Poor concordance between interferon-γ release assays and tuberculin skin tests in diagnosis of latent tuberculosis infection among HIV-infected individuals

<p>Abstract</p> <p>Background</p> <p>A new generation of diagnostic tests, the interferon-γ release assays (IGRAs), have been developed for the detection of latent tuberculosis infection (LTBI). Limited data are available on their use in HIV-infected persons.</p> <p>Methods</p> <p>A cross-sectional study was carried out at 2 HIV clinics in Atlanta to assess the utility of two IGRA tests (T-SPOT.TB [TSPOT] and QuantiFERON-TB Gold in Tube [QFT-3G]) compared to the tuberculin skin test (TST).</p> <p>Results</p> <p>336 HIV-infected persons were enrolled. Median CD4 count was 335 cells/μl and median HIV viral load was 400 copies/ml. Overall, 27 patients (8.0%) had at least 1 positive diagnostic test for LTBI: 7 (2.1%) had a positive TST; 9 (2.7%) a positive QFT-3G; and 14 (4.2%) a positive TSPOT. Agreement between the 3 diagnostic tests was poor: TST and TSPOT, [κ = 0.16, 95% CI (-0.06, 0.39)], TST and QFT-3G [κ = 0.23, 95% CI (-0.05, 0.51)], QFT-3G and TSPOT [κ = 0.06, 95% CI (-0.1, 0.2)]. An indeterminate test result occurred among 6 (1.8%) of QFT-3G and 47 (14%) of TSPOT tests. In multivariate analysis, patients with a CD4 ≤ 200 cells/μl were significantly more likely to have an indeterminate result [OR = 3.6, 95% CI (1.9, 6.8)].</p> <p>Conclusion</p> <p>We found a low prevalence of LTBI and poor concordance between all 3 diagnostic tests. Indeterminate test results were more likely at CD4 counts ≤ 200 cells/μl. Additional studies among HIV-infected populations with a high prevalence of TB are needed to further assess the utility of IGRAs in this patient population.</p

Evaluation of immune responses in HIV infected patients with pleural tuberculosis by the QuantiFERON® TB-Gold interferon-gamma assay

<p>Abstract</p> <p>Background</p> <p>Diagnosis of tuberculous (TB) pleuritis is difficult and better diagnostic tools are needed. New blood based interferon-gamma (IFN-γ) tests are promising, but sensitivity could be low in HIV positive patients. The IFN-γ tests have not yet been validated for use in pleural fluid, a compartment with higher level of immune activation than in blood.</p> <p>Methods</p> <p>The QuantiFERON TB^®-Gold (QFT-TB) test was analysed in blood and pleural fluid from 34 patients presenting with clinically suspected pleural TB. Clinical data, HIV status and CD4 cell counts were recorded. Adenosine deaminase activity (ADA) analysis and TB culture were performed on pleural fluid.</p> <p>Results</p> <p>The patients were categorised as 'confirmed TB' (n = 12), 'probable TB' (n = 16) and 'non-TB' pleuritis (n = 6) based on TB culture results and clinical and biochemical criteria. The majority of the TB patients were HIV infected (82%). The QFT-TB in pleural fluid was positive in 27% and 56% of the 'confirmed TB' and 'probable TB' cases, respectively, whereas the corresponding sensitivities in blood were 58% and 83%. Indeterminate results in blood (25%) were caused by low phytohemagglutinin (PHA = positive control) IFN-γ responses, significantly lower in the TB patients as compared to the 'non-TB' cases (p = 0.02). Blood PHA responses correlated with CD4 cell count (r = 0.600, p = 0.028). In contrast, in pleural fluid indeterminate results (52%) were caused by high Nil (negative control) IFN-γ responses in both TB groups. Still, the Nil IFN-γ responses were lower than the TB antigen responses (p < 0.01), offering a conclusive test for half of the patients. We did not find any correlation between blood CD4 cell count and IFN-γ responses in pleural fluid.</p> <p>Conclusion</p> <p>The QFT-TB test in blood could contribute to the diagnosis of TB pleuritis in the HIV positive population. Still, the number of inconclusive results is too high to recommend the commercial QFT-TB test for routine use in pleural fluid in a TB/HIV endemic resource-limited setting.</p

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

Knowledge-guided docking: accurate prospective prediction of bound configurations of novel ligands using Surflex-Dock

Prediction of the bound configuration of small-molecule ligands that differ substantially from the cognate ligand of a protein co-crystal structure is much more challenging than re-docking the cognate ligand. Success rates for cross-docking in the range of 20–30 % are common. We present an approach that uses structural information known prior to a particular cutoff-date to make predictions on ligands whose bounds structures were determined later. The knowledge-guided docking protocol was tested on a set of ten protein targets using a total of 949 ligands. The benchmark data set, called PINC (“PINC Is Not Cognate”), is publicly available. Protein pocket similarity was used to choose representative structures for ensemble-docking. The docking protocol made use of known ligand poses prior to the cutoff-date, both to help guide the configurational search and to adjust the rank of predicted poses. Overall, the top-scoring pose family was correct over 60 % of the time, with the top-two pose families approaching a 75 % success rate. Correct poses among all those predicted were identified nearly 90 % of the time. The largest improvements came from the use of molecular similarity to improve ligand pose rankings and the strategy for identifying representative protein structures. With the exception of a single outlier target, the knowledge-guided docking protocol produced results matching the quality of cognate-ligand re-docking, but it did so on a very challenging temporally-segregated cross-docking benchmark

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease