New tools for detecting latent tuberculosis infection: evaluation of RD1-specific long-term response

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma (IFN-γ) release assays (IGRAs) were designed to detect latent tuberculosis infection (LTBI). However, discrepancies were found between the tuberculin skin test (TST) and IGRAs results that cannot be attributed to prior Bacille Calmètte Guerin vaccinations. The aim of this study was to evaluate tools for improving LTBI diagnosis by analyzing the IFN-γ response to RD1 proteins in prolonged (long-term response) whole blood tests in those subjects resulting negative to assays such as QuantiFERON-TB Gold In tube (QFT-IT).</p> <p>Methods</p> <p>The study population included 106 healthy TST⁺individuals with suspected LTBI (recent contact of smear-positive TB and homeless) consecutively enrolled. As controls, 13 healthy subjects unexposed to <it>M. tuberculosis </it>(TST^-, QFT-IT^-) and 29 subjects with cured pulmonary TB were enrolled. IFN-γ whole blood response to RD1 proteins and QFT-IT were evaluated at day 1 post-culture. A prolonged test evaluating long-term IFN-γ response (7-day) to RD1 proteins in diluted whole blood was performed.</p> <p>Results</p> <p>Among the enrolled TST⁺subjects with suspected LTBI, 70/106 (66.0%) responded to QFT-IT and 64/106 (60.3%) to RD1 proteins at day 1. To evaluate whether a prolonged test could improve the detection of LTBI, we set up the test using cured TB patients (with a microbiologically diagnosed past pulmonary disease) who resulted QFT-IT-negative and healthy controls as comparator groups. Using this assay, a statistically significant difference was found between IFN-γ levels in cured TB patients compared to healthy controls (p < 0.006). Based on these data, we constructed a receiver operating characteristic (ROC) curve and we calculated a cut-off. Based on the cut-off value, we found that among the 36 enrolled TST+ subjects with suspected LTBI not responding to QFT-IT, a long term response to RD1 proteins was detected in 11 subjects (30.6%).</p> <p>Conclusion</p> <p>These results indicate that IFN-γ long-term response to <it>M. tuberculosis </it>RD1 antigens may be used to detect past infection with <it>M. tuberculosis </it>and may help to identify additional individuals with LTBI who resulted negative in the short-term tests. These data may provide useful information for improving immunodiagnostic tests for tuberculosis infection, especially in individuals at high risk for active TB.</p

Within-host evolution of Staphylococcus aureus during asymptomatic carriage

Background Staphylococcus aureus is a major cause of healthcare associated mortality, but like many important bacterial pathogens, it is a common constituent of the normal human body flora. Around a third of healthy adults are carriers. Recent evidence suggests that evolution of S. aureus during nasal carriage may be associated with progression to invasive disease. However, a more detailed understanding of within-host evolution under natural conditions is required to appreciate the evolutionary and mechanistic reasons why commensal bacteria such as S. aureus cause disease. Therefore we examined in detail the evolutionary dynamics of normal, asymptomatic carriage. Sequencing a total of 131 genomes across 13 singly colonized hosts using the Illumina platform, we investigated diversity, selection, population dynamics and transmission during the short-term evolution of S. aureus. Principal Findings We characterized the processes by which the raw material for evolution is generated: micro-mutation (point mutation and small insertions/deletions), macro-mutation (large insertions/deletions) and the loss or acquisition of mobile elements (plasmids and bacteriophages). Through an analysis of synonymous, non-synonymous and intergenic mutations we discovered a fitness landscape dominated by purifying selection, with rare examples of adaptive change in genes encoding surface-anchored proteins and an enterotoxin. We found evidence for dramatic, hundred-fold fluctuations in the size of the within-host population over time, which we related to the cycle of colonization and clearance. Using a newly-developed population genetics approach to detect recent transmission among hosts, we revealed evidence for recent transmission between some of our subjects, including a husband and wife both carrying populations of methicillin-resistant S. aureus (MRSA). Significance This investigation begins to paint a picture of the within-host evolution of an important bacterial pathogen during its prevailing natural state, asymptomatic carriage. These results also have wider significance as a benchmark for future systematic studies of evolution during invasive S. aureus disease

Implementation of the evidence for the improvement of nursing care to the critical patient's family: a participatory action research

Background: There are many descriptive studies regarding the needs of the family, as well as those regarding nursing care aimed directly at family members. However, there is no widespread application of such evidence in clinical practice. There has also been no analysis made of the evolution of patterns of knowing during the act of improving clinical practice. Therefore, the purpose of the study is to understand the change process aimed at improving care to critical patient's families, and to explore the evolution of patterns of knowing that nurses use in this process. Methods: Qualitative study with a Participatory Action Research method, in accordance with the Kemmis and McTaggart model. In this model, nurses can observe their practice, reflect upon it and compare it with scientific evidence, as well as define, deploy and evaluate improvement strategies adapted to the context. Simultaneously, the process of empowerment derived from the Participatory Action Research allows for the identification of patterns of knowing and their development over time. The research will take place in the Intensive Care Units of a tertiary hospital. The participants will be nurses who are part of the regular workforce of these units, with more than five years of experience in critical patients, and who are motivated to consider and critique their practice. Data collection will take place through participant observation, multi-level discussion group meetings and documentary analysis. A content analysis will be carried out, following a process of codification and categorisation, with the help of Nvivo10. The approval date and the beginning of the funding were December 2012 and 2013, respectively. Discussion: The definition, introduction and evaluation of care strategies for family members will allow for their real and immediate implementation in practice. The study of the patterns of knowing in the Participatory Action Research will be part of the theoretical and practical feedback process of a professional discipline. Also, the identification of the construction and evolution of knowledge will provide decision elements to managers and academics when choosing strategies for increased quality

Visual journeys through wordless narratives: An international inquiry with immigrant children and the arrival.

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