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The Cochrane Database of Systematic... Aug 2018Tuberculosis (TB) is the world's leading infectious cause of death. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing, and over half a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculosis (TB) is the world's leading infectious cause of death. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing, and over half a million people were newly diagnosed with rifampicin-resistant TB in 2016. Xpert MTB/RIF (Xpert) is a World Health Organization (WHO)-recommended, rapid, automated, nucleic acid amplification assay that is used widely for simultaneous detection of Mycobacterium tuberculosis complex and rifampicin resistance in sputum specimens. This Cochrane Review assessed the accuracy of Xpert in extrapulmonary specimens.
OBJECTIVES
To determine the diagnostic accuracy of Xpert a) for extrapulmonary TB by site of disease in people presumed to have extrapulmonary TB; and b) for rifampicin resistance in people presumed to have extrapulmonary TB.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature (LILACS), Scopus, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number (ISRCTN) Registry, and ProQuest up to 7 August 2017 without language restriction.
SELECTION CRITERIA
We included diagnostic accuracy studies of Xpert in people presumed to have extrapulmonary TB. We included TB meningitis and pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, and disseminated TB. We used culture as the reference standard. For pleural TB, we also included a composite reference standard, which defined a positive result as the presence of granulomatous inflammation or a positive culture result. For rifampicin resistance, we used culture-based drug susceptibility testing or MTBDRplus as the reference standard.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, assessed risk of bias and applicability using the QUADAS-2 tool. We determined pooled predicted sensitivity and specificity for TB, grouped by type of extrapulmonary specimen, and for rifampicin resistance. For TB detection, we used a bivariate random-effects model. Recognizing that use of culture may lead to misclassification of cases of extrapulmonary TB as 'not TB' owing to the paucibacillary nature of the disease, we adjusted accuracy estimates by applying a latent class meta-analysis model. For rifampicin resistance detection, we performed univariate meta-analyses for sensitivity and specificity separately to include studies in which no rifampicin resistance was detected. We used theoretical populations with an assumed prevalence to provide illustrative numbers of patients with false positive and false negative results.
MAIN RESULTS
We included 66 unique studies that evaluated 16,213 specimens for detection of extrapulmonary TB and rifampicin resistance. We identified only one study that evaluated the newest test version, Xpert MTB/RIF Ultra (Ultra), for TB meningitis. Fifty studies (76%) took place in low- or middle-income countries. Risk of bias was low for patient selection, index test, and flow and timing domains and was high or unclear for the reference standard domain (most of these studies decontaminated sterile specimens before culture inoculation). Regarding applicability, in the patient selection domain, we scored high or unclear concern for most studies because either patients were evaluated exclusively as inpatients at tertiary care centres, or we were not sure about the clinical settings.Pooled Xpert sensitivity (defined by culture) varied across different types of specimens (31% in pleural tissue to 97% in bone or joint fluid); Xpert sensitivity was > 80% in urine and bone or joint fluid and tissue. Pooled Xpert specificity (defined by culture) varied less than sensitivity (82% in bone or joint tissue to 99% in pleural fluid and urine). Xpert specificity was ≥ 98% in cerebrospinal fluid, pleural fluid, urine, and peritoneal fluid.Xpert testing in cerebrospinal fluidXpert pooled sensitivity and specificity (95% credible interval (CrI)) against culture were 71.1% (60.9% to 80.4%) and 98.0% (97.0% to 98.8%), respectively (29 studies, 3774 specimens; moderate-certainty evidence).For a population of 1000 people where 100 have TB meningitis on culture, 89 would be Xpert-positive: of these, 18 (20%) would not have TB (false-positives); and 911 would be Xpert-negative: of these, 29 (3%) would have TB (false-negatives).For TB meningitis, ultra sensitivity and specificity against culture (95% confidence interval (CI)) were 90% (55% to 100%) and 90% (83% to 95%), respectively (one study, 129 participants).Xpert testing in pleural fluidXpert pooled sensitivity and specificity (95% CrI) against culture were 50.9% (39.7% to 62.8%) and 99.2% (98.2% to 99.7%), respectively (27 studies, 4006 specimens; low-certainty evidence).For a population of 1000 people where 150 have pleural TB on culture, 83 would be Xpert-positive: of these, seven (8%) would not have TB (false-positives); and 917 would be Xpert-negative: of these, 74 (8%) would have TB (false-negatives).Xpert testing in urineXpert pooled sensitivity and specificity (95% CrI) against culture were 82.7% (69.6% to 91.1%) and 98.7% (94.8% to 99.7%), respectively (13 studies, 1199 specimens; moderate-certainty evidence).For a population of 1000 people where 70 have genitourinary TB on culture, 70 would be Xpert-positive: of these, 12 (17%) would not have TB (false-positives); and 930 would be Xpert-negative: of these, 12 (1%) would have TB (false-negatives).Xpert testing for rifampicin resistanceXpert pooled sensitivity (20 studies, 148 specimens) and specificity (39 studies, 1088 specimens) were 95.0% (89.7% to 97.9%) and 98.7% (97.8% to 99.4%), respectively (high-certainty evidence).For a population of 1000 people where 120 have rifampicin-resistant TB, 125 would be positive for rifampicin-resistant TB: of these, 11 (9%) would not have rifampicin resistance (false-positives); and 875 would be negative for rifampicin-resistant TB: of these, 6 (1%) would have rifampicin resistance (false-negatives).For lymph node TB, the accuracy of culture, the reference standard used, presented a greater concern for bias than in other forms of extrapulmonary TB.
AUTHORS' CONCLUSIONS
In people presumed to have extrapulmonary TB, Xpert may be helpful in confirming the diagnosis. Xpert sensitivity varies across different extrapulmonary specimens, while for most specimens, specificity is high, the test rarely yielding a positive result for people without TB (defined by culture). Xpert is accurate for detection of rifampicin resistance. For people with presumed TB meningitis, treatment should be based on clinical judgement, and not withheld solely on an Xpert result, as is common practice when culture results are negative.
Topics: Antibiotics, Antitubercular; Bacterial Proteins; DNA-Directed RNA Polymerases; Drug Resistance, Bacterial; False Negative Reactions; False Positive Reactions; Humans; Mycobacterium tuberculosis; Reagent Kits, Diagnostic; Reference Standards; Rifampin; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Meningeal
PubMed: 30148542
DOI: 10.1002/14651858.CD012768.pub2 -
BMC Infectious Diseases Jun 2018Tuberculous pleurisy (TP) presents a diagnostic problem due to the limitations of traditional diagnostic methods. Different studies with the Xpert MTB/RIF assay have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculous pleurisy (TP) presents a diagnostic problem due to the limitations of traditional diagnostic methods. Different studies with the Xpert MTB/RIF assay have drawn variable conclusions about its values in TP diagnosis. We conducted a meta-analysis to assess whether the Xpert MTB/RIF assay is appropriate for the diagnosis of TP using pleural fluid samples.
METHODS
A systematic search of four literature databases in English and Chinese language was performed to identify studies involving the use of Xpert MTB/RIF in patients with TP confirmed by plural biopsy and/or mycobacterial culture. Pooled sensitivity, specificity and accordance proportion were calculated, and the forest plots were generated to assess the accuracy of Xpert MTB/RIF for TP diagnosis.
RESULTS
We identified 23 studies meeting our inclusion criteria. The pooled sensitivity and specificity of Xpert MTB/RIF were 30% (95% CI: 21-42%, I = 87.93%) and 99% (95% CI: 97-100%, I = 96.20%), respectively, and the area under the SROC curve (AUC) of Xpert MTB/RIF was 0.86 (95% CI: 0.83-0.89). Compared with drug susceptibility testing (DST), the pooled accordance rate of Xpert MTB/RIF in detecting rifampicin-susceptible cases and rifampicin-resistant cases was 99% (95% CI: 95-104%, I = 8.7%) and 94% (95% CI: 86-102%), respectively.
CONCLUSIONS
Our analysis suggests that the Xpert MTB/RIF assay is of limited value as a screening test for TP but has a high potential for confirming TP diagnosis and differentiating TP from non-TB diseases using pleural fluid samples.
Topics: Antibiotics, Antitubercular; Body Fluids; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Rifampin; Sensitivity and Specificity; Tuberculosis, Pleural
PubMed: 29940951
DOI: 10.1186/s12879-018-3196-4 -
Respiration; International Review of... 2018Tuberculosis (TB) is a rare cause of chylothorax. We describe a case and the results of a systematic review of all reported cases of TB-chylothorax. We identified 37... (Review)
Review
Tuberculosis (TB) is a rare cause of chylothorax. We describe a case and the results of a systematic review of all reported cases of TB-chylothorax. We identified 37 cases of TB-chylothorax. The symptoms at presentation were constitutional (85.7%; 30/35), dyspnea (60.6%; 20/33), and cough (54.5%; 18/33). Chylothorax developed subsequent to the diagnosis of TB in 27.8% (10/36) of the patients, after a median of 6.75 weeks (IQR 4-9). Chylothorax developed during an immune reconstitution syndrome (IRS) in 16.7% (10/36) of the patients, including immunocompetent ones. TB was disseminated in 45.9% (17/37) of the patients at the diagnosis of chylothorax. Chylothorax developed in the absence of any mediastinal lymphadenopathy in 45.9% (17/37) of the patients; 13.5% (5/37) had isolated tubercular empyema alone. The diagnosis of TB was established microbiologically in 72.2% (26/36) and by biopsy alone in 27.8% (9/36) of the patients. Anti-TB treatment (ATT) was administered for a median of 7.57 months (IQR 6-9). Steroids were administered to 22.9% (8/35) of the patients, often for suspected IRS. Thoracic duct ligation and octreotide were required for only 17.1% (6/35) and 8.6% (3/35) of the patients, respectively. In all, 94.4% (34/36) of the patients had resolution of chylothorax and completed treatment successfully; only 5.6% (2/36) died. In conclusion, TB-chylothorax may develop without obvious mediastinal lymphadenopathy and be associated with tubercular empyema alone. TB-chylothorax can develop during treatment of TB due to IRS, even in immunocompetent patients. ATT and dietary manipulation are associated with good resolution and low mortality, and duct ligation is needed for only a small minority of patients.
Topics: Chylothorax; Humans; Male; Middle Aged; Radiography, Thoracic; Tomography, X-Ray Computed; Tuberculosis
PubMed: 29316546
DOI: 10.1159/000484694 -
BMC Pulmonary Medicine Dec 2017The ability of interleukins (ILs) to differentiate tuberculous pleural effusion from other types of effusion is controversial. The aim of our study was to summarize the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The ability of interleukins (ILs) to differentiate tuberculous pleural effusion from other types of effusion is controversial. The aim of our study was to summarize the evidence for its use of ruling out or in tuberculous pleural effusion.
METHODS
Two investigators independently searched PubMed, EMBASE, Web of Knowledge, CNKI, WANFANG, and WEIPU databases to identify studies assessing diagnostic role of ILs for tuberculous pleural effusion published up to January, 2017. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. The pooled diagnostic sensitivity and specificity of ILs were calculated by using Review Manager 5.3. Area under the summary receiver operating characteristic curve (AUC) was used to summarize the overall diagnostic performance of individual markers.
RESULTS
Thirty-eight studies met our inclusion criteria. Pooled sensitivity, specificity and AUC for chosen ILs were as follows: IL-2, 0.67,0.76 and 0.86; IL-6, 0.86, 0.84 and 0.90; IL-12, 0.78, 0.83 and 0.86; IL-12p40, 0.82,0.65 and 0.76; IL-18, 0.87, 0.92 and 0.95; IL-27, 0.93, 0.95 and 0.95; and IL-33, 0.84, 0.80 and 0.88.
CONCLUSIONS
Some of these ILs may assist in diagnosing tuberculous pleural effusion, though no single IL is likely to show adequate sensitivity or specificity on its own. Further studies on a large scale with better study design should be performed to assess the diagnostic potential of ILs.
Topics: Area Under Curve; Exudates and Transudates; Humans; Interleukins; Pleural Effusion; Sensitivity and Specificity; Tuberculosis, Pleural
PubMed: 29216864
DOI: 10.1186/s12890-017-0530-3 -
The Cochrane Database of Systematic... Mar 2017Corticosteroids used in addition to antituberculous therapy have been reported to benefit people with tuberculous pleurisy. However, research findings are inconsistent... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Corticosteroids used in addition to antituberculous therapy have been reported to benefit people with tuberculous pleurisy. However, research findings are inconsistent and raise doubt as to whether such treatment is worthwhile. There is also concern regarding the potential adverse effects of corticosteroids, especially in HIV-positive people.
OBJECTIVES
To evaluate the effects of adding corticosteroids to drug regimens for tuberculous pleural effusion.
SEARCH METHODS
In April 2016, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE, Embase, LILACS, Current Controlled Trials, and the reference lists of articles identified by the literature search.
SELECTION CRITERIA
Randomized controlled trials (RCTs) and quasi-RCTs that compared any corticosteroid with no treatment, placebo, or other active treatment (both groups should have received the same antituberculous drug regimen) in people diagnosed with tuberculous pleurisy.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results, extracted data from the included trials, and assessed trial methodological quality using the Cochrane 'Risk of bias' tool. We analysed the data using risk ratios (RR) with 95% confidence intervals (CIs). We applied the fixed-effect model in the absence of statistically significant heterogeneity.
MAIN RESULTS
Six trials with 590 participants met the inclusion criteria, which were conducted in Asia (three trials), Africa (two trials), and Europe (one trial). Two trials were in HIV-negative people, one trial was in HIV-positive people, and three trials did not report HIV status.Corticosteroids may reduce the time to resolution of pleural effusion. Risk of residual pleural effusion on chest X-ray was reduced by 45% at eight weeks (RR 0.54, 95% CI 0.37 to 0.78; 237 participants, 2 trials, low certainty evidence), and 65% at 24 weeks (RR 0.35, 95% CI 0.18 to 0.66; 237 participants, 2 trials, low certainty evidence).Compared with control, corticosteroids may reduce the risk of having pleural changes (such as pleural thickening or pleural adhesions), on chest X-ray at the end of follow-up by almost one third (RR 0.72, 95% CI 0.57 to 0.92; 393 participants, 5 trials,low certainty evidence), which translates to an absolute risk reduction of 16%.One trial reported deaths in people that were HIV-positive, with no obvious difference between the groups; the trial authors' analysis suggests that the deaths observed in this trial were related to HIV disease rather than pleural TB (RR 0.91, 95% CI 0.64 to 1.31; 197 participants, 1 trial).We found limited data on long-term functional respiratory impairment on 187 people in two trials, which reported that average percentage predicted forced vital capacity was similar in the group receiving prednisolone and in the control group (very low certainty evidence).The risk of adverse events that led to discontinuation of the trial drug was higher in people with pleural TB receiving corticosteroids (RR 2.78, 95% CI 1.11 to 6.94; 587 participants, 6 trials, low certainty evidence). The trial in HIV-positive people reported on six different HIV-related infections, with no obvious differences. However, cases of Kaposi's sarcoma were only seen in the corticosteroid group (with 6/99 cases in the steroid group compared to 0/98 in the control group) (very low certainty evidence).
AUTHORS' CONCLUSIONS
Long-term respiratory function is potentially the most important outcome for assessing the effects of adjunctive treatments for people with pleural TB. However, the information on the impact of pleural TB on long-term respiratory function is unknown and could be eclipsed by other risk factors, such as concurrent pulmonary TB, smoking, and HIV. This probably needs to be quantified to help decide whether further trials of corticosteroids for pleural TB would be worthwhile.
Topics: Adrenal Cortex Hormones; Antitubercular Agents; HIV Seronegativity; HIV Seropositivity; Humans; Pleura; Randomized Controlled Trials as Topic; Tuberculosis, Pleural; Tuberculosis, Pulmonary
PubMed: 28290161
DOI: 10.1002/14651858.CD001876.pub3 -
Journal of Thoracic Disease Aug 2016Pseudochylothorax (PCT) (cholesterol pleurisy or chyliform effusion) is a cholesterol-rich pleural effusion (PE) that is commonly associated with chronic inflammatory...
BACKGROUND
Pseudochylothorax (PCT) (cholesterol pleurisy or chyliform effusion) is a cholesterol-rich pleural effusion (PE) that is commonly associated with chronic inflammatory disorders. Nevertheless, the characteristics of patients with PCT are poorly defined.
METHODS
A systematic review was performed across two electronic databases searching for studies reporting clinical findings, PE characteristics, and the most effective treatment of PCT. Case descriptions and retrospective studies were included.
RESULTS
The review consisted of 62 studies with a total of 104 patients. Median age was 58 years, the male/female ratio was 2.6/1, and in the 88.5% of cases the etiology was tuberculosis (TB) or rheumatoid arthritis (RA). PE was usually unilateral (88%) and occupied greater than one-third of the hemithorax (96.3%). There was no evidence of pleural thickening in 20.6% of patients, and 14 patients had a previous PE. The pleural fluid (PF) was an exudate, usually milky (94%) and with a predominance of lymphocytes (61.1%). The most sensitive tests to establish the diagnosis were the cholesterol/triglycerides ratio (CHOL/TG ratio) >1, and the presence of cholesterol crystals (97.4% and 89.7%, respectively). PF culture for TB was positive in the 34.1% of patients. Favorable outcomes with medical treatment, therapeutic thoracentesis, decortication/pleurectomy, pleurodesis, thoracic drainage and thoracoscopic drainage were achieved in 78.9%, 47.8%, 86.7%, 66.6%, 37.5% and 42.9%, respectively.
CONCLUSIONS
PCT is usually tuberculous or rheumatoid, unilateral and the PF is a milky exudate. The presence of cholesterol crystals and a CHOL/TG ratio >1 are the most sensitive test for the diagnosis. The lack of pleural thickening does not rule out PCT. Treatment should be sequential, treating the underlying causes, and assessing the need for interventional techniques.
PubMed: 27621864
DOI: 10.21037/jtd.2016.07.84 -
PloS One 2016Tuberculosis is an important risk factor for chronic respiratory disease in resource poor settings. The persistence of abnormal spirometry and symptoms after treatment... (Review)
Review
BACKGROUND
Tuberculosis is an important risk factor for chronic respiratory disease in resource poor settings. The persistence of abnormal spirometry and symptoms after treatment are well described, but the structural abnormalities underlying these changes remain poorly defined, limiting our ability to phenotype post-TB lung disease in to meaningful categories for clinical management, prognostication, and ongoing research. The relationship between post-TB lung damage and patient-centred outcomes including functional impairment, respiratory symptoms, and health related quality of life also remains unclear.
METHODS
We performed a systematic literature review to determine the prevalence and pattern of imaging-defined lung pathology in adults after medical treatment for pleural, miliary, or pulmonary TB disease. Data were collected on study characteristics, and the modality, timing, and findings of thoracic imaging. The proportion of studies relating imaging findings to spirometry results and patient morbidity was recorded. Study quality was assessed using a modified Newcastle-Ottowa score. (Prospero Registration number CRD42015027958).
RESULTS
We identified 37 eligible studies. The principle features seen on CXR were cavitation (8.3-83.7%), bronchiectasis (4.3-11.2%), and fibrosis (25.0-70.4%), but prevalence was highly variable. CT imaging identified a wider range of residual abnormalities than CXR, including nodules (25.0-55.8%), consolidation (3.7-19.2%), and emphysema (15.0-45.0%). The prevalence of cavitation was generally lower (7.4-34.6%) and bronchiectasis higher (35.0-86.0%) on CT vs. CXR imaging. A paucity of prospective data, and data from HIV-infected adults and sub-Saharan Africa (sSA) was noted. Few studies related structural damage to physiological impairment, respiratory symptoms, or patient morbidity.
CONCLUSIONS
Post-TB structural lung pathology is common. Prospective data are required to determine the evolution of this lung damage and its associated morbidity over time. Further data are required from HIV-infected groups and those living in sSA.
Topics: Humans; Image Processing, Computer-Assisted; Pattern Recognition, Automated; Prevalence; Tomography, X-Ray Computed; Tuberculosis, Pulmonary; United Kingdom
PubMed: 27518438
DOI: 10.1371/journal.pone.0161176 -
Journal of Clinical Microbiology Feb 2016
PubMed: 26822772
DOI: 10.1128/JCM.03178-15 -
Journal of Clinical Microbiology Apr 2016A systematic review investigating the role of Xpert MTB/RIF in the diagnosis of tuberculous pleural effusion (TPE) was conducted. The pooled sensitivities and... (Meta-Analysis)
Meta-Analysis Review
A systematic review investigating the role of Xpert MTB/RIF in the diagnosis of tuberculous pleural effusion (TPE) was conducted. The pooled sensitivities and specificities of Xpert MTB/RIF were 51.4% and 98.6%, respectively, with culture used as a reference standard and 22.7% and 99.8%, respectively, with a composite reference standard (CRS) used as the benchmark. Xpert MTB/RIF has low sensitivity but excellent specificity in the diagnosis of TPE.
Topics: Antitubercular Agents; Drug Resistance, Bacterial; Humans; Molecular Diagnostic Techniques; Mycobacterium tuberculosis; Pleural Effusion; Rifampin; Sensitivity and Specificity; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pleural
PubMed: 26818675
DOI: 10.1128/JCM.03205-15 -
Journal of Clinical Microbiology Aug 2015The role of interferon gamma release assays (IGRAs), although established for identifying latent tuberculosis, is still evolving in the diagnosis of active... (Meta-Analysis)
Meta-Analysis Review
The role of interferon gamma release assays (IGRAs), although established for identifying latent tuberculosis, is still evolving in the diagnosis of active extrapulmonary tuberculosis. We systematically evaluated the diagnostic performance of blood- and pleural fluid-based IGRAs in tuberculous pleural effusion (TPE). We searched the PubMed and Embase databases for studies evaluating the use of commercially available IGRAs on blood and/or pleural fluid samples for diagnosing TPE. The quality of the studies included was assessed through the QUADAS-2 tool. The pooled estimates of sensitivity and specificity with 95% confidence intervals (95% CI) were generated using a bivariate random-effects model and examined using forest plots and hierarchical summary receiver operating characteristic (HSROC) curves. Indeterminate IGRA results were included for sensitivity calculations. Heterogeneity was explored through subgroup analysis and meta-regression based on prespecified covariates. We identified 19 studies assessing the T.SPOT.TB and/or QuantiFERON assays. There were 20 and 14 evaluations, respectively, of whole-blood and pleural fluid assays, involving 1,085 and 727 subjects, respectively. There was only one good-quality study, and five studies used nonstandard assay thresholds. The pooled sensitivity and specificity for the blood assays were 0.77 (95% CI, 0.71 to 0.83) and 0.71 (95% CI, 0.65 to 0.76), respectively. The pooled sensitivity and specificity for the pleural fluid assays were 0.72 (95% CI, 0.55 to 0.84) and 0.78 (95% CI, 0.65 to 0.87), respectively. There was considerable heterogeneity; however, multivariate meta-regression did not identify any covariate with significant influence. There was no publication bias for blood assays. We conclude that commercial IGRAs, performed either on whole-blood or pleural fluid samples, have poor diagnostic accuracy in patients suspected to have TPE.
Topics: Antigens, Bacterial; Blood; Diagnostic Tests, Routine; Humans; Interferon-gamma Release Tests; Pleural Effusion; ROC Curve; Sensitivity and Specificity; Tuberculosis, Pleural
PubMed: 25994163
DOI: 10.1128/JCM.00823-15