Performance of commerical blood tests for the diagnosis of latent tuberculosis infection in children and adolescents

BACKGROUND: The accurate diagnosis of latent tuberculosis infection reduces the risk of progression to severe disseminated disease. However, in young children, a major limitation of the standard tuberculin skin test is that false-negative results cannot be detected. The new interferon-gamma release assays QuantiFERON-TB Gold (Cellestis Carnegie Victoria, Australia), QuantiFERON-TB In-Tube (Cellestis), and T-SPOT.TB (Oxford Immunotec, Abingdon, United Kingdom) show promise of greater accuracy, but they may also be affected by impaired cellular immunity, resulting in indeterminate results (ie, insufficient response in positive-control wells).OBJECTIVE:To evaluate the impact of age on the performance of interferon-gamma release assays when used in a routine hospital setting among children tested for suspected active or latent TB infection.METHODS:We retrospectively studied 496 children 0 to 19 years of age who had been tested with the tuberculin skin test and at least 1 interferon-gamma release assay: 181 with QuantiFERON-TB Gold and 315 with QuantiFERON-TB In-Tube. In 154 of the children, paired interferon-gamma release assay testing was available: 87 with QuantiFERON-TB Gold/T-SPOT.TB and 67 with QuantiFERON-TB In-Tube/T-SPOT.TB.RESULTS:Compared with T-SPOT.TB, the rates of indeterminate results were significantly higher for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube. QuantiFERON-TB Gold and QuantiFERON-TB In-Tube also gave indeterminate results more frequently in children /=4 years of age. Indeterminate results were associated with younger age for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube but not for T-SPOT.TB. Considering age as a binary variable (/=4 years of age), a significantly higher concentration of phytohaemagglutinin-produced interferon-gamma was observed in older children with both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube.CONCLUSIONS:Different blood tests for the diagnosis of latent tuberculosis infection in children seem to perform differently, because both QuantiFERON-TB tests were more likely than T-SPOT.TB to give indeterminate results in children <4 years of age

Repeated Quantiferon-TB Gold In-Tube Tests In Routine Clinical Practice: A Five Years Experience

Introduction. Interferon Gamma Release Assays (IGRAs) are increasingly being used as diagnostic aids for Mycobacterium tuberculosis infection. Although evidence on IGRA performance in different populations is quickly accumulating, data on their use in non-experimental settings may provide information on their performance in routine clinical practice. We reviewed the results of QuantiFERON-TB In-Tube (QTF-IT) tests at our hospital since its introduction in diagnostic routine, with particular focus on repeated tests. Methods: We extracted the anonymised electronic records of all consecutive QFT-IT performed at the Laboratory of Microbiology and Virology of University Hospital of Modena (Italy) between May 2006 and December 2010. All tests performed in both inpatients and outpatients were included in the analysis. Results: A total of 10,812 tests were performed in 8,623 individuals (mean age ± SD: 46±23 years; 52.8% male). Among subjects who underwent single testing (n=7,039, 81.6%), 69.7% were negative, 22.5% positive, 7.4% indeterminate and 0.1% not interpretable due to high background in the negative control (0.3% of all tests were not performed due to missing or inadequate samples). In 1,584 (18.4%) subjects (mean age ± SD: 41±23 years; 56.1% male) QFT-IT was repeated at least once: in this group, there was a significantly higher proportion of indeterminate QFT-IT results (11.6%) at first testing, as compared to subjects with single tests (p<0.0001). In most cases (72.5%) the second QFT-IT provided valid concordant results (53.5% concordant negative; 19.0% concordant positive); conversions (from negative to positive) and reversions (from positive to negative) occurred in 3.7% and 7.3% of patients, respectively. Indeterminate results were more likely to become negative instead of positive (7.1% vs. 0.8%; p<0.0001); 3.8% of negative results became indeterminate at second testing. Conclusions: In this non-experimental routine setting, repeated QFT-IT confirmed previous results in most cases, providing little additional clinical information. Indeterminate QFT-IT results were more frequently negative than positive at repeated testing, thus suggesting that most indeterminate tests do not mask a positive result

Performance of commercial blood tests for the diagnosis of latent tuberculosis infection in children and adolescents

BACKGROUND: The accurate diagnosis of latent tuberculosis infection reduces the risk of progression to severe disseminated disease. However, in young children, a major limitation of the standard tuberculin skin test is that false-negative results cannot be detected. The new interferon-gamma release assays QuantiFERON-TB Gold (Cellestis Carnegie Victoria, Australia), QuantiFERON-TB In-Tube (Cellestis), and T-SPOT.TB (Oxford Immunotec, Abingdon, United Kingdom) show promise of greater accuracy, but they may also be affected by impaired cellular immunity, resulting in indeterminate results (ie, insufficient response in positive-control wells).OBJECTIVE: To evaluate the impact of age on the performance of interferon-gamma release assays when used in a routine hospital setting among children tested for suspected active or latent TB infection.METHODS: We retrospectively studied 496 children 0 to 19 years of age who had been tested with the tuberculin skin test and at least 1 interferon-gamma release assay: 181 with QuantiFERON-TB Gold and 315 with QuantiFERON-TB In-Tube. In 154 of the children, paired interferon-gamma release assay testing was available: 87 with QuantiFERON-TB Gold/T-SPOT.TB and 67 with QuantiFERON-TB In-Tube/T-SPOT.TB.RESULTS: Compared with T-SPOT.TB, the rates of indeterminate results were significantly higher for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube. QuantiFERON-TB Gold and QuantiFERON-TB In-Tube also gave indeterminate results more frequently in children &lt;4 years of age than in those &gt;/=4 years of age. Indeterminate results were associated with younger age for both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube but not for T-SPOT.TB. Considering age as a binary variable (&lt;4 and &gt;/=4 years of age), a significantly higher concentration of phytohaemagglutinin-produced interferon-gamma was observed in older children with both QuantiFERON-TB Gold and QuantiFERON-TB In-Tube.CONCLUSION:Different blood tests for the diagnosis of latent tuberculosis infection in children seem to perform differently, because both QuantiFERON-TB tests were more likely than T-SPOT.TB to give indeterminate results in children &lt;4 years of age

Quantiferon-TB Gold In-Tube Tests In Hospital Health Care Workers: A Five Years Experience

Introduction. Interferon Gamma Release Assays (IGRAs) are being largely used worldwide for the screening of tuberculosis infection among subjects likely to undergo multiple testing, such as health care workers (HCW). In theory, IGRAs should overcome the risk of false positive results due to the boosting effect, at difference with the in vivo tuberculin skin test. Evaluation of IGRA results in HCW in a non-experimental setting over several years may provide information on the real-life performance of these tests in daily practice. We reviewed the results of QuantiFERON-TB In-Tube (QTF-IT) tests performed on HCW over nearly five years, with particular focus on repeated tests. Methods: We extracted the anonymised electronic records of all consecutive QFT-IT performed on HCW between May 2006 and December 2010. All tests were done at the Laboratory of Microbiology and Virology of University Hospital of Modena (Italy). Results: A total of 1,531 tests were performed in 1,189 individuals (mean age ± SD: 37±10 years; 29% male). In 226 subjects (37±9 years; 31% male) QFT-IT was repeated at least once. Among subjects who underwent single testing (n=963, 81%), 85% were negative and 14% positive, as compared to the results at first test among subjects with repeated tests (69% negative, 27% positive; p<0.0001). In the majority of cases (84%) a second QFT-IT provided a concordant valid result. Reversion (from positive to negative) occurred more frequently than conversion (from negative to positive) (respectively, 10% vs. 4% of repeated tests). Rate of indeterminate results was extremely low, 0.4% in subjects with single testing and 1.8% at first test in subjects with multiple tests. At second testing, indeterminate QFT-IT results at first testing became negative in all but one case, which remained indeterminate. Conclusions: In this non-experimental routine setting of tuberculosis infection screening in HCW, subjects who underwent repeated tests were more likely to have a positive QFT-IT at first testing, as compared to subjects with single testing. However, a repeated QFT-IT confirmed previous results in almost all cases. Reversions occurred more often than conversions. Rate of indeterminate QFT-IT results was extremely low, thus indicating a very good technical performance of this test in HCW in a low TB prevalence area

Routine hospital use of a new commercial whole blood interferon-gamma assay for the diagnosis of tuberculosis infection

Rationale: Interferon (IFN)-? blood tests may improve the current level of diagnostic accuracy for tuberculosis infection. The QuantiFERON-TB Gold (QFT-Gold) has been used in selected populations and shows higher specificity than the tuberculin skin test (TST). Objective: To evaluate the QFT-Gold test in unselected patients and assess the level of agreement with the TST. Methods: The test has been routinely performed on whole blood samples in our microbiology laboratory for 8 months. Demographic, clinical, and microbiological data have been collected and correlated to the QFT-Gold results. Measurements and Main Results: Of 318 patients tested, 68 (21.4%) gave an indeterminate (low positive mitogen control) QFT-Gold result. Indeterminate results were significantly overrepresented in patients with a negative TST (28.9% vs. 6.6% in TST-positive patients; p &lt; 0.0001, ?2 test) and were more frequent in patients receiving immunosuppressive therapies than in those who were not receiving such treatments (odds ratio, 3.35; 95% confidence interval, 1.84–6.08; p &lt; 0.0001). After excluding indeterminate results, the concordance between QFT-Gold and TST was significantly lower in Bacille Calmette-Guérin–vaccinated individuals (41.5%) than in nonvaccinated individuals (80.3%) (p &lt; 0.0001). In 11 patients with active tuberculosis (5 culture-confirmed), QFT-Gold provided more positive results than the TST (66.7% vs. 33.3%; p = 0.165). Conclusions: The QFT-Gold test is feasible in routine hospital use for the diagnosis of tuberculosis infection. As with the TST, immunosuppression may negatively affect the test's performance, with a significant rate of indeterminate results in the most vulnerable population

Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study

BackgroundTwo commercial blood assays for the diagnosis of latent tuberculosis infection—T-SPOT.TB and QuantiFERON-TB Gold—have been separately compared with the tuberculin skin test. Our aim was to compare the efficacy of all three tests in the same population sample.MethodsWe did a prospective study in 393 consecutively enrolled patients who were tested simultaneously with T-SPOT.TB and QuantiFERON-TB Gold because of suspected latent or active tuberculosis. 318 patients also had results available for a tuberculin skin test.FindingsOverall agreement with the skin test was similar (T-SPOT.TB ?=0·508, QuantiFERON-TB Gold ?=0·460), but fewer BCG-vaccinated individuals were identified as positive by the two blood assays than by the tuberculin skin test (p=0·003 for T-SPOT.TB and p&lt;0.0001 for QuantiFERON-TB Gold). Indeterminate results were significantly more frequent with QuantiFERON-TB Gold (11%, 43 of 383) than with T-SPOT.TB (3%, 12 of 383; p&lt;0·0001) and were associated with immunosuppressive treatments for both tests. Age younger than 5 years was significantly associated with indeterminate results with QuantiFERON-TB Gold (p=0.003), but not with T-SPOT.TB. Overall, T-SPOT.TB produced significantly more positive results (38%, n=144, vs 26%, n=100, with QuantiFERON-TB Gold; p&lt;0·0001), and close contacts of patients with active tuberculosis were more likely to be positive with T-SPOT.TB than with QuantiFERON-TB Gold (p=0·0010).InterpretationT-SPOT.TB and QuantiFERON-TB Gold have higher specificity than the tuberculin skin test. Rates of indeterminate and positive results, however, differ between the blood tests, suggesting that they might provide different results in routine clinical practice

Comparison of three assays currently used for diagnosis of legionellosis

The laboratory diagnosis of Legionnaires’ disease is extremely complex due to the difficulty of isolating and identifying the etiological agent in a short time and also for the frequent late appearance of antibodies. For this reason it should use not only the cultures but also other diagnostic tests such as urinary antigen and antibody research. Our study evaluated the performance of these methods.We calculated the positive predictive value (PPV) and negative predictive value (NPV), sensitivity and specificity of each test

Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study

BACKGROUND: Two commercial blood assays for the diagnosis of latent tuberculosis infection--T-SPOT.TB and QuantiFERON-TB Gold--have been separately compared with the tuberculin skin test. Our aim was to compare the efficacy of all three tests in the same population sample. METHODS: We did a prospective study in 393 consecutively enrolled patients who were tested simultaneously with T-SPOT.TB and QuantiFERON-TB Gold because of suspected latent or active tuberculosis. 318 patients also had results available for a tuberculin skin test. FINDINGS: Overall agreement with the skin test was similar (T-SPOT.TB kappa=0.508, QuantiFERON-TB Gold kappa=0.460), but fewer BCG-vaccinated individuals were identified as positive by the two blood assays than by the tuberculin skin test (p=0.003 for T-SPOT.TB and p&lt;0.0001 for QuantiFERON-TB Gold). Indeterminate results were significantly more frequent with QuantiFERON-TB Gold (11%, 43 of 383) than with T-SPOT.TB (3%, 12 of 383; p&lt;0.0001) and were associated with immunosuppressive treatments for both tests. Age younger than 5 years was significantly associated with indeterminate results with QuantiFERON-TB Gold (p=0.003), but not with T-SPOT.TB. Overall, T-SPOT.TB produced significantly more positive results (38%, n=144, vs 26%, n=100, with QuantiFERON-TB Gold; p&lt;0.0001), and close contacts of patients with active tuberculosis were more likely to be positive with T-SPOT.TB than with QuantiFERON-TB Gold (p=0.0010). INTERPRETATION: T-SPOT.TB and QuantiFERON-TB Gold have higher specificity than the tuberculin skin test. Rates of indeterminate and positive results, however, differ between the blood tests, suggesting that they might provide different results in routine clinical practice