More about the Deformation of Our Language

<div><p>Background</p><p>Although tuberculosis is transmitted by the airborne route, direct information on the natural output of bacilli into air by source cases is very limited. We sought to address this through sampling of expelled aerosols in face masks that were subsequently analyzed for mycobacterial contamination.</p><p>Methods</p><p>In series 1, 17 smear microscopy positive patients wore standard surgical face masks once or twice for periods between 10 minutes and 5 hours; mycobacterial contamination was detected using a bacteriophage assay. In series 2, 19 patients with suspected tuberculosis were studied in Leicester UK and 10 patients with at least one positive smear were studied in The Gambia. These subjects wore one FFP30 mask modified to contain a gelatin filter for one hour; this was subsequently analyzed by the Xpert MTB/RIF system.</p><p>Results</p><p>In series 1, the bacteriophage assay detected live mycobacteria in 11/17 patients with wearing times between 10 and 120 minutes. Variation was seen in mask positivity and the level of contamination detected in multiple samples from the same patient. Two patients had non-tuberculous mycobacterial infections. In series 2, 13/20 patients with pulmonary tuberculosis produced positive masks and 0/9 patients with extrapulmonary or non-tuberculous diagnoses were mask positive. Overall, 65% of patients with confirmed pulmonary mycobacterial infection gave positive masks and this included 3/6 patients who received diagnostic bronchoalveolar lavages.</p><p>Conclusion</p><p>Mask sampling provides a simple means of assessing mycobacterial output in non-sputum expectorant. The approach shows potential for application to the study of airborne transmission and to diagnosis.</p></div

High levels of neurological involvement but low mortality in miliary tuberculosis: a six-year case-series from the United Kingdom

Tuberculosis (TB) remains one of the biggest global health challenges. Whilst the greatest burden of active disease is seen in Asia and Africa [1], TB remains a significant issue in the UK. Miliary TB is one of the severest manifestations of TB disease [2–4]. Up-to-date clinicopathological data on miliary TB from the developed world are lacking. We undertook a comprehensive 6-year review (2007–2012) of cases presenting to a single UK centre with an ethnically diverse population with high levels of population exchange with the Indian Subcontinent and Africa. Miliary TB was defined as the presence of miliary nodules on thoracic imaging in patients who presented with symptoms compatible with the diagnosis and either culture of Mycobacterium tuberculosis complex or culture-negative patients with clinical and/or histological features compatible with TB who were commenced on a course of antituberculous therapy (ATT)

Additional file 1: of A nested case–control study of predictors for tuberculosis recurrence in a large UK Centre

Summary of definitions used in the study. Tables detailing: immunosuppressive medication received by patients; site of tuberculosis disease for cases and controls; MIRU VNTR strain type data for paired isolates; demographic data for reinfection and relapse cases. (DOCX 107 kb

Interferon-gamma release assay conversion after M. tuberculosis exposure specifically associates with greater risk of progression to tuberculosis: a prospective cohort study in Leicester (UK)

ObjectivesWe investigated whether quantifying the serial QuantiFERON-TB Gold (QFT) response improves tuberculosis (TB) risk stratification in pulmonary TB (PTB) contacts.Methods297 untreated adult household PTB contacts, QFT tested at baseline and 3 months after index notification, were prospectively observed (median 1460 days). Normal variance of serial QFT responses was established in 46 extra-pulmonary TB contacts. This informed categorisation of the response in QFT-positive PTB contacts as: converters; persistently QFT-positive with significant increase (PPincrease); and without significant increase (PPno-increase).ResultsEight co-prevalent TB (disease ≤ 3 months after index notification) and 12 incident TB (>3 months after index notification) cases were diagnosed. Genetic linkage to the index strain was confirmed in all culture-positive progressors. Cumulative 2-year incident TB risk in QFT-positive contacts was 8.4% (95% CI, 3.0% - 13.6%); stratifying by serial QFT response, significantly higher risk was observed in QFT-converters (28%), compared with PPno-increase (4.8%) and PPincrease (3.7%). Converters were characterised by exposure to index cases with a shorter interval from symptom onset to diagnosis (median reduction 50.0 days, p=0.013).ConclusionQFT conversion rather than quantitative changes of a persistently positive serial QFT response, associates with greater TB risk and exposure to rapidly progressive TB

A nested case-control study of predictors for tuberculosis recurrence in a large UK Centre

Background: Tuberculosis (TB) recurrence represents a challenge to control programs. In low incidence countries, the prevailing risk factors leading to recurrence are poorly characterised. Methods: We conducted a nested case-control study using the Leicester TB service TBIT database. Cases were identified from database notifications between 1994 and 2014. Controls had one episode and were matched to cases on a ratio of two to one by the date of notification. Multiple imputation was used to account for missing data. Multivariate conditional logistic regression analysis was employed to identify clinical, sociodemographic and TB specific risk factors for recurrence. Results: From a cohort of 4628 patients, 82 TB recurrences occurred (1.8%). Nineteen of 82 patients had paired isolates with MIRU-VNTR strain type profiles available, of which 84% were relapses and 16% reinfections. On multivariate analysis, smoking (OR 3.8; p = 0.04), grade 3/4 adverse drug reactions (OR 5.6; p = 0.02), ethnicity 'Indian subcontinent' (OR 8.5; p = <0.01), ethnicity 'other' (OR 31.2; p = 0.01) and receipt of immunosuppressants (OR 6.8; p = <0.01) were independent predictors of TB recurrence. CONCLUSIONS: Within this UK setting, the rate of TB recurrence was low, predominantly due to relapse. The identification of an elevated recurrence risk amongst the ethnic group contributing most cases to the national TB burden presents an opportunity to improve individual and population health

Interferon-gamma release assay conversion after M. tuberculosis exposure specifically associates with greater risk of progression to tuberculosis: a prospective cohort study in Leicester (UK)

ObjectivesWe investigated whether quantifying the serial QuantiFERON-TB Gold (QFT) response improves tuberculosis (TB) risk stratification in pulmonary TB (PTB) contacts.Methods297 untreated adult household PTB contacts, QFT tested at baseline and 3 months after index notification, were prospectively observed (median 1460 days). Normal variance of serial QFT responses was established in 46 extra-pulmonary TB contacts. This informed categorisation of the response in QFT-positive PTB contacts as: converters; persistently QFT-positive with significant increase (PPincrease); and without significant increase (PPno-increase).ResultsEight co-prevalent TB (disease ≤ 3 months after index notification) and 12 incident TB (>3 months after index notification) cases were diagnosed. Genetic linkage to the index strain was confirmed in all culture-positive progressors. Cumulative 2-year incident TB risk in QFT-positive contacts was 8.4% (95% CI, 3.0% - 13.6%); stratifying by serial QFT response, significantly higher risk was observed in QFT-converters (28%), compared with PPno-increase (4.8%) and PPincrease (3.7%). Converters were characterised by exposure to index cases with a shorter interval from symptom onset to diagnosis (median reduction 50.0 days, p=0.013).ConclusionQFT conversion rather than quantitative changes of a persistently positive serial QFT response, associates with greater TB risk and exposure to rapidly progressive TB

Comprehensive respiratory assessment in advanced COPD: a 'campus to clinic' translational framework

Comprehensive respiratory assessment in advanced COPD: a 'campus to clinic' translational framewor

A novel high sensitivity bacteriophage based assay identifies low level M.tuberculosis bacteraemia in immunocompetent patients with active and incipient TB

Haematogenous dissemination of M. tuberculosis (Mtb) is critical to pathogenesis of progressive tuberculous infection in animal models. Using a novel phage-based blood assay, we report the first concordant evidence in well-characterised immunocompetent human cohorts, demonstrating associations of Mtb bacteraemia with progressive phenotypes of latent infection and active pulmonary TB respectively

Prognostication of co-morbidity clusters on hospitalisation and mortality in advanced COPD

RationaleAs the prevalence of multimorbidity increases, understanding the impact of isolated comorbidities in people COPD becomes increasingly challenging. A simplified model of common comorbidity patterns may improve outcome prediction and allow targeted therapy.ObjectivesTo assess whether comorbidity phenotypes derived from routinely collected clinical data in people with COPD show differences in risk of hospitalisation and mortality.MethodsTwelve clinical measures related to common comorbidities were collected during annual reviews for people with advanced COPD and k-means cluster analysis performed. Cox proportional hazards with adjustment for covariates was used to determine hospitalisation and mortality risk between clusters.Measurements and main resultsIn 203 participants (age 66 ± 9 years, 60 % male, FEV1%predicted 31 ± 10 %) no comorbidity in isolation was predictive of worse admission or mortality risk. Four clusters were described: cluster A (cardiometabolic and anaemia), cluster B (malnourished and low mood), cluster C (obese, metabolic and mood disturbance) and cluster D (less comorbid). FEV1%predicted did not significantly differ between clusters. Mortality risk was higher in cluster A (HR 3.73 [95%CI 1.09-12.82] p = 0.036) and B (HR 3.91 [95%CI 1.17-13.14] p = 0.027) compared to cluster D. Time to admission was highest in cluster A (HR 2.01 [95%CI 1.11-3.63] p = 0.020). Cluster C was not associated with increased risk of mortality or hospitalisation.ConclusionsDespite presence of advanced COPD, we report striking differences in prognosis for both mortality and hospital admissions for different co-morbidity phenotypes. Objectively assessing the multi-system nature of COPD could lead to improved prognostication and targeted therapy for patients

Survival following pulmonary rehabilitation in patients with COPD: the effect of program completion and change in incremental shuttle walking test distance.

Rationale: Pulmonary rehabilitation (PR) in patients with COPD has consistently been shown to produce benefits in exercise capacity, symptoms, and health status. The data surrounding survival following PR are less clear. Our aims were to compare the long-term survival in two cohorts of patients referred for PR; those who successfully completed PR, and a comparator group constructed from patients who either did not complete PR or did not start the program. Additionally, we compared survival between those people who were able to achieve a clinically meaningful improvement in exercise capacity (incremental shuttle walking test) following PR with those who were not. Methods: A retrospective longitudinal analysis of clinical service outcomes was conducted to compare the long-term survival in "completers" and "non-completers" of rehabilitation at two hospitals within the University Hospitals of Leicester NHS Trust from January 1, 2000 to February 23, 2012. For "completers", we also analyzed survival in those meeting (and not meeting) the desired level of change in the incremental shuttle walking test (≥50 m vs 50 m change in walking distance) was also associated with improved survival