Diagnostic Accuracy of Interferon Gamma-Induced Protein 10 mRNA Release Assay for Tuberculosis.

Interferon gamma (IFN-γ) release assays (IGRAs) are increasingly used to test for latent tuberculosis (TB) infection. Although highly specific, IGRAs have a relatively high false-negative rate in active TB patients. A more sensitive assay is needed. IFN-γ-induced protein 10 (IP-10) is an alternative biomarker with a 100-fold-higher expression level than IFN-γ, allowing for different analysis platforms, including molecular detection. The PCR technique is already an integrated tool in most TB laboratories and, thus, an obvious platform to turn to. In this case-control study, we investigated the diagnostic sensitivity and specificity of a molecular assay detecting IP-10 mRNA expression following antigen stimulation of a blood sample. We included 89 TB patients and 99 healthy controls. Blood was drawn in QuantiFeron-TB gold in-tube (QFT) assay tubes. Eight hours poststimulation, IP-10 mRNA expression was analyzed, and 20 h poststimulation, IP-10 and IFN-γ protein plasma levels were analyzed using an in-house IP-10 enzyme-linked immunosorbent assay (ELISA) and the official QFT ELISA, respectively. The IP-10 mRNA assay provided high specificity (98%), sensitivity (80%), and area under the concentration-time curve (AUC) (0.97); however, the QFT assay provided a higher overall diagnostic potential, with specificity of 100%, sensitivity of 90%, and AUC of 0.99. The IP-10 protein assay performed on par with the QFT assay, with specificity of 98%, sensitivity of 87%, and AUC of 0.98. We have provided proof of high technical performance of a molecular assay detecting IP-10 mRNA expression. As a diagnostic tool, this assay would gain from further optimization, especially on the kinetics of IP-10 mRNA expression.

Correlation between tuberculin skin test and IGRAs with risk factors for the spread of infection in close contacts with sputum smear positive in pulmonary tuberculosis.

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.

Predicting the Development of Tuberculosis with the Tuberculin Skin Test and QuantiFERON Testing.

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.