment of tuberculosis in immunocompromised patients

T2 - A TBNET study

AU - Sester, Martina

AU - van Leth, Frank

AU - Bruchfeld, Judith

AU - Bumbacea, Dragos

AU - Cirillo, Daniela M

AU - Dilektasli, Asli Gorek

AU - Domínguez, José

AU - Duarte, Raquel

AU - Ernst, Martin

AU - Eyuboglu, Fusun Oner

AU - Gerogianni, Irini

AU - Girardi, Enrico

AU - Goletti, Delia

AU - Janssens, Jean-Paul

AU - Julander, Inger

AU - Lange, Berit

AU - Latorre, Irene

AU - Losi, Monica

AU - Markova, Roumiana

AU - Matteelli, Alberto

AU - Milburn, Heather

AU - Ravn, Pernille

AU - Scholman, Theresia

AU - Soccal, Paola M

AU - Straub, Marina

AU - Wagner, Dirk

AU - Wolf, Timo

AU - Yalcin, Aslihan

AU - Lange, Christoph

AU - TBNET

PY - 2014/11/15

Y1 - 2014/11/15

N2 - RATIONALE: In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency.OBJECTIVES: This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis.METHODS: Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up.MEASUREMENTS AND MAIN RESULTS: Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy.CONCLUSIONS: Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).

AB - RATIONALE: In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency.OBJECTIVES: This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis.METHODS: Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up.MEASUREMENTS AND MAIN RESULTS: Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy.CONCLUSIONS: Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).

KW - Adult

KW - Aged

KW - Arthritis, Rheumatoid

KW - Cohort Studies

KW - Cross-Sectional Studies

KW - Female

KW - HIV Infections

KW - Humans

KW - Immunocompromised Host

KW - Interferon-gamma Release Tests

KW - Kidney Failure, Chronic

KW - Latent Tuberculosis

KW - Male

KW - Middle Aged

KW - Organ Transplantation

KW - Risk Assessment

KW - Stem Cell Transplantation

KW - Tuberculin Test

U2 - 10.1164/rccm.201405-0967oc

DO - 10.1164/rccm.201405-0967oc

M3 - Journal article

C2 - 25303140

SN - 1073-449X

VL - 190

SP - 1168

EP - 1176

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 10

ER -