Background Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain. Methods A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional. Conclusions These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.

/pdf/official-american-thoracic-society-infectious-diseases-9oaps1nu25.pdf

Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children

Pleural effusions are a common medical problem with more than 50 recognised causes including disease local to the pleura or underlying lung, systemic conditions, organ dysfunction and drugs1

Pleural effusions occur as a result of increased fluid formation and/or reduced fluid resorption The precise pathophysiology of fluid accumulation varies according to underlying aetiologies As the differential diagnosis for a unilateral pleural effusion is wide, a systematic approach to investigation is necessary The aim is to establish a diagnosis swiftly while minimising unnecessary invasive investigations and facilitating treatment, avoiding the need for repeated therapeutic aspirations when possible

Since the 2003 guideline, several clinically relevant studies have been published, allowing new recommendations regarding image guidance of pleural procedures with clear benefits to patient comfort and safety, optimum pleural fluid sampling and processing and the particular value of thoracoscopic pleural biopsies This guideline also includes a review of recent evidence for the use of new biomarkers including N-terminal pro-brain natriuretic peptide (NT-proBNP), mesothelin and surrogate markers of tuberculous pleuritis

The history and physical examination of a patient with a pleural effusion may guide the clinician as to whether the effusion is a transudate or an exudate This critical distinction narrows the differential diagnosis and directs further investigation

Clinical assessment alone is often capable of identifying transudative effusions Therefore, in an appropriate clinical setting such as left ventricular failure with a confirmatory chest x-ray, such effusions do not need to be sampled unless there are atypical features or they fail to respond to treatment

Approximately 75% of patients with pulmonary embolism and …

https://thorax.bmj.com/content/thoraxjnl/65/Suppl_2/ii4.full.pdf

Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010

Objectives To evaluate the effectiveness of available rapid diagnostic tests to identify tuberculosis (TB) infection. Data sources Electronic databases were searched from 1975 to August 2003 for tests for active TB and to March 2004 for tests for latent tuberculosis infection (LTBI). Review methods Studies were selected and evaluated that (1) tested for LTBI, (2) compared tuberculin skin test (TST) and interferon-gamma assays based on ESAT-6 and CFP-10 antigens and (3) provided information on TB exposure or bacille Calmette-Guerin (BCG) vaccination or HIV status. For each test comparison, the sensitivity, specificity and 95% confidence intervals (CIs) were calculated. Sources of heterogeneity were investigated by adding covariates to the standard regression model. The authors examined whether interferon-gamma assays were more strongly associated with high versus low TB exposure than TST. Odds ratios (ORs) were calculated for the association between test results and exposures from each study along with their 95% CIs. Within each study, the OR value for one test was divided by that for another to produce a ratio of OR (ROR). Results A total of 212 studies were included, providing 368 data sets. A further 19 studies assessing fully automated liquid culture were included. Overall, nucleic acid amplification test (NAAT) accuracy was far superior when applied to respiratory samples as opposed to other body fluids. The better quality in-house studies, were, for pulmonary TB, much better at ruling out TB than the commercial tests (higher sensitivity), but were less good at ruling it in (lower specificity), but it is not possible to recommend any one over another owing to a lack of direct test comparisons. The specificity of NAAT tests was high when applied to body fluids, for example for TB meningitis and pleural TB, but sensitivity was poor, indicating that these tests cannot be used reliably to rule out TB. High specificity estimates suggest that NAAT tests should be the first-line test for ruling in TB meningitis, but that they need to be combined with the result of other tests in order to rule out disease. Evidence for NAAT tests in other forms of TB and for phage-based tests is significantly less prolific than for those above and further research is needed to establish accuracy. There is no evidence to support the use of adenosine deaminase (ADA) tests for diagnosis of pulmonary TB; however, there is considerable evidence to support their use for diagnosis of pleural TB and to a slightly lesser extent for TB meningitis. Anti-TB antibody test performance was universally poor, regardless of type of TB. Fully automated liquid culture methods were superior to culture on solid media, in terms of their speed and their precision. In total, 13 studies were included. Assays based on RD1 specific antigens, ESAT-6 or CFP-10, correlate better with intensity of exposure, and therefore are more likely than TST/purified protein derivative (PPD)-based assays to detect LTBI accurately. An additional advantage is that they are more likely to be independent of BCG vaccination status and HIV status. Conclusions The NAAT tests provide a reliable way of increasing the specificity of diagnosis (ruling in disease) but sensitivity is too poor to rule out disease, especially in smear-negative (paucibacillary) disease where clinical diagnosis is equivocal and where the clinical need is greatest. For extra-pulmonary TB, clinical judgement has both poor sensitivity and specificity. For pleural TB and TB meningitis, adenosine deaminase tests have high sensitivity but limited specificity. NAATs have high specificity and could be used alongside ADA (or interferon-gamma) to increase sensitivity for ruling out disease and NAAT for high specificity to rule it in. All studies from low-prevalence countries strongly suggest that the RD1 antigen-based assays are more accurate than TST- and PPD-based assays for diagnosis of LTBI. If their superior diagnostic capability is found to hold up in routine clinical practice, they could confer several advantages on TB control programmes. Further research for active TB needs to establish diagnostic accuracy in a wide spectrum of patients, against an appropriate reference test, and avoiding the major sources of bias. For LTBI, research needs to address different epidemiological and clinical settings, to evaluate the performance of the main existing commercial assays in head-to-head comparison in both developed and developing countries, and to assess the role of adding more TB-specific antigens to try to improve diagnostic sensitivity.

A systematic review of rapid diagnostic tests for the detection of tuberculosis infection.

https://journal.chestnet.org/article/S0012-3692(15)38909-1/pdf

Diagnosis and Treatment of Tuberculous Pleural Effusion in 2006

Extrapulmonary tuberculosis (EPTB) constitutes about 20% of all cases of tuberculosis (TB) in Korea. Diagnosing EPTB remains challenging because clinical samples obtained from relatively inaccessible sites may be paucibacillary, thus decreasing the sensitivity of diagnostic tests. Whenever practical, every effort should be made to obtain appropriate specimens for both mycobacteriologic and histopathologic examinations. The measurement of biochemical markers in TB-affected serosal fluids (adenosine deaminase or gamma interferon) and molecular biology techniques such as polymerase chain reaction may be useful adjuncts in the diagnosis of EPTB. Although the disease usually responds to standard anti-TB drug therapy, the ideal regimen and duration of treatment have not yet been established. A paradoxical response frequently occurs during anti-TB therapy. It should be distinguished from other causes of clinical deterioration. Surgery is required mainly to obtain valid diagnostic specimens and to manage complications. Because smear microscopy or culture is not available to monitor patients with EPTB, clinical monitoring is the usual way to assess the response to treatment.

https://synapse.koreamed.org/upload/SynapseData/PDFData/0003trd/trd-78-47.pdf

Diagnosis and Treatment of Extrapulmonary Tuberculosis

OBJECTIF : Vu que les taux d'isolement de Mycobacterium tuberculosis dans les epanchements tuberculeux sont plutot faibles, un certain nombre de marqueurs biochimiques et biologiques ont ete proposes pour le diagnostic de la pleuresie tuberculeuse, notamment l'adenosine deaminase (ADA) et l'interferon-γ (IFN-γ). Nous faisons un resume de la litterature sur la valeur de ADA et IFN-γ comme facteurs predictifs d'une pleuresie tuberculeuse. METHODES: Apres une revue systematique des etudes en langue anglaise, nous avons utilise l'analyse « summary receiver operating characteristic curve » (SROC) pour determiner la precision diagnostique cumulative des deux marqueurs et le theoreme de Bayes pour calculer la probabilite de maladie apres le test dans le contexte de differentes prevalences de pleuresie tuberculeuse. Nous avons etudie et fait etat de la qualite des etudes primaires. RESULTATS: Entre 1978 et novembre 2000, 31 etudes contenaient des donnees suffisantes pour la determination a la fois de la sensibilite et de la specificite pour ADA (impliquant 4.738 patients) et 13 pour IFN-γ (incluant 1.189 patients). La courbe SROC a fourni une sensibilite et une specificite conjointes maximales de 93% pour ADA et de 96% pour IFN-γ. Dans le contexte d'une prevalence des epanchements tuberculeux de 5%, 25% et 85%, la probabilite post-test pour un test ADA negatif a ete de 0,4%, 2,4% et 24% et pour un test IFN-γ negatif de 0,22%, 1,2% et 17%. CONCLUSION: Avec la precaution que les limitations dans la conception des etudes resumees ici pourraient avoir fausse les estimations de performance des tests, ADA et IFN-γ semblent etre raisonnablement precis pour la detection de la pleuresie tuberculeuse.

Adenosine deaminase and interferon gamma measurements for the diagnosis of tuberculous pleurisy: a meta-analysis.

Abstract Background Remdesivir is widely used for treatment of SARS-CoV-2 pneumonia. The aim of this study was to evaluate the characteristics of patients with moderate-to-severe COVID-19 treated with remdesivir, and their outcomes during hospitalization. Methods This retrospective observational multicenter study included consecutive patients, hospitalized for moderate-to-severe COVID-19 (September 2020—September 2021), who were treated with remdesivir. Results One thousand four patients were enrolled, all with onset of symptoms occurring less than 10 days before starting remdesivir; 17% of patients had 4 or more concomitant diseases. Remdesivir was well tolerated, adverse drug reactions (ADRs) being reported in 2.3% of patients. In-hospital death occurred in 80 patients (8.0%). The median timing of the first remdesivir dose was 5 days after symptom onset. The following endpoints did not differ according to the time span from the onset of symptoms to the first dose: length of hospitalization, in-hospital death, composite outcome (in-hospital death and/or endotracheal intubation). Advanced age, number of comorbidities ≥ 4, and severity of respiratory failure at admission were associated with poor in-hospital outcomes. Conclusion In a real-world setting, remdesivir proved to be a safe and well-tolerated treatment for moderate-to-severe COVID-19. In patients receiving remdesivir less than 3 or 5 days from the onset of SARS-CoV-2 symptoms, mortality and the need for mechanical ventilation did not differ from the rest of the sample. 

https://bmcinfectdis.biomedcentral.com/counter/pdf/10.1186/s12879-023-08422-6

Real-world use of remdesivir for the treatment of patients admitted to Italian hospitals with COVID-19: the nationwide retrospective FADOI-RECOVER study

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Adenosine deaminase and interferon gamma measurements for the diagnosis of tuberculous pleurisy: a meta-analysis.

Real-world use of remdesivir for the treatment of patients admitted to Italian hospitals with COVID-19: the nationwide retrospective FADOI-RECOVER study