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New tuberculosis (TB) diagnostics are at a crossroads: their development, evaluation, and implementation is severely damaged by resource diversion due to COVID-19. Yet several technologies, especially those with potential for non-invasive non-sputum-based testing, hold promise for efficiently triaging and rapidly confirming TB near point-of-care. Such tests are, however, progressing through the pipeline slowly and will take years to reach patients and health workers. Compellingly, such tests will create new opportunities for difficult-to-diagnose populations, including primary care attendees (all-comers in high burden settings irrespective of reason for presentation) and community members (with early stage disease or risk factors like HIV), many of whom cannot easily produce sputum. Critically, all upcoming technologies have limitations that implementers and health workers need to be cognizant of to ensure optimal deployment without undermining confidence in a technology that still offers improvements over the status quo. In this state-of-the-art review, we critically appraise such technologies for active pulmonary TB diagnosis. We highlight strengths, limitations, outstanding research questions, and how current and future tests could be used in the presence of these limitations and uncertainties. Among triage tests, CRP (for which commercial near point-of-care devices exist) and computer-aided detection software with digital chest X-ray hold promise, together with late-stage blood-based assays that detect host and/or microbial biomarkers; however, aside from a handful of prototypes, the latter category has a shortage of promising late-stage alternatives. Furthermore, positive results from new triage tests may have utility in people without TB; however, their utility for informing diagnostic pathways for other diseases is under-researched (most sick people tested for TB do not have TB). For confirmatory tests, few true point-of-care options will be available soon; however, combining novel approaches like tongue swabs with established tests like Ultra have short-term promise but first require optimizations to specimen collection and processing procedures. Concerningly, no technologies yet have compelling evidence of meeting the World Health Organization optimal target product profile performance criteria, especially for important operational criteria crucial for field deployment. This is alarming as the target product profile criteria are themselves almost a decade old and require urgent revision, especially to cater for technologies made prominent by the COVID-19 diagnostic response (e.g., at-home testing and connectivity solutions). Throughout the review, we underscore the importance of how target populations and settings affect test performance and how the criteria by which these tests should be judged vary by use case, including in active case finding. Lastly, we advocate for health workers and researchers to themselves be vocal proponents of the uptake of both new tests and those – already available tests that remain suboptimally utilized. [ABSTRACT FROM AUTHOR]

An editorial is presented on the current coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It mentions that it highlighted the vulnerability of humans to infectious agents and the massive health and economic impact contagious diseases can have on life on planet earth; and also put the global disease burden from tuberculosis into greater perspective.

In high-burden settings, the diagnosis of pleural tuberculosis (TB) is frequently inferred in patients who present with lymphocyte predominant exudative effusions and high adenosine deaminase (ADA) levels. Two recent small retrospective studies suggested that the lactate dehydrogenase (LDH)/ADA ratio is significantly lower in TB than in non-TB pleural effusions and that the LDH/ADA ratio may be useful in differentiating pleural TB from other pleural exudates. We compared the pleural LDH/ADA ratios, ADA levels, and lymphocyte predominance of a prospectively collected cohort of patients with proven pleural TB (n = 160) to those with a definitive alternative diagnosis (n = 68). The mean pleural fluid LDH/ADA ratio was lower in patients with pleural TB than alternative diagnoses (6.2 vs. 34.3, p < 0.001). The area under the receiver operating characteristic curve was 0.92 (p < 0.001) for LDH/ADA ratio and 0.88 (p < 0.001) for an ADA ≥40 U/L alone. A ratio of ≤12.5 had the best overall diagnostic efficiency, while a ratio of ≤10 had a specificity of 90% and a positive predictive value of 95%, with a sensitivity of 78%, making it a clinically useful "rule in" value for pleural TB in high incidence settings. When comparing the LDH/ADA ratio to an ADA level ≥40 U/L in the presence of a lymphocyte predominant effusion, the latter performed better. When lymphocyte values are unavailable, our data suggest that the LDH/ADA ratio is valuable in distinguishing TB effusions from other pleural exudates. [ABSTRACT FROM AUTHOR]

Treatment options for intractable life-threatening haemoptysis in mechanically ventilated patients with structural lung disease who do not respond to bronchial artery embolisation (BAE) and who are deemed unfit for surgery are limited. A 26-year-old HIV-positive male with a poorly preserved CD4 count and active pulmonary tuberculosis was intubated and mechanically ventilated for persistent life-threatening haemoptysis. Two attempts at BAE failed, and life-threatening haemoptysis recurred daily for 14 days despite antituberculous therapy. He was deemed unfit for surgery during that period. We proceeded to identify the source of bleeding endoscopically and implanted an endobronchial valve in the left upper lobe bronchus. Following the collapse of the affected lobe, haemoptysis ceased and the patient was promptly liberated from mechanical ventilation. He remained haemoptysis free for the duration of his hospitalisation. Endobronchial valves, therefore, may be a viable option in patients mechanically ventilated with persistent lifethreatening haemoptysis in whom all other conventional measures fail and who are considered unfit for surgery. [ABSTRACT FROM AUTHOR]

Background: Ultrasound (US)-assisted transthoracic biopsy offers a less invasive alternative to surgical biopsy in the setting of mediastinal masses. Objectives: The aim of this 1-year prospective study was to assess the diagnostic yield and safety of a novel single-session sequential approach of US-assisted transthoracic fine-needle aspirations (TTFNA) with rapid on-site evaluation (ROSE) followed by cutting needle biopsies (CNB) performed by physicians on patients with anterosuperior mediastinal masses. Methods: US-assisted TTFNA with ROSE was performed on 45 consecutive patients (49.5 ± 27.7 years, 24 males), immediately followed by CNB where a provisional diagnosis of epithelial carcinoma or tuberculosis could not be established, provided a safety range could be assured. Results: TTFNA alone was deemed adequate by means of ROSE in 27 (60%) patients. CNB could be performed in 17 of the remaining 18. The on-site diagnosis corresponded to the final diagnosis in 26/45 (57.8%). An accurate cytological diagnosis was made in 33 (73.3%), and was more likely to be diagnostic in epithelial carcinoma and tuberculosis (28/30) than all other pathologies (5/15, p < 0.001). CNB yielded a diagnosis in 15/17 (88.2%). Overall, 42/45 patients were diagnosed by the single-session approach (93.3%). The final diagnoses included 41 neoplasms, with small cell lung cancer (n = 13) the commonest diagnosis. We observed no pneumothorax or major haemorrhage. Conclusions: A single-session sequential approach of US-assisted TTFNA with ROSE followed by CNB, where indicated, has a high diagnostic yield for anterosuperior mediastinal masses, is safe and offers an alternative to surgical biopsy. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]