Interferon-γ release assays (IGRAs) are now established for the immunodiagnosis of latent infection with Mycobacterium tuberculosis in many countries. However, the role of IGRAs for the diagnosis of active tuberculosis (TB) remains unclear. Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and quality assessment of diagnostic accuracy studies (QUADAS) guidelines, we searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-November 2009 that evaluated the evidence of using QuantiFERON-TB® Gold in-tube (QFT-G-IT) and T-SPOT.TB® directly on blood or extrasanguinous specimens for the diagnosis of active TB. The literature search yielded 844 studies and 27 met the inclusion criteria. In blood and extrasanguinous fluids, the pooled sensitivity for the diagnosis of active TB was 80% (95% CI 75-84%) and 48% (95% CI 39-58%) for QFT-G-IT, and 81% (95% CI 78-84%) and 88% (confirmed and unconfirmed cases) (95% CI 82-92%) for T-SPOT.TB®, respectively. In blood and extrasanguinous fluids, the pooled specificity was 79% (95% CI 75-82%) and 82% (95% CI 70-91%) for QFT-G-IT, and 59% (95% CI 56-62%) and 82% (95% CI 78-86%) for T-SPOT.TB®, respectively. Although the diagnostic sensitivities of both IGRAs were higher than that of tuberculin skin tests, it was still not high enough to use as a rule out test for TB. Positive evidence for the use of IGRAs in compartments other than blood will require more independent and carefully designed prospective studies.

Author Contributions: M.S. made a substantial contribution to the conception and design of the work and to the acquisition, analysis, and interpretation of data for the work; wrote the manuscript; critically revised the manuscript for important intellectual content; and gave final approval of the current version to be published. F.v.L. made a substantial contribution to the conception and design of the work and to the interpretation of data for the work, performed statistical analysis, wrote the manuscript, critically revised the manuscript for important intellectual content, and gave final approval of the current version to be published. P.R. made a substantial contribution to the conception and design of the work and to the interpretation of data for the work, critically revised the manuscript for important intellectual content, and gave final approval of the current version to be published. C.L. made a substantial contribution to the conception and design of the work and to the acquisition, analysis, and interpretation of data for the work; wrote the manuscript; critically revised the manuscript for important intellectual content; and gave final approval of the current version to be published. All other authors made a contribution to the acquisition of the data for the work, critically revised the manuscript for important intellectual content, and gave final approval of the current version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Rationale: The rapid diagnosis of pulmonary tuberculosis (TB) is difficult when acid fast bacilli (AFB) cannot be detected in sputum smears. Objectives: Following a proof of principle study, we examined in routine clinical practice whether individuals with sputum AFB smearnegative TB can be discriminated from those with latent TB infection by local immunodiagnosis with a Mycobacterium tuberculosis-specific enzyme-linked immunospot (ELISpot) assay. Methods: Subjects suspected of having active TB who were unable to produce sputum or with AFB-negative sputum smears were prospectively enrolled at Tuberculosis Network European Trialsgroup centers in Europe. ELISpot with early-secretory-antigenic-target-6 and culture-filtrate-protein-10 peptides was performed on peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage mononuclear cells (BALMCs). M. tuberculosis-specific nucleic acid amplification (NAAT) was performed on bronchoalveolar lavage fluid. Measurements and Main Results: Seventy-one of 347 (20.4%) patients had active TB. Out of 276 patients who had an alternative diagnosis, 127 (46.0%) were considered to be latently infected with M. tuberculosis by a positive PBMC ELISpot result. The sensitivity and specificity of BALMC ELISpot for the diagnosis of active pulmonary TB were 91 and 80%, respectively. The BALMC ELISpot (diagnostic odds ratio [OR], 40.4) was superior to PBMC ELISpot (OR, 10.0), tuberculin skin test (OR, 7.8), and M. tuberculosis specific NAAT (OR, 12.4) to diagnose sputum AFB smear-negative TB. In contrast to PBMC ELISpot and tuberculin skin test, the BALMC ELISpot was not influenced by previous history of TB. Conclusions: Bronchoalveolar lavage ELISpot is an important advancement to rapidly distinguish sputum AFB smear-negative TB from latent TB infection in routine clinical practice.Tuberculosis (TB) is among the leading causes of morbidity and mortality worldwide (1). Pulmonary TB is the major manifestation of the disease (2). Despite constant diagnostic improvements, the rapid diagnosis of pulmonary TB is still difficult in a substantial proportion of cases (3). Identification of Mycobacterium tuberculosis by culture is the diagnostic gold standard for active TB, but culture growth of M. tuberculosis may take 2 or more weeks on average (4), and its sensitivity is only approximately 80% (5).Microscopy for the identification of acid-fast bacilli (AFB) is rapid and inexpensive (6), but AFB are undetectable from the sputum smear in 85 to 90% of children (7) and in approximately 50% of adults (8) with active pulmonary TB. In these cases, the decision to initiate anti-TB treatment can be difficult, especially because sensitivity estimates for the nucleic acid amplification technique (NAAT) to detect nucleic acids of M. tuberculosis from respiratory specimen are too variable and too low to be used to exclude the diagnosis of TB (9).If combined test results are negative, immunodiagnosis by peripheral blood IFN-g release assays (IGRAs) and tuberculin skin testing (TST) may be used as rule...

No abstract

Tuberculosis (TB) is an important public health problem and remains one of the most threatening curable infectious diseases, despite improvements in diagnostic and drug susceptibility tests. The effective control of TB is based on the immediate detection of Mycobacterium tuberculosis, followed by the prompt implementation of adequate antituberculous therapy (29).The emergence of strains resistant to the major anti-TB drugs speeds up the need for rapid methods for the identification of resistant M. tuberculosis strains in order to treat the disease effectively and, at the same time, prevent the spread of resistant strains (6,8,9,16). Multidrug-resistant (MDR) M. tuberculosis strains, which are resistant at least to rifampin (RIF) and isoniazid (INH), have emerged worldwide and seriously threaten TB control and prevention programs (30).The main mutations that confer RIF resistance are located in the rpoB gene, specifically, in the well-defined 81-bp core region (22,24). About 95% of RIF-resistant strains have a mutation in this region, which facilitates the rapid development of approaches for the detection of resistance to this drug (23,24,26). However, the molecular basis of resistance to

High PCT and CRP values show a significant correlation with the bacterial etiology of lower respiratory tract infection. PCT and CRP show good sensitivity for distinguishing pneumococcal from other etiologies. PCT shows higher specificity than CRP. PCT and CRP can help make decisions about antibiotic therapy in children with lower respiratory tract infections.

We evaluated the T-SPOT.TB and Quantiferon-TB Gold In tube (QFN-G-IT) tests for diagnosing Mycobacterium tuberculosis infection. T-SPOT.TB was more sensitive than QFN-G-IT in diagnosing both active and latent infection. Both gamma interferon tests were unaffected by prior Mycobacterium bovis BCG vaccination. Among children who were not BCG vaccinated but had a positive tuberculin skin test, QFN-G-IT was negative in 53.3% of cases, and T-SPOT.TB was negative in 50% of cases.

We evaluated an immunochromatographic assay detecting pneumococcal antigen in urine samples from children diagnosed with pneumococcal pneumonia. The sensitivity and specificity of the immunochromatographic test with nonconcentrated urine (NCU) were 86.7 and 62.9%, respectively; with concentrated urine (CU), they were 100 and 11.7%, respectively. Pneumococcal antigen was also detected in 42.5% of NCU and 87.1% of CU samples from nasopharyngeal carriers. This is a nonspecific test for the diagnosis of pneumococcal pneumonia in children, particularly the very young.Streptococcus pneumoniae is presumed to be the main bacterial cause of community-acquired lower respiratory infections among children (2, 9, 12). The severity of pneumococcal diseases heightens the importance of the identification of children with pneumococcal infections (10). Detection of S. pneumoniae antigen in urine samples is an alternative for the diagnosis of pneumococcal pneumonia. We assessed the utility of a rapid immunochromatographic membrane test (ICT) (Binax Now S. pneumoniae urinary antigen test; Binax, Portland, Maine) for detecting C-polysaccharide (PnC) S. pneumoniae antigen in urine samples from children diagnosed with pneumococcal pneumonia. We also studied whether the status of pneumococcal nasopharyngeal carriage could interfere with the performance of the ICT.(Part of this study was presented at the 12th European