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Setting: The infection with Mycobacterium tuberculosis gives a delayed immune response, measured by the tuberculine skin test. We present a new technique for evaluation based on automatic detection and measurement of skin temperature due to infrared emission., Design: 34 subjects (46.8±16.9 years) (12/22, M/F) with suspected tuberculosis disease were examined with an IR thermal camera, 48 h after tuberculin skin injection., Results: In 20 subjects, IR analysis was positive for tuberculine test. Mean temperature of injection area was higher, around 1°C, for the positive group (36.2±1.1°C positive group; 35.1±1.6°C negative group, p<0.02 T test for unpaired groups)., Conclusion: IR image analysis achieves similar estimation of tuberculin reaction as the visual evaluation, based on higher temperature due to increased heat radiation from the skin lesion., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Rationale: The identification of patients with latent tuberculosis infection, who are at higher risk to develop active disease, is an important component of disease control., Objectives: We aim to compare the usefulness of the QuantiFERON-TB Gold in-tube assay and the tuberculin skin test to predict the development of active tuberculosis during follow-up, using positive and negative predictive values, positive likelihood ratios, and stratified level of risk., Methods: The study included contacts of tuberculosis cases diagnosed between 2007 and 2009. All contacts included were from the first circle of exposure. Tuberculin skin test and QuantiFERON test were performed and a chest radiograph was obtained during the contact's study., Measurements and Main Results: A total of 1,335 contacts were followed up for 4 years: a smear-positive index case was identified for 937 contacts, of whom 15 developed active tuberculosis and had initially presented with positive tuberculin skin test/QuantiFERON results, a normal chest radiograph, and no symptoms. The positive predictive value was 4% for QuantiFERON and 2% for the tuberculin skin test (when ≥5 mm). The probability of developing active disease was 2.36 times higher with a positive QuantiFERON, and 1.3 times higher with a positive tuberculin skin test. The positive predictive value was 17%, and the positive likelihood ratio was 7.53 for untreated contacts with a positive QuantiFERON. Stratifying according to initial QuantiFERON results showed a 6.36 times higher risk of developing active tuberculosis for patients with a QuantiFERON result greater than or equal to 10 IU/ml. Among bacillus Calmette-Guérin-vaccinated patients, a tuberculin skin test induration greater than or equal to 15 mm correlated better with a positive QuantiFERON., Conclusions: QuantiFERON results were more accurate than tuberculin skin test results in predicting tuberculosis. Although all contacts with QuantiFERON-positive results are at risk of developing tuberculosis, those with a tuberculin skin test induration greater than or equal to 15 mm and QuantiFERON greater than or equal to 10 IU/ml are at highest risk. This has important implications in the clinical management of tuberculosis contacts.

Background: The aim of the study was to assess the correlation between the tuberculin skin test (TST) and in vitro interferon-gamma released assays (IGRAs) with risk factors for the spread of infection in smear positive pulmonary tuberculosis (TB) contacts., Methods: We recruited prospective contacts with smear positive pulmonary TB cases. We looked at human immunodeficiency virus (HIV) infection and other conditions of immunosuppression, presence of BCG vaccination and the degree of exposure to the index case. Patients underwent the TST, chest radiography, sputum analysis when necessary, and IGRA assays (QFN-G-IT and T-SPOT.TB). Presence of cough, diagnostic delay (days between first symptoms and TB diagnostic), contact conditions: room size (square meters) and index of overcrowding (square meters per person) were investigated in the index case., Results: 156 contacts (119 adults, 37 children) of 66 TB patients were enrolled, 2.4 (1-14) contacts per TB case. The positivity of the TST did not correlate with the risk factors studied: presence of cough (p = 0.929); delayed diagnosis (p = 0.244); room size (p = 0.462); overcrowding (p = 0.800). Both QFN-G-IT and T-SPOT.TB, showed significant association with cough (p = 0.001, and p = 0.007) and room size (p = 0.020, and p = 0.023), respectively., Conclusions: Both IGRA associated better than TST with certain host-related risk factors involved in the transmission of disease, such as the presence of cough.

The aim of the present study was to compare the performance of the interferon (IFN)-γ tests (QuantiFERON®-TB Gold In-Tube (QFT-G-IT) and T-SPOT®.TB) with the tuberculin skin test (TST) in diagnosing tuberculosis (TB) infection in children, and to analyse discordant results. This was a prospective study including 98 children from contact-tracing studies and 68 children with TST indurations ≥ 5 mm recruited during public health screenings. Positive IFN-γ tests results were associated with risk of exposure (p<0.0001). T-SPOT.TB was positive in 11 (78.6%) out of 14 cases with active TB and QFT-G-IT in nine (64.3%) out of 14 cases. Sensitised T-cells against Mycobacterium avium were detected in six out of 12 children not vaccinated with bacille Calmette-Guérin (BCG), a TST induration 5-9 mm in diameter and both IFN-γ tests negative. In concordant IFN-γ tests results, a positive correlation was found (p = 0.0001) between the number of responding cells and the amount of IFN-γ released. However, in discordant IFN-γ tests results this correlation was negative (p = 0.371): an increase in the number of spot-forming cells correlated with a decrease in the amount of IFN-γ released. The use of IFN-γ tests is helpful for the diagnosis of TB infection, avoiding cross-reactions with BCG immunisation and nontuberculous mycobacterial infections. The analysis of highly discordant results requires further investigation to elucidate possible clinical implications.

RUTI is a vaccine consisting of Mycobacterium tuberculosis bacilli grown in stress conditions that is fragmented, detoxified and liposomed. RUTI was designed to shorten the treatment of latent tuberculosis infection (LTBI) with isoniazid from 9 months to just 1 month, by additional treatment with two inoculations of RUTI 4 weeks apart. During the validation process for monitoring the immunogenicity of administration of RUTI in a Phase I clinical trial, the question arose whether to introduce the tuberculin skin test (TST) in the screening of non-LTBI volunteers. This study was designed to evaluate the effect of TST on subsequent different T-cell interferon-gamma release assay (TIGRA) responses, using a spectrum of M. tuberculosis-related antigens (ESAT-6, CFP-10, 16 kDa, 19 kDa, MPT64, Ag 85B, 38 kDa, hsp65, PPD and BCG). The results showed an increase in post-TST response even in non-LTBI subjects for most antigens tested, as measured both by whole blood assay (WBA) and ELISPOT. Increased ELISPOT response decreased toward pre-TST levels within 1 month whereas the WBA response did not. Taking into account that there is no definitive correlation between TST and TIGRA tests to diagnose LTBI and the feasibility that TST might alter the immune monitoring included in clinical trials, these data suggest that TST determination should be carefully planned to avoid any interference with TIGRA.