IFN-γ/TNF-α ratio in response to immuno proteomically identified human T-cell antigens of Mycobacterium tuberculosis - The most suitable surrogate biomarker for latent TB infection.

The enormous reservoir of latent TB infection (LTBI) poses a major hurdle for global TB control. The existing Tuberculin skin test (TST) and IFN-γ release assays (IGRAs) are found to be suboptimal for LTBI diagnosis. Previously we had taken an immunoproteomic approach and identified 10 protein fractions (contains 16 proteins), which are solely recognized by LTBI. In a cohort of 40 pulmonary TB patients (PTB) and 35 healthy household contacts (HHC), IFN-γ and TNF-α response were measured against 16 antigens by using 1:10 diluted whole blood assay. Among all the antigens, IFN-γ response to Rv2626c has shown positivity of 88.57% in HHC and 7.5% in PTB group. IFN-γ response to combination of Rv2626c + Rv3716c has demonstrated 100% positivity in HHC and 17.5% positivity in PTB respectively. Compared to individual cytokines (i.e. IFN-γ and TNF-α), ratio of IFN-γ/TNF-α has shown promising results for diagnosis of LTBI. IFN-γ/TNF-α ratio against Rv3716c and TrxC has exhibited a positivity of 94.29% in HHC and 5% in PTB group. Accession of Rv2626c and Rv3716c may improve the diagnostic performance of existing QFT-GIT. Independent of QFT-GIT assay, ratio of IFN-γ/TNF-α in response to either Rv3716c or TrxC may acts as suitable surrogate biomarker for LTBI.

Quantiferon TB-Gold conversion can predict active tuberculosis development in elderly nursing home residents.

AIM: The study was carried out on elderly nursing home residents in Taiwan. We assessed whether the serial QuantiFERON-TB Gold (QFT-G) assay and serial tuberculin skin test (TST) were reliable tools to predict or exclude the development of active tuberculosis (TB). METHODS: This prospective observational cohort study involved non-bacillus Calmette-Guérin-vaccinated 259 elderly nursing home residents free of active TB at baseline. Of these, 147 were eligible for follow up. Participants underwent serial QFT-G and TST at baseline and 2-year follow up, and were monitored for active TB over 5 years. Agreement between QFT-G and TST, incidence rate ratio, positive predictive value, and negative predictive value for progression to active TB were measured. RESULTS: During 5-year follow up, three participants developed active TB. The agreement between these two tests was 54.13% (ĸ = 0.167, P = 0.001). The incidence rate ratio was 15.8 (P = 0.016) for the QFT-G-conversion group compared with the TST-positive group at baseline. Positive predictive value for QFT-G conversion groups was 25%. Negative predictive value was 100% for the TST-negative group at baseline. CONCLUSION: In the elderly nursing home residents, QFT-G conversion is a more reliable tool to predict the development of active TB. Meanwhile, TST is a valuable tool for predicting the chance of not developing active TB.

Clinical Significance of Interferon gamma Release Assay for Diagnosis of Tuberculosis in Children / 소아감염

PURPOSE: The purpose of this study is to evaluate the usefulness and limitation of QuantiFERON-TB Gold (QTB) for diagnosis of latent tuberculosis in children. METHODS: The medical records of 112 children who were tested by tuberculin skin test (TST) and QTB for detection of latent tuberculosis (TB) in Eulji General Hospital during the period from January 2007 to June 2009 were retrospectively reviewed. RESULTS: Of the 112 participants, the clinical TB group included 15 (13.4%), the contact group included 43 (38.4%), and the non-contact group included 54 (48.2%). Positive rates of TST and QTB were 100% and 80% in the clinical TB group, 64% and 14% in the close contact group, 27% and 0% in the casual contact group, and 52% and 2% in the non-contact group, respectively. Sensitivity of QTB was 80.0% and specificity was 92.6%. Agreement between QTB and TST was poor (kappa=0.209). We also confirmed that the positive rate of QTB increased as the age of the patient increased (P=0.011). A QTB indeterminate result was observed in 11 (9.8%) subjects. QTB was retested in 15 subjects. In 5 of the 6 subjects who had positive results initially, positive results persisted for a median 2.2 months after termination of treatment. CONCLUSION: Although QTB was associated with several problems, including low sensitivity and a high rate of indeterminate results, it had clinical importance due to its high specificity. We found good correlation with regard to exposure and QTB positivity, including that of young children under 5 years of age. However, clinical application of interferon-gamma releasing assay for young children for diagnosis of active and latent tuberculosis will require additional prospective studies.

Tuberculin Skin Test and QuantiFERON-TB Gold Assay before and after Treatment for Latent Tuberculosis Infection among Health Care Workers in Local Tertiary Hospital / 결핵및호흡기질환

BACKGROUND: The QuantiFERON-TB Gold assay and tuberculin skin test (TST) have been useful test for diagnosing latent tuberculosis infections (LTBI). However, there are few reports on the efficacy of the QuantiFERON-TB Gold assay and TST in evaluating the response after the treatment of LTBI. This study examined the changes in the TST and QuantiFERON-TB Gold assay before and after a treatment for latent tuberculosis in health care workers (HCWs) at a local tertiary hospital. METHODS: A cohort of volunteers working as nurses and doctors who underwent a TST and QuantiFERON-TB Gold assay was established. The volunteers positive for the QuantiFERON-TB Gold assay had been treated with 3 months of isoniazid (INH) and rifampin (RFP). After completing treatment, the TST and QuantiFERON-TB Gold assay were repeated. RESULTS: Of the 48 participants (14 doctors, 34 nurses, M: F=11:37, mean age=29.9+/-5.5 years, mean employment period=74.9+/-64.3 months), 19 (39.6%) tested positive to the TST (mean induration=19.1+/-9.7 mm) and 8 (16.7%) were QuantiFERON-TB Gold assay. Among them, one had active pulmonary tuberculosis. Seven volunteers were consistently positive to both the TST and QuantiFERON-TB Gold assay after being medicated with INH and RFP for 3 months. CONCLUSION: TST and QuantiFERON-TB Gold assay are unsuitable for evaluating the treatment response of LTBI because they were consistently positive both before and after the anti-tuberculosis medication.