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Background: Community-acquired pneumonia (CAP) causes a large burden of disease. Due to difficulties in obtaining representative respiratory samples and insensitive standard microbiological methods, the microbiological aetiology of CAP is difficult to ascertain. With a few exceptions, standard-of-care diagnostics are too slow to influence initial decisions on antimicrobial therapy. The management of CAP is therefore largely based on empirical treatment guidelines. Empiric antimicrobial therapy is often initiated in the primary care setting, affecting diagnostic tests based on conventional bacterial culture in hospitalized patients. Implementing rapid molecular testing may improve both the proportion of positive tests and the time it takes to obtain test results. Both measures are important for initiation of pathogen-targeted antibiotics, involving rapid de-escalation or escalation of treatment, which may improve antimicrobial stewardship and potentially patient outcome.Methods: Patients presenting to the emergency department of Haukeland University Hospital (HUH) in Bergen, Norway, will be screened for inclusion into a pragmatic randomised controlled trial (RCT). Eligible patients with a suspicion of CAP will be included and randomised to receive either standard-of-care methods (standard microbiological testing) or standard-of-care methods in addition to testing by the rapid and comprehensive real-time multiplex PCR panel, the BioFire® FilmArray® Pneumonia Panel plus (FAP plus) (bioMérieux S.A., Marcy-l'Etoile, France). The results of the FAP plus will be communicated directly to the treating staff within ~2 h of sampling.Discussion: We will examine if rapid use of FAP plus panel in hospitalized patients with suspected CAP can improve both the time to and the proportion of patients receiving pathogen-directed treatment, thereby shortening the exposure to unnecessary antibiotics and the length of hospital admission, compared to the standard-of-care arm. The pragmatic design together with broad inclusion criteria and a straightforward intervention could make our results generalizable to other similar centres.Trial Registration: ClinicalTrials.gov NCT04660084 . Registered on December 9, 2020. [ABSTRACT FROM AUTHOR]

Setting: Tertiary care hospitals in India., Objective: To compare the performance of the QuantiFERON®-TB Gold In-Tube test (QFT-GIT) with that of the tuberculin skin test (TST) in the diagnosis of intrathoracic childhood tuberculosis (TB)., Methods: Children with intrathoracic TB were enrolled in a randomised controlled trial studying micronutrient supplementation in intrathoracic TB. They underwent TST and QFT-GIT before starting daily anti-tuberculosis treatment., Results: Of 362 children (median age 115.5 months, IQR 73-144, 55% girls) enrolled in the study, microbiological confirmation of TB was obtained in 128 (35%). The TST was positive in 337 (93%, 95%CI 90-95.5) and QFT-GIT in 297 (82%, 95%CI 77.8-85.6). Sensitivity of TST and QFT-GIT in culture-confirmed TB cases was respectively 90.5% (95%CI 84.1-94.5) and 82.6% (95%CI 74.9-88.4). QFT-GIT positivity rate correlated with TST induration (P < 0.001). TST was influenced by the disease spectrum (P = 0.004) and the age of the children (P = 0.002); QFT-GIT remained unaffected by these factors. Bacille Calmette-Guérin immunisation status, weight-for-age Z-scores and microbiological confirmation of Mycobacterium tuberculosis did not influence the performance of either test., Conclusion: In high-burden countries, QFT-GIT is comparable to TST and offers no added advantage in the diagnosis of childhood intrathoracic TB.

Background: Data on the association between exposure to environmental tobacco smoke (ETS) and Mycobacterium tuberculosis infection in children are limited., Objective: To examine the dose-response effect of ETS exposure on the risk of M. tuberculosis infection in children in a high tuberculosis (TB) burden setting., Methods: This cross-sectional study included healthy South African children from impoverished urban communities. Data were collected on household ETS and M. tuberculosis exposure, demographics, socio-economic and anthropometric data, M. tuberculosis infection, human immunodeficiency virus and TB disease status., Results: Among 196 children (median age 6.8 years, range 0.3-15.9), 97 (49.5%) were M. tuberculosis - i nfected (tuberculin skin test [TST] ≥ 10 mm) and 128 (65.3%) reported ETS exposure; of these, 81/128 (63.3%) were exposed to ≥ 2 household smokers. The presence of ≥ 2 household smokers was associated with M. tuberculosis infection in univariate analysis, irrespective of TST cut-off point. In analysis adjusting for M. tuberculosis exposure, socio-economic status, age and previous TB treatment, ETS exposure remained associated with M. tuberculosis infection. In univariate and multivariate analysis, pack-years of exposure were associated with risk of TB infection., Discussion: Exposure to ETS is associated with M. tuberculosis infection in children after adjustment for multiple variables, with a dose-response relationship between the degree of ETS exposure and risk of infection. Public health interventions to reduce exposure to tobacco smoke among children in high TB burden settings are urgently needed.