Specificity of a whole blood IGRA in German nursing students

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma release assays (IGRA) are used for tuberculosis (TB) screening in healthcare workers (HCWs). However, data on specificity of IGRA in serial testing of HCWs is sparse. Therefore the specificity and the negative predictive value of the IGRA - QuantiFERON-TB Gold In-Tube (QFT) - in German nursing students was investigated.</p> <p>Methods</p> <p>194 nursing students at the start of their professional career were tested with the QFT. 14 nursing students were excluded from the specificity analysis, due to exposure to mycobacterium tuberculosis. Two of these subjects were QFT- positive. None of them developed disease during the year of follow-up. A study group of 180 students, all with very low risk of prior TB infection, remained in the specificity analysis. Subjects were monitored for at least two years with respect to the development of active TB disease. IGRA was performed at the start of the training and after one year.</p> <p>Results</p> <p>The mean age of the study group (n = 180) was 23 years (range 18-53) with 70.9% female and 99.4% German born. The specificity of QFT was 98.9% (178/180; 95% CI 0.96-0.99); lowering the cut-off from 0.35 IU/ml to 0.1 IU/ml would have decreased specificity only slightly to 97.8% (176/180; 95% CI 0.94-0.99). Of the 154 nursing students available for re-testing, one student who initially scored positive reverted to negative, and one student initially negative converted to positive. None of the monitored group with initially negative QFT results developed TB disease, indicating a high negative predictive value of the IGRA in this population.</p> <p>Conclusions</p> <p>Following our data, QFT can serve as an effective tool in pre-employment TB screenings for HCWs. As its negative results were stable over time, specificity of the QFT in serial testing of HCWs is high. As the risk of acquiring TB infection in the German healthcare system appears to be low, our data supports the recommendation of performing TB screening only in those HCWs with known contact to TB patients or infectious materials.</p

Predictors of persistently positive Mycobacterium-tuberculosis-specific interferon-gamma responses in the serial testing of health care workers

<p>Abstract</p> <p>Background</p> <p>Data on the performance of Mycobacterium-tuberculosis-specific interferon-(IFN)-γ release assays (IGRAs) in the serial testing of health care workers (HCWs) is limited. The objective of the present study was to determine the frequency of IGRA conversions and reversions and to identify predictors of persistent IGRA positivity among serially tested German HCWs in the absence of recent extensive tuberculosis (TB) exposure.</p> <p>Methods</p> <p>In this observational cohort-study HCWs were prospectively recruited within occupational safety and health measures and underwent a tuberculin skin test (TST) and the IGRA QuantiFERON^®-TB Gold In-Tube (QFT-GIT) at baseline. The QFT-GIT was repeated 18 weeks later in the median. QFT-GIT conversions (and reversions) were defined as baseline IFN-γ < 0.35 IU/ml and follow-up IFN-γ ≥ 0.35 IU/ml (and vice versa). Predictors of persistently positive QFT-GIT results were calculated by logistic regression analysis.</p> <p>Results</p> <p>In total, 18 (9.9%) and 15 (8.2%) of 182 analyzed HCWs were QFT-GIT-positive at baseline and at follow-up, respectively. We observed a strong overall agreement between baseline and follow-up QFT-GIT results (κ = 0.70). Reversions (6/18, 33.3%) occurred more frequently than conversions (3/162, 1.9%). Age and positive prior and recent TST results independently predicted persistent QFT-GIT positivity. Furthermore, the chance of having persistently positive QFT-GIT results raised about 3% with each additional 0.1 IU/ml increase in the baseline IFN-γ response (adjusted odds ratio 1.03, 95% confidence interval 1.01-1.04). No active TB cases were detected within an observational period of more than two years.</p> <p>Conclusions</p> <p>The QFT-GIT's utility for the application in serial testing was limited by a substantial proportion of reversions. This shortcoming could be overcome by the implementation of a borderline zone for the interpretation of QFT-GIT results. However, further studies are needed to clearly define the within-subject variability of the QFT-GIT and to confirm that increasing age, concordantly positive TST results, and the extend of baseline IFN-γ responses may predict the persistence of QFT-GIT positivity over time in serially tested HCWs with only a low or medium TB screening risk in a TB low-incidence setting.</p

T-cell-based diagnosis of tuberculosis infection in children in Lithuania: a country of high incidence despite a high coverage with bacille Calmette-Guerin vaccination

<p>Abstract</p> <p>Background</p> <p>Lithuania is a country with a high incidence of tuberculosis (TB), despite a high coverage with bacille Calmette-Guerin (BCG) vaccination. Until now the only method used to detect latent TB infection was the tuberculin skin test (TST). However, TST may have a cross reactivity to the BCG vaccine and to environmental mycobacteria. The aim of this study was to conduct assessments of the diagnostic accuracy of the T-cell based test (T SPOT TB) for TB in children who had previously been BCG vaccinated and compare these with the results of the TST.</p> <p>Methods</p> <p>Between January 2005 and February 2007, children with bacteriologically confirmed TB, children having contacts with a case of infectious pulmonary TB and children without any known risk for TB were tested with both the TST and T SPOT TB.</p> <p>Results</p> <p>The TST and T SPOT TB tests were positive for all patients in the „culture-confirmed TB“ group. Whereas, in the „high risk for TB“ group, the TST was positive for 60%, but the T SPOT TB test, only for 17.8%. Meanwhile the results for the „low risk for TB“ group were 65.4% and 9.6%, respectively. A correlation between the TST and T SPOT TB was obtained in the "culture-confirmed TB" group where the TST ≥15 mm (r = 0.35, p < 0.001).</p> <p>Conclusion</p> <p>The T-cell based method is more objective than the TST for identifying latent TB infection in children who had been previously BCG vaccinated. This method could be useful in countries like Lithuania where there is a high incidence of TB despite a high coverage with BCG vaccination. It may also help to avoid unnecessary chemoprophylaxis when TST reactions are false-positive.</p

School based screening for tuberculosis infection in Norway: comparison of positive tuberculin skin test with interferon-gamma release assay

<p>Abstract</p> <p>Background</p> <p>In Norway, screening for tuberculosis infection by tuberculin skin test (TST) has been offered for several decades to all children in 9th grade of school, prior to BCG-vaccination. The incidence of tuberculosis in Norway is low and infection with <it>M. tuberculosis </it>is considered rare. QuantiFERON^®TB Gold (QFT) is a new and specific blood test for tuberculosis infection. So far, there have been few reports of QFT used in screening of predominantly unexposed, healthy, TST-positive children, including first and second generation immigrants. In order to evaluate the current TST screening and BCG-vaccination programme we aimed to (1) measure the prevalence of QFT positivity among TST positive children identified in the school based screening, and (2) measure the association between demographic and clinical risk factors for tuberculosis infection and QFT positivity.</p> <p>Methods</p> <p>This cross-sectional multi-centre study was conducted during the school year 2005–6 and the TST positive children were recruited from seven public hospitals covering rural and urban areas in Norway. Participation included a QFT test and a questionnaire regarding demographic and clinical risk factors for latent infection. All positive QFT results were confirmed by re-analysis of the same plasma sample. If the confirmatory test was negative the result was reported as non-conclusive and the participant was offered a new test.</p> <p>Results</p> <p>Among 511 TST positive children only 9% (44) had a confirmed positive QFT result. QFT positivity was associated with larger TST induration, origin outside Western countries and known exposure to tuberculosis. Most children (79%) had TST reactions in the range of 6–14 mm; 5% of these were QFT positive. Discrepant results between the tests were common even for TST reactions above 15 mm, as only 22 % had a positive QFT.</p> <p>Conclusion</p> <p>The results support the assumption that factors other than tuberculosis infection are widely contributing to positive TST results in this group and indicate the improved specificity of QFT for latent tuberculosis. Our study suggests a very low prevalence of latent tuberculosis infection among 9th grade school children in Norway. The result will inform the discussion in Norway of the usefulness of the current TST screening and BCG-policy.</p

Within-Subject Variability of Interferon-g Assay Results for Tuberculosis and Boosting Effect of Tuberculin Skin Testing: A Systematic Review

Background: Variability in interferon-gamma release assays (IGRAs) results for tuberculosis has implications for interpretation of results close to the cut-point, and for defining thresholds for test conversion and reversion. However, little is known about the within-subject variability (reproducibility) of IGRAs. Several national guidelines recommend a twostep testing procedure (tuberculin skin test [TST] followed by IGRA) for the diagnosis of LTBI. However, the effect of a preceding TST on subsequent IGRA results has been reported in studies with apparently conflicting results. Methodology/Findings: We conducted a systematic review to synthesize evidence on within-subject variability of IGRA results and the potential boosting effect of TST. We searched several databases and reviewed citations of previous reviews on IGRAs. We included studies using commercial IGRAs, in addition to non-commercial versions of the ELISPOT assay. Four studies, fulfilling our predefined criteria, examined within-subject variability and 13 studies evaluated TST effects on subsequent IGRA responses. Meta-analysis was not considered appropriate because of heterogeneity in study methods, assays, and populations. Although based on limited data, within-subject variability was present in all studies but the magnitude varied (16-80%) across studies. A TST induced ‘‘boosting’ ’ of IGRA responses was demonstrated in several studies and although more pronounced in IGRA-positive (i.e. sensitized) individuals, also occurred in a smaller but not insignificant proportion of IGRA-negative subjects. The TST appeared to affect IGRA responses only after 3 days and may apparentl

Rapid Changes in the Light/Dark Cycle Disrupt Memory of Conditioned Fear in Mice

Background: Circadian rhythms govern many aspects of physiology and behavior including cognitive processes. Components of neural circuits involved in learning and memory, e.g., the amygdala and the hippocampus, exhibit circadian rhythms in gene expression and signaling pathways. The functional significance of these rhythms is still not understood. In the present study, we sought to determine the impact of transiently disrupting the circadian system by shifting the light/ dark (LD) cycle. Such ‘‘jet lag’ ’ treatments alter daily rhythms of gene expression that underlie circadian oscillations as well as disrupt the synchrony between the multiple oscillators found within the body. Methodology/Principal Findings: We subjected adult male C57Bl/6 mice to a contextual fear conditioning protocol either before or after acute phase shifts of the LD cycle. As part of this study, we examined the impact of phase advances and phase delays, and the effects of different magnitudes of phase shifts. Under all conditions tested, we found that recall of fear conditioned behavior was specifically affected by the jet lag. We found that phase shifts potentiated the stress-evoked corticosterone response without altering baseline levels of this hormone. The jet lag treatment did not result in overall sleep deprivation, but altered the temporal distribution of sleep. Finally, we found that prior experience of jet lag helps to compensate for the reduced recall due to acute phase shifts. Conclusions/Significance: Acute changes to the LD cycle affect the recall of fear-conditioned behavior. This suggests that