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 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.
authors.affiliation: Cellular and Molecular Immunology Laboratory, Núcleo de Doenças Infecciosas, UFES, Vitória, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ribeiro-Rodrigues
authors.affiliation: Department of Preventive Medicine and Community Health, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, United States of America.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Cellular and Molecular Immunology Laboratory, Núcleo de Doenças Infecciosas, UFES, Vitória, Brazil.
authors.forename: Flávia Dias
authors.initials: FD
authors.lastname: Coelho da Silva
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, United States of America.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Uzelac
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Lauren
authors.initials: L
authors.lastname: Collins
authors.affiliation: Mycobacteriology Laboratory, Núcleo de Doenças Infecciosas (NDI), Universidade Federal do Espírito Santo (UFES), Vitória, Brazil.
authors.forename: Moíses
authors.initials: M
authors.lastname: Palaci
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Alland
authors.affiliation: Cellular and Molecular Immunology Laboratory, Núcleo de Doenças Infecciosas, UFES, Vitória, Brazil.
authors.forename: Reynaldo
authors.initials: R
authors.lastname: Dietze
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Jerrold J
authors.initials: JJ
authors.lastname: Ellner
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Edward
authors.initials: E
authors.lastname: Jones-López
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey, United States of America.
authors.forename: Padmini
authors.initials: P
authors.lastname: Salgame
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D005260:Female; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000379:methods* / Q000592:standards*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D014374:Tuberculin Test / Q000379:methods* / Q000592:standards*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis*; D055815:Young Adult