-
Respirology (Carlton, Vic.) Oct 2019Tuberculous effusion is a common disease entity with a spectrum of presentations from a largely benign effusion, which resolves completely, to a complicated effusion... (Review)
Review
Tuberculous effusion is a common disease entity with a spectrum of presentations from a largely benign effusion, which resolves completely, to a complicated effusion with loculations, pleural thickening and even frank empyema, all of which may have a lasting effect on lung function. The pathogenesis is a combination of true pleural infection and an effusive hypersensitivity reaction, compartmentalized within the pleural space. Diagnostic thoracentesis with thorough pleural fluid analysis including biomarkers such as adenosine deaminase and gamma interferon achieves high accuracy in the correct clinical context. Definitive diagnosis may require invasive procedures to demonstrate histological evidence of caseating granulomas or microbiological evidence of the organism on smear or culture. Drug resistance is an emerging problem that requires vigilance and extra effort to acquire a complete drug sensitivity profile for each tuberculous effusion treated. Nucleic acid amplification tests such as Xpert MTB/RIF can be invaluable in this instance; however, the yield is low in pleural fluid. Treatment consists of standard anti-tuberculous therapy or a guideline-based individualized regimen in the case of drug resistance. There is low-quality evidence that suggests possible benefit from corticosteroids; however, they are not currently recommended due to concomitant increased risk of adverse effects. Small studies report some short- and long-term benefit from interventions such as therapeutic thoracentesis, intrapleural fibrinolytics and surgery but many questions remain to be answered.
Topics: Adenosine Deaminase; Antitubercular Agents; Body Fluids; Drug Resistance, Bacterial; Humans; Interferon-gamma; Pleural Effusion; Thoracentesis; Tuberculosis, Pleural
PubMed: 31418985
DOI: 10.1111/resp.13673 -
Frontiers in Cellular and Infection... 2020is primarily a respiratory pathogen. However, 15% of infections worldwide occur at extrapulmonary sites causing additional complications for diagnosis and treatment of... (Review)
Review
is primarily a respiratory pathogen. However, 15% of infections worldwide occur at extrapulmonary sites causing additional complications for diagnosis and treatment of the disease. In addition, dissemination of out of the lungs is thought to be more than just a rare event leading to extrapulmonary tuberculosis, but rather a prerequisite step that occurs during all infections, producing secondary lesions that can become latent or productive. In this review we will cover the clinical range of extrapulmonary infections and the process of dissemination including evidence from both historical medical literature and animal experiments for dissemination and subsequent reseeding of the lungs through the lymphatic and circulatory systems. While the mechanisms of dissemination are not fully understood, we will discuss the various models that have been proposed to address how this process may occur and summarize the bacterial virulence factors that facilitate dissemination.
Topics: Animals; Dendritic Cells; Disease Models, Animal; Epithelial Cells; Humans; Lung; Macrophages, Alveolar; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Pleural; Virulence Factors
PubMed: 32161724
DOI: 10.3389/fcimb.2020.00065 -
Proceedings (Baylor University. Medical... Oct 2019A 35-year-old woman with previously untreated latent tuberculosis was admitted to the hospital for management of a right-sided empyema. After a prolonged hospitalization...
A 35-year-old woman with previously untreated latent tuberculosis was admitted to the hospital for management of a right-sided empyema. After a prolonged hospitalization and several interventions, including chest tubes, bronchoscopy with bronchoalveolar lavage, and a video-assisted thoracoscopic surgery, positive acid-fast bacilli cultures on the initial thoracentesis ultimately led to the diagnosis of pleural tuberculosis. This case highlights the importance of utilizing a combination of diagnostic tests to diagnose pleural tuberculosis, especially in the setting of a negative pleural adenosine deaminase level.
PubMed: 31656443
DOI: 10.1080/08998280.2019.1646599 -
Clinical Case Reports Mar 2022An 83-year-old man was diagnosed with tuberculous pleuroperitonitis on a thoracoscopic pleural biopsy. It may be due to endogenous reactivation of the foci in the pleura...
An 83-year-old man was diagnosed with tuberculous pleuroperitonitis on a thoracoscopic pleural biopsy. It may be due to endogenous reactivation of the foci in the pleura and peritoneum. Thoracoscopy, which can be performed under local anesthesia, should be considered when both pleural effusion and ascites are present.
PubMed: 35261775
DOI: 10.1002/ccr3.5530 -
The Cochrane Database of Systematic... Jan 2021Xpert MTB/RIF Ultra (Xpert Ultra) and Xpert MTB/RIF are World Health Organization (WHO)-recommended rapid nucleic acid amplification tests (NAATs) widely used for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Xpert MTB/RIF Ultra (Xpert Ultra) and Xpert MTB/RIF are World Health Organization (WHO)-recommended rapid nucleic acid amplification tests (NAATs) widely used for simultaneous detection of Mycobacterium tuberculosis complex and rifampicin resistance in sputum. To extend our previous review on extrapulmonary tuberculosis (Kohli 2018), we performed this update to inform updated WHO policy (WHO Consolidated Guidelines (Module 3) 2020).
OBJECTIVES
To estimate diagnostic accuracy of Xpert Ultra and Xpert MTB/RIF for extrapulmonary tuberculosis and rifampicin resistance in adults with presumptive extrapulmonary tuberculosis.
SEARCH METHODS
Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, 2 August 2019 and 28 January 2020 (Xpert Ultra studies), without language restriction.
SELECTION CRITERIA
Cross-sectional and cohort studies using non-respiratory specimens. Forms of extrapulmonary tuberculosis: tuberculous meningitis and pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, disseminated tuberculosis. Reference standards were culture and a study-defined composite reference standard (tuberculosis detection); phenotypic drug susceptibility testing and line probe assays (rifampicin resistance detection).
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias and applicability using QUADAS-2. For tuberculosis detection, we performed separate analyses by specimen type and reference standard using the bivariate model to estimate pooled sensitivity and specificity with 95% credible intervals (CrIs). We applied a latent class meta-analysis model to three forms of extrapulmonary tuberculosis. We assessed certainty of evidence using GRADE.
MAIN RESULTS
69 studies: 67 evaluated Xpert MTB/RIF and 11 evaluated Xpert Ultra, of which nine evaluated both tests. Most studies were conducted in China, India, South Africa, and Uganda. Overall, risk of bias was low for patient selection, index test, and flow and timing domains, and low (49%) or unclear (43%) for the reference standard domain. Applicability for the patient selection domain was unclear for most studies because we were unsure of the clinical settings. Cerebrospinal fluid Xpert Ultra (6 studies) Xpert Ultra pooled sensitivity and specificity (95% CrI) against culture were 89.4% (79.1 to 95.6) (89 participants; low-certainty evidence) and 91.2% (83.2 to 95.7) (386 participants; moderate-certainty evidence). Of 1000 people where 100 have tuberculous meningitis, 168 would be Xpert Ultra-positive: of these, 79 (47%) would not have tuberculosis (false-positives) and 832 would be Xpert Ultra-negative: of these, 11 (1%) would have tuberculosis (false-negatives). Xpert MTB/RIF (30 studies) Xpert MTB/RIF pooled sensitivity and specificity against culture were 71.1% (62.8 to 79.1) (571 participants; moderate-certainty evidence) and 96.9% (95.4 to 98.0) (2824 participants; high-certainty evidence). Of 1000 people where 100 have tuberculous meningitis, 99 would be Xpert MTB/RIF-positive: of these, 28 (28%) would not have tuberculosis; and 901 would be Xpert MTB/RIF-negative: of these, 29 (3%) would have tuberculosis. Pleural fluid Xpert Ultra (4 studies) Xpert Ultra pooled sensitivity and specificity against culture were 75.0% (58.0 to 86.4) (158 participants; very low-certainty evidence) and 87.0% (63.1 to 97.9) (240 participants; very low-certainty evidence). Of 1000 people where 100 have pleural tuberculosis, 192 would be Xpert Ultra-positive: of these, 117 (61%) would not have tuberculosis; and 808 would be Xpert Ultra-negative: of these, 25 (3%) would have tuberculosis. Xpert MTB/RIF (25 studies) Xpert MTB/RIF pooled sensitivity and specificity against culture were 49.5% (39.8 to 59.9) (644 participants; low-certainty evidence) and 98.9% (97.6 to 99.7) (2421 participants; high-certainty evidence). Of 1000 people where 100 have pleural tuberculosis, 60 would be Xpert MTB/RIF-positive: of these, 10 (17%) would not have tuberculosis; and 940 would be Xpert MTB/RIF-negative: of these, 50 (5%) would have tuberculosis. Lymph node aspirate Xpert Ultra (1 study) Xpert Ultra sensitivity and specificity (95% confidence interval) against composite reference standard were 70% (51 to 85) (30 participants; very low-certainty evidence) and 100% (92 to 100) (43 participants; low-certainty evidence). Of 1000 people where 100 have lymph node tuberculosis, 70 would be Xpert Ultra-positive and 0 (0%) would not have tuberculosis; 930 would be Xpert Ultra-negative and 30 (3%) would have tuberculosis. Xpert MTB/RIF (4 studies) Xpert MTB/RIF pooled sensitivity and specificity against composite reference standard were 81.6% (61.9 to 93.3) (377 participants; low-certainty evidence) and 96.4% (91.3 to 98.6) (302 participants; low-certainty evidence). Of 1000 people where 100 have lymph node tuberculosis, 118 would be Xpert MTB/RIF-positive and 37 (31%) would not have tuberculosis; 882 would be Xpert MTB/RIF-negative and 19 (2%) would have tuberculosis. In lymph node aspirate, Xpert MTB/RIF pooled specificity against culture was 86.2% (78.0 to 92.3), lower than that against a composite reference standard. Using the latent class model, Xpert MTB/RIF pooled specificity was 99.5% (99.1 to 99.7), similar to that observed with a composite reference standard. Rifampicin resistance Xpert Ultra (4 studies) Xpert Ultra pooled sensitivity and specificity were 100.0% (95.1 to 100.0), (24 participants; low-certainty evidence) and 100.0% (99.0 to 100.0) (105 participants; moderate-certainty evidence). Of 1000 people where 100 have rifampicin resistance, 100 would be Xpert Ultra-positive (resistant): of these, zero (0%) would not have rifampicin resistance; and 900 would be Xpert Ultra-negative (susceptible): of these, zero (0%) would have rifampicin resistance. Xpert MTB/RIF (19 studies) Xpert MTB/RIF pooled sensitivity and specificity were 96.5% (91.9 to 98.8) (148 participants; high-certainty evidence) and 99.1% (98.0 to 99.7) (822 participants; high-certainty evidence). Of 1000 people where 100 have rifampicin resistance, 105 would be Xpert MTB/RIF-positive (resistant): of these, 8 (8%) would not have rifampicin resistance; and 895 would be Xpert MTB/RIF-negative (susceptible): of these, 3 (0.3%) would have rifampicin resistance.
AUTHORS' CONCLUSIONS
Xpert Ultra and Xpert MTB/RIF may be helpful in diagnosing extrapulmonary tuberculosis. Sensitivity varies across different extrapulmonary specimens: while for most specimens specificity is high, the tests rarely yield a positive result for people without tuberculosis. For tuberculous meningitis, Xpert Ultra had higher sensitivity and lower specificity than Xpert MTB/RIF against culture. Xpert Ultra and Xpert MTB/RIF had similar sensitivity and specificity for rifampicin resistance. Future research should acknowledge the concern associated with culture as a reference standard in paucibacillary specimens and consider ways to address this limitation.
Topics: Adult; Antibiotics, Antitubercular; Bias; Drug Resistance, Bacterial; False Negative Reactions; False Positive Reactions; Humans; Mycobacterium tuberculosis; Nucleic Acid Amplification Techniques; Reagent Kits, Diagnostic; Rifampin; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Meningeal; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pleural
PubMed: 33448348
DOI: 10.1002/14651858.CD012768.pub3 -
The Journal of Experimental Medicine Mar 2022Orchestration of an effective T lymphocyte response at infection sites is critical for protection against Mycobacterium tuberculosis (Mtb) infection. However, the local...
Orchestration of an effective T lymphocyte response at infection sites is critical for protection against Mycobacterium tuberculosis (Mtb) infection. However, the local T cell immunity landscape in human tuberculosis is poorly defined. Tuberculous pleural effusion (TPE), caused by Mtb, is characterized by an influx of leukocytes to the pleural space, providing a platform suitable for delineating complex tissue responses to Mtb infection. Using single-cell transcriptomics and T cell receptor sequencing, we analyzed mononuclear cell populations in paired pleural fluid and peripheral blood of TPE patients. While all major cell clusters were present in both tissues, their relative proportions varied significantly by anatomic location. Lineage tracking analysis revealed subsets of CD8 and CD4 T cell populations with distinct effector functions specifically expanded at pleural sites. Granzyme K-expressing CD8 T cells were preferentially enriched and clonally expanded in pleural fluid from TPE, suggesting that they are involved in the pathogenesis of the disease. The findings collectively reveal the landscape of local T cell immunity in tuberculosis.
Topics: Biomarkers; Cell Differentiation; Disease Susceptibility; Gene Expression Profiling; Host-Pathogen Interactions; Humans; Immunophenotyping; Lymphocyte Activation; Lymphocyte Count; Mycobacterium tuberculosis; Pleural Effusion; Receptors, Antigen, T-Cell; Single-Cell Analysis; T-Lymphocyte Subsets; Tuberculosis
PubMed: 35061012
DOI: 10.1084/jem.20211777 -
Breathe (Sheffield, England) Dec 2023Pleural tuberculosis (TB) is a common entity with similar epidemiological characteristics to pulmonary TB. It represents a spectrum of disease that can variably... (Review)
Review
UNLABELLED
Pleural tuberculosis (TB) is a common entity with similar epidemiological characteristics to pulmonary TB. It represents a spectrum of disease that can variably self-resolve or progress to TB empyema with severe sequelae such as chronic fibrothorax or empyema necessitans. Coexistence of and progression to pulmonary TB is high. Diagnosis is challenging, as pleural TB is paucibacillary in most cases, but every effort should be made to obtain microbiological diagnosis, especially where drug resistance is suspected. Much attention has been focussed on adjunctive investigations to support diagnosis, but clinicians must be aware that apparent diagnostic accuracy is affected both by the underlying TB prevalence in the population, and by the diagnostic standard against which the specified investigation is being evaluated. Pharmacological treatment of pleural TB is similar to that of pulmonary TB, but penetration of the pleural space may be suboptimal in complicated effusions. Evidence for routine drainage is limited, but evacuation of the pleural space is indicated in complicated disease.
EDUCATIONAL AIMS
To demonstrate that pleural TB incorporates a wide spectrum of disease, ranging from self-resolving lymphocytic effusions to severe TB empyema with serious sequelae.To emphasise the high coexistence of pulmonary TB with pleural TB, and the importance of obtaining sputum for culture (induced if necessary) in all cases.To explore the significant diagnostic challenges posed by pleural TB, and consequently the frequent lack of information about drug sensitivity prior to initiating treatment.To highlight the influence of underlying TB prevalence in the population on the diagnostic accuracy of adjunctive investigations for the diagnosis of pleural TB.To discuss concerns around penetration of anti-TB medications into the pleural space and how this can influence decisions around treatment duration in practice.
PubMed: 38125799
DOI: 10.1183/20734735.0143-2023 -
Panminerva Medica Sep 2019Diseases of the pleura and pleural space are common and present a significant contribution to the workload of respiratory physicians, with most cases resulting from... (Review)
Review
Diseases of the pleura and pleural space are common and present a significant contribution to the workload of respiratory physicians, with most cases resulting from congestive heart failure, pneumonia, and cancer. Although the radiographic and ultrasonographic detection of pleural abnormalities may be obvious, the determination of a specific diagnosis can often represent a challenge. Invasive procedures such as pleural drainage, ultrasound/CT-guided pleural biopsy or medical thoracoscopy can be useful in determining specific diagnosis of pleural diseases. Management of primary and secondary spontaneous pneumothorax is mandatory in an interventional pulmonology training program, while the medical or surgical treatment of the recurrence is still a matter of discussion. Pleural drainage is a diagnostic and therapeutic procedure used in the treatment of pneumothorax and pleural effusions of different etiologies and even in palliation of symptomatic in malignant pleural effusion. Medical thoracoscopy (MT) is a minimally invasive procedure aimed at inspecting the pleural space. It could be a diagnostic procedure in pleural effusions (suspected malignant pleural effusion, infective pleural disease such as empyema or tuberculosis) or therapeutic procedure (chemical pleurodesis or opening of loculation in empyema). Diagnostic yield is 95% in patients with pleural malignancies and higher in pleural tuberculosis. In parapneumonic complex effusion, MT obviates the need for surgery in most cases. Thoracoscopy training should be considered being as important as bronchoscopy training for interventional pulmonology, although prior acquisition of ultrasonography and chest tube insertion skills is essential.
Topics: Bronchoscopy; Chest Tubes; Clinical Competence; Drainage; Humans; Minimally Invasive Surgical Procedures; Pleura; Pleural Effusion; Pleural Effusion, Malignant; Pneumonia; Pneumothorax; Pulmonary Medicine; Reproducibility of Results; Thoracoscopy
PubMed: 30394712
DOI: 10.23736/S0031-0808.18.03564-4 -
Interactive Cardiovascular and Thoracic... Jul 2022
Topics: Humans; Pleural Effusion; Pneumothorax; Pulmonary Edema
PubMed: 35751602
DOI: 10.1093/icvts/ivac170