Keiji Mouri

Clinical evaluation of QuantiFERON TB-2G test for immunocompromised patients

The usefulness of the tuberculin skin test (TST) and the QuantiFERON TB-2G (QFT-TB) test were compared in immunocompromised patients. The subjects consisted of 252 immunocompromised patients who were clinically suspected of tuberculosis (TB) infection between April 2005 and December 2006. Regarding the underlying diseases, 74 subjects had malignant diseases, 72 were undergoing immunosuppressive treatment, 52 had diabetes mellitus, 50 had chronic renal failure and four had HIV infection. While the positive rate of the QFT-TB test for the diagnosis of TB infection (TB disease or latent TB infection) was 78.1%, that of TST for TB infection was 50.0%. The QFT-TB test was significantly better than TST. However, 32 (13%) patients had an indeterminate QFT-TB result. Indeterminate findings were significantly more frequent in patients receiving immunosuppressive treatment (28%), especially with lymphocytopaenia in the peripheral blood, than in those who had other underlying diseases. While TST-positive and QFT-TB test-negative results were recognised in immunocompromised patients with bacille Calmette–Guérin vaccination or nontuberculous mycobacterial disease, TST-negative and QFT-TB test-positive results were recognised in immunocompromised patients with a past history of TB infection. It was concluded that the QuantiFERON TB-2G test is a more useful diagnostic method for tuberculosis infection than tuberculin skin test for immunocompromised patients suspected of tuberculosis disease. However, because the results of the QuantiFERON TB-2G test show an indeterminate response for patients receiving immunosuppressive treatment, especially for those with lymphocytopaenia due to severe underlying diseases, care must be taken in the interpretation of the QuantiFERON TB-2G test for these patients.

Clinical Utility of the QuantiFERON TB-2G Test for Elderly Patients With Active Tuberculosis

OBJECTIVE To evaluate the response to the QuantiFERON-TB-2 Gold (QFT-2G) test (Cellestis Ltd; Carnegie, VIC, Australia) in elderly patients with active tuberculosis (TB) to determine whether the QFT-2G test might be a feasible method for diagnosing TB infection in this group of patients. METHODS The subjects were 30 elderly patients with active TB and 100 younger patients with active TB. The QFT-2G test results were analyzed in relation to combined and separate responses to early secretory antigenic target 6-kD (ESAT-6) protein and culture filtrate protein 10 (CFP-10) antigens. RESULTS Of the 30 elderly patients with active TB, 27% had a positive tuberculin skin test (TST) result and 77% had a positive QFT-2G test result. Of the 100 younger patients with active TB, 70% had a positive TST result and 87% had a positive QFT-2G test result. Although there was no significant difference between the two patient groups in the positive rate for the QFT-2G test results (p = 0.185), there was a significant difference in the rates of positive TST results between the elderly and younger patients (p = 0.012). The positive test result rate for both ESAT-6 and CFP-10 antigens in the elderly patients (17%) was significantly lower than that in younger patients (37%; p = 0.038). There was an indeterminate result for the QFT-2G test in five elderly patients, and this might have been related to the presence of lymphocytopenia due to underlying disease. A negative result on the QFT-2G test was detected in two elderly patients, and this might have been related to the severity of the active TB. CONCLUSION We confirmed that the QFT-2G test might be a more useful method of diagnosing TB infection than the TST for elderly patients if peripheral lymphocyte counts have been preserved.

Indeterminate results of QuantiFERON TB-2G test performed in routine clinical practice

The present authors assessed risk factors that can promote indeterminate results of QuantiFERON TB-2G (QFT-2G; Cellestis Ltd, Carnegie, Australia) tests. The subjects were 704 patients with suspected tuberculosis (TB) and latent TB infection between January 2005 and December 2007. The QFT-2G test and the tuberculin skin test (TST) were performed for all subjects. If the results of the QFT-2G test were indeterminate, the test was repeated within 1 month. In total, 72 (10.2%) patients showed indeterminate results on the QFT-2G test. Indeterminate results were due to positive control failure in 68 (88.9%) patients and negative control failure in four patients. The results of the TST were negative for 64 patients showing indeterminate results, the remaining eight patients showed a positive response to the TST. Indeterminate results were significantly associated with elderly and immunocompromised patients. Lymphocytopaenia and hypoalbuminaemia were significantly associated with indeterminate laboratory findings. When the QFT-2G test was repeated for all patients showing indeterminate results, 12 (16.7%) patients demonstrated determinate results on the subsequent test. Indeterminate results of the QuantiFERON TB-2G test under routine clinical practice are not infrequent. When scoring QuantiFERON TB-2G test results for elderly and immunocompromised patients, one must be careful because the possibility of obtaining determinate results may be low even if the test is repeated.

Transitional changes in T-cell responses to Mycobacterium tuberculosis-specific antigens during treatment

BACKGROUND Currently, there is no available test for monitoring the clinical effect of active tuberculosis (TB) disease treatment. Therefore, we studied the usefulness of two commercial IFN-gamma assays (QuantiFERON TB-2G (QFT-2G) and T-SPOT.TB tests) for monitoring clinical efficacy. METHODS The subjects were 40 patients with active TB disease. These two commercial IFN-gamma assays were carried out every three months during active TB disease treatment. RESULTS While the positive response rate of QFT-2G test significantly decreased from 83% at treatment initiation to 58% at treatment completion, that of T-SPOT.TB decreased from 90% at treatment initiation to 63% at treatment completion. Although there was a significant decrease in patients with TB infection showing positive responses for ESAT-6 only or CFP-10 only antigens on both IFN-gamma assays, there was no significant decrease in patients showing positive responses for both ESAT-6 and CFP-10 antigens on both IFN-gamma assays. On both QFT-2G test and T-SPOT.TB test, the mean values of the IFN-gamma levels in the pre- and post-treatment responses showed significantly decreased responses to CFP-10. On the other hand, smear conversion results of clinical specimens were obtained in all patients at treatment completion. CONCLUSIONS Antituberculous treatment induced a significant decrease in T-cell responses to separate ESAT-6 and CFP-10 antigens as measured by both IFN-gamma assays. Although IFN-gamma assays might be later than smear conversion results of clinical specimens, the quantitative responses especially to CFP-10 may be one of the useful monitoring markers of clinical efficacy for active TB disease treatment.

Comparison of T-cell interferon-γ release assays for Mycobacterium tuberculosis-specific antigens in patients with active and latent tuberculosis.

Through the use of QuantiFERON-TB Gold, a commercial IFN-γ assay, we compared differences in quantitative T-cell responses to Mycobacterium tuberculosis (MTB)-specific antigens [QuantiFERON TB-2G (QFT-2G)] between patients with active tuberculosis (TB) disease and those with latent TB infection (LTBI). The patient group consisted of 180 patients with active TB disease (culture-positive for MTB) and 50 screening contacts with LTBI-positive response to the QFT-2G test. We prospectively performed a tuberculin skin test (TST) and a QFT-2G test for all subjects. The median IFN-γ levels upon the application of both antigens, ESAT-6 and CFP-10, were significantly higher in patients with active TB disease than in those with LTBI. A combined positive response to both antigens occurred at a higher rate in patients with active TB disease than in those with LTBI. There were no significant relationships between the quantitative responses of IFN-γ to both antigens and the maximum induration on TST in both patient groups. We demonstrated significant differences in the quantitative responses of IFN-γ to MTB between patients with active TB disease and those with LTBI in this study. However, there was an overlap in the IFN-γ levels between active TB disease and LTBI groups. Therefore, it would be difficult to use the QFT-2G test to completely discriminate active TB disease from LTBI.

QuantiFERON TB-2G test for patients with active tuberculosis stratified by age groups

We evaluated the usefulness of the QuantiFERON TB-2G (QFT-2G) test and the tuberculin skin test (TST) in patients with active tuberculosis (TB) disease stratified by age in 10-year increments. Although the positive rate on TST was over 80% in younger patients aged ≤9 years, it decreased to 55% in patients of aged 70–79 years and 33% in patients aged over 80 years. However, the positive rate on QFT-2G test was over 80% for the age groups between 10–19 and 60–69 years, excluding younger patients aged ≤9 years. Furthermore, the rate was 79% in patients aged 70–79 years and 75% in patients over 80 years of age. The positive response rate of the QFT-2G test was significantly higher than that of the TST in patients over 50 years of age. The indeterminate result of the QFT-2G test increased with age and it is suggested that this result is concerned with the severity of underlying diseases in patients with active TB disease. Although the positive rate on QFT-2G test decreased with age in adults, it is thought to be a useful supportive diagnostic method for active TB disease compared to the TST, except in younger patients aged ≤9 years old.

Clinical evaluation for diagnosing active TB disease and transitional change of two commercial blood tests

We compared the usefulness of TST, QFT-TB and T-SPOT.TB for the identification of patients with active tuberculosis (TB) disease and investigated transitional change in both tests during anti-tuberculous treatment. The subjects were 50 healthy volunteers and 48 patients with active TB disease between October 2005 and December 2006. Among active TB disease patients, 60% had a positive TST result, 81% had a positive QFT-TB result, and 87% had a positive T-SPOT.TB result. Indeterminate results of QFT-TB and T-SPOT.TB were recognized in 12% and 6% of patients, respectively. Negative results on QFT-TB and T-SPOT.TB were 6% each. QFT-TB had a sensitivity of 81% for active TB disease. T-SPOT.TB had a sensitivity of 88% for active TB disease. With regard to transitional changes in QFT-TB results and T-SPOT.TB results, both test results showed a positive response in over 40% of patients 12 months after anti-tuberculous treatment. In conclusion, both blood assays seemed to be more useful than TST for the identification of patients with active TB disease. However, neither of the 2 blood tests appears to provide any certainty regarding the cure of infection.

Clinicopathological analysis of multifocal micronodular pneumocyte hyperplasia associated with tuberous sclerosis in Japan.

Background and objective:  This study investigated the clinical and pathological findings of lung disease in tuberous sclerosis complex (TSC) as previously reported in Japan.

Nutritional deficits in elderly smokers with respiratory symptoms that do not fulfill the criteria for COPD

Background and objective Whereas nutrition deficits are recognized as an expression of systemic inflammation in the elderly with diagnosed chronic obstructive pulmonary disease (COPD), if they occur in symptomatic elderly smokers, unfulfilled COPD criteria are not confirmed. Methods Respiratory function, anthropometry assessment, and diet intake evaluation of 13 COPD patients (COPD group), ten symptomatic elderly smokers (SYSM group), and 27 healthy volunteers (control group) were compared. All were 70 years old or older. Results The SYSM group had lower body weight, body mass index, percentage ideal body weight, body fat percentage, arm muscle circumference, tricep skin fold thickness, serum albumin, prealbumin, and transferrin than the control group and were similar to the COPD group (P < 0.05 each and nonsignificant each). Resting energy expenditure was no different among the groups. Intake of energy, vitamins (A, B1, B2, and C), calcium, iron, fiber, and sodium was also lower in the SYSM group than in the control group (P < 0.05 all) and was similar to the COPD group. Conclusion Elderly smokers who are symptomatic but who do not fulfill the COPD diagnostic criteria have nutritional deficits related to insufficient energy intake that are similar to those seen in COPD patients.

Clinical utility of a T cell‐based assay in the diagnosis of extrapulmonary tuberculosis

Background and objective:  The aim of this study was to evaluate the QuantiFERON TB‐2G (QFT‐2G) results in patients with active extrapulmonary tuberculosis (E‐TB) to determine whether QFT‐2G test might be a reliable diagnostic method for detecting active E‐TB infection compared with the tuberculin skin test (TST).