Background: Current immunodiagnostic tests for tuberculosis (TB) are based on the detection of an immune response toward mycobacterial antigens injected into the skin or following an in-vitro simulation in interferon gamma-release assays. Both tests have limited sensitivity and are unable to differentiate between tuberculosis infection (LTBI) and active tuberculosis disease (aTB). To overcome this, the use of novel Mycobacterium tuberculosis (M. tuberculosis) stage-specific antigens for the diagnosis of LTBI and aTB has gained interest in recent years. This review summarizes current evidence on novel antigens used for the immunodiagnosis of tuberculosis and discrimination of LTBI and aTB. In addition, results on measured biomarkers after stimulation with novel M. tuberculosis antigens were also reviewed.Methods: A systematic literature review was performed in Pubmed, EMBASE and web of science searching articles from 2000 up until December 2017. Only articles reporting studies in humans using novel antigens were included.Results: Of 1,533 articles screened 34 were included in the final analysis. A wide range of novel antigens expressed during different stages and types of LTBI and aTB have been assessed. M. tuberculosis antigens Rv0081, Rv1733c, Rv1737c, Rv2029c, Rv2031 and Rv2628, all encoded by the dormancy of survival regulon, were among the most widely studied antigens and showed the most promising results. These antigens have been shown to have best potential for differentiating LTBI from aTB. In addition, several studies have shown that the inclusion of cytokines other than IFN-γ can improve sensitivity.Conclusion: There is limited evidence that the inclusion of novel antigens as well as the measurement of other biomarkers than IFN-γ may improve sensitivity and may lead to a discrimination of LTBI from aTB.

Background: Interferon-gamma release assays (IGRA) are well-established immunodiagnostic tests for tuberculosis (TB) in adults. In children these tests are associated with higher rates of false-negative and indeterminate results. Age is presumed to be one factor influencing cytokine release and therefore test performance. The aim of this study was to systematically review factors associated with indeterminate IGRA results in pediatric patients. Methods: Systematic literature review guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) searching PubMed, EMBASE, and Web of Science. Studies reporting results of at least one commercially available IGRA (QuantiFERON-TB, T-SPOT.TB) in pediatric patient groups were included. Random effects meta-analysis was used to assess proportions of indeterminate IGRA results. Heterogeneity was assessed using the I 2 value. Risk differences were calculated for studies comparing QuantiFERON-TB and T-SPOT.TB in the same study. Meta-regression was used to further explore the influence of study level variables on heterogeneity. Results: Of 1,293 articles screened, 133 studies were included in the final analysis. These assessed QuantiFERON-TB only in 77.4% (103/133), QuantiFERON-TB and T-SPOT.TB in 15.8% (21/133), and T-SPOT.TB only in 6.8% (9/133) resulting in 155 datasets including 107,418 participants. Overall 4% of IGRA results were indeterminate, and T-SPOT.TB (0.03, 95% CI 0.02–0.05) and QuantiFERON-TB assays (0.05, 95% CI 0.04–0.06) showed similar proportions of indeterminate results; pooled risk difference was−0.01 (95% CI −0.03 to 0.00). Significant differences with lower proportions of indeterminate assays with T-SPOT.TB compared to QuantiFERON-TB were only seen in subgroup analyses of studies performed in Africa and in non-HIV-infected immunocompromised patients. Meta-regression confirmed lower proportions of indeterminate results for T-SPOT.TB compared to QuantiFERON-TB only among studies that reported results from non-HIV-infected immunocompromised patients ( p < 0.001). Conclusion: On average indeterminate IGRA results occur in 1 in 25 tests performed. Overall, there was no difference in the proportion of indeterminate results between both commercial assays. However, our findings suggest that in patients in Africa and/or patients with immunocompromising conditions other than HIV infection the T-SPOT.TB assay appears to produce fewer indeterminate results.

The impact of the introduction and advancement in communication technology in recent years on exposure level of the population is largely unknown. The main aim of this study is to systematically review literature on the distribution of radiofrequency electromagnetic field (RF-EMF) exposure in the everyday environment in Europe and summarize key characteristics of various types of RF-EMF studies conducted in the European countries. We systematically searched the ISI Web of Science for relevant literature published between 1 January 2000 and 30 April 2015, which assessed RF-EMF exposure levels by any of the methods: spot measurements, personal measurement with trained researchers and personal measurement with volunteers. Twenty-one published studies met our eligibility criteria of which 10 were spot measurements studies, 5 were personal measurement studies with trained researchers (microenvironmental), 5 were personal measurement studies with volunteers and 1 was a mixed methods study combining data collected by volunteers and trained researchers. RF-EMF data included in the studies were collected between 2005 and 2013. The mean total RF-EMF exposure for spot measurements in European "Homes" and "Outdoor" microenvironments was 0.29 and 0.54 V/m, respectively. In the personal measurements studies with trained researchers, the mean total RF-EMF exposure was 0.24 V/m in "Home" and 0.76 V/m in "Outdoor". In the personal measurement studies with volunteers, the population weighted mean total RF-EMF exposure was 0.16 V/m in "Homes" and 0.20 V/m in "Outdoor". Among all European microenvironments in "Transportation", the highest mean total RF-EMF 1.96 V/m was found in trains of Belgium during 2007 where more than 95% of exposure was contributed by uplink. Typical RF-EMF exposure levels are substantially below regulatory limits. We found considerable differences between studies according to the type of measurements procedures, which precludes cross-country comparison or evaluating temporal trends. A comparable RF-EMF monitoring concept is needed to accurately identify typical RF-EMF exposure levels in the everyday environment.