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

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

The impact, effectiveness and outcomes of targeted screening thresholds for programmatic latent TB infection testing in HIV: cohort study results.

Background:  Screening and treatment for latent tuberculosis infection (LTBI) are key for TB control. In the UK, the National Institute of Health and Care Excellence (NICE) and the British HIV Association (BHIVA) give conflicting guidance on which groups of people living with HIV (PLWH) should be screened, and previous national analysis demonstrated heterogeneity in how guidance is applied. There is an urgent need for a firmer clinical effectiveness evidence base on which to build screening policy. Methods:  We conducted a systematic, programmatic LTBI screening intervention for all PLWH receiving care in Leicester, UK. We compared yields (percentage IGRA positive) and number of tests required when applying the NICE and BHIVA testing strategies, as well as strategies targeting screening by TB incidence in patients’ countries of birth. Results:  Of 1053 PLWH tested, 118 were IGRA-positive (11.2%). Positivity was associated with higher TB incidence in country-of-birth (adjusted odds ratio, 50–149 cases compared to 150/100,000 or any sub-Saharan African country, would have correctly identified 89·8% of all LTBI cases while cutting tests required by 46·1% compared to NICE guidance, performing as well as BHIVA 2018 guidance. Conclusions:  Targeting screening to higher-risk PLWH increases yield and reduces the number requiring testing. Our proposed ‘PLWH-LTBI streamlined guidance’ offers a simplified approach, with the potential to improve national LTBI screening implementation.</p

Airway bacteria measured by quantitative polymerase chain reaction and culture in patients with stable COPD: relationship with neutrophilic airway inflammation, exacerbation frequency, and lung function

BACKGROUND: Potentially pathogenic microorganisms can be detected by quantitative real-time polymerase chain reaction (qPCR) in sputum from patients with COPD, although how this technique relates to culture and clinical measures of disease is unclear. We used cross-sectional and longitudinal data to test the hypotheses that qPCR is a more sensitive measure of bacterial presence and is associated with neutrophilic airway inflammation and adverse clinical outcomes. METHODS: Sputum was collected from 174 stable COPD subjects longitudinally over 12 months. Microbial sampling using culture and qPCR was performed. Spirometry and sputum measures of airway inflammation were assessed. FINDINGS: Sputum was qPCR-positive (>10(6) copies/mL) in 77/152 samples (Haemophilus influenzae [n=52], Moraxella catarrhalis [n=24], Streptococcus pneumoniae [n=19], and Staphylococcus aureus [n=7]). Sputum was culture-positive in 50/174 samples, with 49 out of 50 culture-positive samples having pathogen-specific qPCR bacterial loads >10(6) copies/mL. Samples that had qPCR copy numbers >10(6)/mL, whether culture-positive or not, had increased sputum neutrophil counts. H. influenzae qPCR copy numbers correlated with sputum neutrophil counts (r=0.37, P10(6)/mL three or more times in 19 patients, eight of whom were repeatedly sputum culture-positive. Persistence, whether defined by culture, qPCR, or both, was associated with a higher sputum neutrophil count, lower forced expiratory volume in 1 second (FEV1), and worsened quality of life. INTERPRETATION: qPCR identifies a significant number of patients with potentially bacteria-associated neutrophilic airway inflammation and disease that are not identified by traditional culture-based methods

Schematic of mask processing for phage assay.

<p>See text for abbreviations.</p

<b>GeneXpert ASSAY APPLIED TO FILTER INSERTS.</b>

<p>BAL =  bronchoalveolar lavage; LN =  lymph node aspirate, PA =  pleural aspirate, Sp =  sputum, SC =  scanty, ND =  Not done.</p>‡<p>UK Smear result from local diagnostic service, Gambia smear result from MRC lab. All Gambian patients had a prior smear-positive from their local health clinic.</p><p>*All patients diagnosed with extrapulmonary TB were sputum smear- and culture-negative.</p>†<p>Mask collected day 5 of TB treatment.</p

FFP30 mask with filter adapted for sampling.

<p>FFP30 mask with filter adapted for sampling.</p

<b>SERIES 1, PHAGE ASSAYS ON SURGICAL MASKS.</b>

<p>ND =  not done; U =  not recorded.</p><p>*<i>M. kansasii</i> isolated.</p>†<p><i>M. avium</i>isolated.</p>‡<p>Patients 1–9 - RB assay; 10–17 – OM assay.</p>¶<p>Pre-chemotherapy samples.</p