Repeatedly negative tuberculin skin tests followed by active tuberculosis in an immunocompetent individual

Abstract Background The online Tuberculin Skin Test/Interferon Gamma Release Assay (TST/IGRA) Interpreter V3.0 (TSTin3D), a tool for estimating the risk of active tuberculosis (TB) in individuals with latent TB infection (LTBI), has been in use for more than a decade, but its predictive performance has never been evaluated. Methods People with a positive TST or IGRA result from 1985 to 2015 were identified using a health data linkage that involved migrants to British Columbia, Canada. Comorbid conditions at the time of LTBI testing were identified from physician claims, hospitalizations, vital statistics, outpatient prescriptions, and kidney and HIV databases. The risk of developing active TB within 2 and 5 years was estimated using TSTin3D. The discrimination and calibration of these estimates were evaluated. Results A total of 37 163 individuals met study inclusion criteria; 10.4% were tested by IGRA. Generally, the TSTin3D algorithm assigned higher risks to demographic and clinical groups known to have higher active TB risks. Concordance estimates ranged from 0.66 to 0.68 in 2- and 5-year time frames. Comparing predicted to observed counts suggests that TSTin3D overestimates active TB risks and that overestimation increases over time (with relative bias of 3% and 12% in 2- and 5-year periods, respectively). Calibration plots also suggest that overestimation increases toward the upper end of the risk spectrum. Conclusions TSTin3D can discriminate adequately between people who developed and did not develop active TB in this linked database of migrants with predominately positive skin tests. Further work is needed to improve TSTin3D’s calibration.

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Analysis of the chemoprophylactic effect on close contacts of patients with active tuberculosis and positive tuberculin skin tests

Family Medicine and Community Health ◽

10.15212/fmch.2014.0126 ◽

2014 ◽

Vol 2 (3) ◽

pp. 12-17

Author(s):

Cunzhi Lin ◽

Fangfang Wang ◽

Jinfeng Li ◽

Jianxin Du ◽

Hairong Wang ◽

...

Keyword(s):

Active Tuberculosis ◽

Skin Tests ◽

Close Contacts

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Prevalence of latent Mycobacterium tuberculosis infection in prisoners

Jornal Brasileiro de Pneumologia ◽

10.1590/s1806-37562016000000001 ◽

2016 ◽

Vol 42 (5) ◽

pp. 348-355 ◽

Cited By ~ 8

Author(s):

Pedro Daibert de Navarro ◽

Isabela Neves de Almeida ◽

Afrânio Lineu Kritski ◽

Maria das Graças Ceccato ◽

Mônica Maria Delgado Maciel ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Minas Gerais ◽

Active Tuberculosis ◽

Tuberculosis Infection ◽

Skin Tests ◽

Mycobacterium Tuberculosis Infection ◽

Inhaled Drugs ◽

Cross Sectional ◽

Tuberculosis Patients ◽

Study Results

ABSTRACT Objective: To determine the prevalence of and the factors associated with latent Mycobacterium tuberculosis infection (LTBI) in prisoners in the state of Minas Gerais, Brazil. Methods: This was a cross-sectional cohort study conducted in two prisons in Minas Gerais. Tuberculin skin tests were performed in the individuals who agreed to participate in the study. Results: A total of 1,120 individuals were selected for inclusion in this study. The prevalence of LTBI was 25.2%. In the multivariate analysis, LTBI was associated with self-reported contact with active tuberculosis patients within prisons (adjusted OR = 1.51; 95% CI: 1.05-2.18) and use of inhaled drugs (adjusted OR = 1.48; 95% CI: 1.03-2.13). Respiratory symptoms were identified in 131 (11.7%) of the participants. Serological testing for HIV was performed in 940 (83.9%) of the participants, and the result was positive in 5 (0.5%). Two cases of active tuberculosis were identified during the study period. Conclusions: Within the prisons under study, the prevalence of LTBI was high. In addition, LTBI was associated with self-reported contact with active tuberculosis patients and with the use of inhaled drugs. Our findings demonstrate that it is necessary to improve the conditions in prisons, as well as to introduce strategies, such as chest X-ray screening, in order to detect tuberculosis cases and, consequently, reduce M. tuberculosis infection within the prison system.

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Tuberculin-Purified Protein Derivative-, MPT-64-, and ESAT-6-Stimulated Gamma Interferon Responses in Medical Students before and after Mycobacterium bovis BCG Vaccination and in Patients with Tuberculosis

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.6.6.934-937.1999 ◽

1999 ◽

Vol 6 (6) ◽

pp. 934-937 ◽

Cited By ~ 66

Author(s):

P. D. R. Johnson ◽

R. L. Stuart ◽

M. L. Grayson ◽

D. Olden ◽

A. Clancy ◽

...

Keyword(s):

Medical Students ◽

Venous Blood ◽

Gamma Interferon ◽

Active Tuberculosis ◽

Skin Tests ◽

Purified Protein Derivative ◽

Before And After ◽

Specific Proteins ◽

Ifn Γ ◽

Interferon Responses

ABSTRACT QuantiFERON-TB (QIFN) (CSL Limited) is a whole-blood assay for the recognition of infection withMycobacterium tuberculosis. QIFN measures gamma interferon (IFN-γ) production when purified protein derivatives (PPDs) of mycobacteria are incubated with venous blood samples. The specificity of QIFN in medical students before and after BCG immunization was assessed, and sensitivity in patients with tuberculosis was assessed. Antigens were PPD derived from M. tuberculosis and twoM. tuberculosis-specific proteins, ESAT-6 and MPT-64. Of 60 medical students, all of whom had 0-mm tuberculin skin tests (TSTs) at study entry, 58 (97%) were initially classified as negative forM. tuberculosis infection by PPD QIFN. Five months after BCG immunization, 7 of 54 students (13%) had a TST result of ≥10 mm and 11 of 54 students (20%) tested positive by PPD QIFN. ESAT-6- and MPT-64-stimulated IFN-γ responses in the medical students were negative prior to and after BCG immunization. For patients with active tuberculosis, 12 of 19 (63%) were positive by PPD QIFN, 11 of 19 (58%) were positive by ESAT-6 QIFN, and 0 of 12 were positive by MPT-64 QIFN. In conclusion, PPD QIFN was negative in 97% of a low-risk population who had not received BCG and who had negative TSTs. The specificities of both the TST and PPD QIFN were reduced following BCG immunization. PPD QIFN and ESAT-6 QIFN were of similar and moderate sensitivity in patients with active tuberculosis, but ESAT-6 QIFN is likely to be more specific because it is not influenced by past BCG exposure.

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Diagnosis of Active Tuberculosis in China Using an In-House Gamma Interferon Enzyme-Linked Immunospot Assay

Clinical and Vaccine Immunology ◽

10.1128/cvi.00044-09 ◽

2009 ◽

Vol 16 (6) ◽

pp. 879-884 ◽

Cited By ~ 39

Author(s):

Xinchun Chen ◽

Qianting Yang ◽

Mingxia Zhang ◽

Michael Graner ◽

Xiuyun Zhu ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Elispot Assay ◽

Lung Diseases ◽

Gamma Interferon ◽

Active Tuberculosis ◽

Skin Tests ◽

Healthy Controls ◽

Specificity And Sensitivity ◽

Different Populations ◽

Ifn Γ

ABSTRACT Gamma interferon (IFN-γ) release assays have been proven to be useful in the diagnosis of Mycobacterium tuberculosis infection. Nevertheless, their specificity and sensitivity vary among the different populations studied. Here, we evaluate the value of an in-house IFN-γ enzyme-linked immunospot (ELISPOT) assay in the diagnosis of active tuberculosis (TB) in Shenzhen, China, where the prevalence of tuberculosis is severe and Mycobacterium bovis BCG vaccination is mandatory at birth. A total of 305 patients with active tuberculosis, 18 patients with nontuberculosis lung diseases, and 202 healthy controls were recruited in this study. Among them, 156 individuals were simultaneously tested for IFN-γ responses by the commercial QuantiFERON-TB Gold in-tube (QFT-IT) assay. Tuberculin skin tests (TST) were performed with 202 healthy controls. The overall sensitivities of the ELISPOT and QFT-IT assays for active tuberculosis were 83.60% and 80.85%, respectively; the specificities were 76.6% and 73.26%, respectively. The IFN-γ ELISPOT responses, but not those of the TST, were significantly correlated with TB exposure (r = −0.6040, P < 0.0001). The sensitivities of the ELISPOT assay varied for patients with different forms of tuberculosis, with the highest sensitivity for patients with sputum-positive pulmonary tuberculosis (89.89%) and the lowest for those with tuberculous meningitis (62.5%). In conclusion, the IFN-γ ELISPOT assay is a useful adjunct to current tests for diagnosis of active TB in China. The ELISPOT assay is more accurate than TST in identifying TB infections.

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METHODS OF SPECIFIC DIAGNOSIS OF TUBERCULOSIS: A MODERN VIEW ON THE PROBLEM

Science and Innovations in Medicine ◽

10.35693/2500-1388-2017-0-2-44-51 ◽

2017 ◽

Vol 2 (2) ◽

pp. 44-51 ◽

Cited By ~ 1

Author(s):

OS S Prylutskyi ◽

YuD D Rogovaya

Keyword(s):

Latent Tuberculosis ◽

Active Tuberculosis ◽

Diagnostic Methods ◽

Screening Tests ◽

Skin Tests ◽

Immunological Methods ◽

Tuberculous Infection ◽

Diagnostic Significance ◽

Advantages And Disadvantages ◽

Cell Mediated Immune Response

This review presents modern views on the problems of immunodiagnosis of tuberculosis. We have examined the advisability of the use of immunological methods for diagnosis of active tuberculosis and detection of latent tuberculous infection. It is shown that nowadays the use of serological diagnostic methods is not recommended because of contradictory information about their accuracy and limited diagnostic significance. Advantages and disadvantages of current methods of assessment of cell-mediated immune response that are used as screening tests for diagnosis of latent tuberculosis have been analyzed. We point to advisability of combination of different methods that are available nowadays with the use of skin tests as the first step of diagnosis, and improvement of techniques of antigens injections that are used for them.

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