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Journal of Clinical Laboratory Analysis Jan 2022Tuberculosis poses a severe threat to human health. At present, compared with the traditional diagnostic methods for tuberculosis pleural effusion, such as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis poses a severe threat to human health. At present, compared with the traditional diagnostic methods for tuberculosis pleural effusion, such as Löwenstein-Jensen culture, pleural biopsy, and Ziehl-Neelsen smear microscopy, Xpert MTB/RIF was regarded as an emerging technology for its efficiency. The Xpert MTB/RIF accuracy for tuberculous pleural effusion diagnosis was evaluated in this systematic study.
MATERIALS AND METHODS
We searched the relevant literature published before January 2021 in PubMed, Cochrane, EMBASE, and Web of Science databases. Utilizing Review Manager 5.3 software, the quality of the included literature was evaluated based on the Quality Assessment of Diagnostic Accuracy Studies criteria. Sensitivity, specificity, and the summary receiver operating characteristic curves were plotted and analyzed with Metadisc 1.40 software. We used Stata 12.0 software to evaluate the publication bias of this study.
RESULTS
Eighteen articles were identified in total. The sensitivity of Xpert MTB/RIF in the pleural effusion was 0.24, and specificity was 1.00, respectively. The area under the summary receiver operating characteristic curve was 0.9737, which indicated that the overall accuracy of the Xpert MTB/RIF was high. In addition, based on the Deeks funnel plot, no publication bias of the study was found.
CONCLUSION
Xpert MTB/RIF is a rapid method with high specificity but relatively low sensitivity for detecting Mycobacterium tuberculosis in pleural effusion. Its less sensitivity made it difficult to be used clinically, but the high specificity suggests that it can be used as a specific diagnostic method for tuberculous pleural effusion.
Topics: Humans; Mycobacterium tuberculosis; Nucleic Acid Amplification Techniques; Pleural Effusion; ROC Curve; Reference Standards; Sensitivity and Specificity; Tuberculosis
PubMed: 34919739
DOI: 10.1002/jcla.24185 -
International Journal of... 2022Tuberculous meningitis (TBM) is the most common and serious form of central nervous system tuberculosis (TB) with high morbidity and mortality. Following the encounter... (Review)
Review
BACKGROUND
Tuberculous meningitis (TBM) is the most common and serious form of central nervous system tuberculosis (TB) with high morbidity and mortality. Following the encounter of tubercle bacilli by microglial cells, inflammatory process sets in and series of cytokines are secreted such as tumor necrosis factor, interleukin-6 (IL6), and interferon γ. The following study was undertaken with the aim of systemically reviewing the diagnostic and prognostic evidence of IL6 in TBM.
METHODS
After a thorough search of databases for the articles with IL6 association in TBM published from 2001 onwards to September 2021. Articles were identified and assessed according to the inclusion and exclusion criteria. Excel spreadsheets were used for the extraction of data and analysis.
RESULTS
A total of 10 studies were included for review which focused on IL6 in the role of TBM diagnosis. All the age group persons of both sexes were included in the study. The experiment was conducted mostly in the developing countries. The range of measured IL6 values was very wide and difficult to interpret.
CONCLUSION
TBM patients' IL 6 was higher than healthy controls in all the studies mentioned, but the results of cerebrospinal fluid IL6 and serum IL6 were less consistent. Due to a small number of prospective studies, it was not possible to analyze the IL6 cut-off value to diagnose TB. Further studies are required to provide information on IL6 as biomarker in the diagnosis of TBM.
Topics: Male; Female; Humans; Tuberculosis, Meningeal; Interleukin-6; Prospective Studies; Interferon-gamma; Mycobacterium tuberculosis; Biomarkers; Cytokines; Tumor Necrosis Factors
PubMed: 36260439
DOI: 10.4103/ijmy.ijmy_101_22 -
BMC Infectious Diseases Aug 2020In sub-Saharan Africa (SSA), most prisons are overcrowded with poor ventilation and put prisoners disproportionally at risk of exposure to Mycobacterium tuberculosis...
BACKGROUND
In sub-Saharan Africa (SSA), most prisons are overcrowded with poor ventilation and put prisoners disproportionally at risk of exposure to Mycobacterium tuberculosis (TB) and developing TB infection but are mostly missed due to poor access to healthcare. Active case-finding (ACF) of TB in prisons facilitates early diagnosis and treatment of inmates and prevent the spread. We explored literature and described evidence on TB ACF interventions and approaches for prisoners in SSA prisons.
METHODS
Guided by the Arksey and O'Malley framework, we searched PubMed, Google Scholar, SCOPUS, Academic search complete, CINAHL and MEDLINE with full text via EBSCOhost for articles on prisoners and ACF from 2000 to May 2019 with no language restriction. Two investigators independently screened the articles at the abstract and full-text stages in parallel guided by the eligibility criteria as well as performed the methodological quality appraisal of the included studies using the latest mixed-method appraisal tool. We extracted all relevant data, organized them into themes and sub-themes, and presented a narrative summary of the results.
RESULTS
Of the 391 eligible articles found, 31 met the inclusion criteria. All 31 articles were published between 2006 and 2019 with the highest six (19.4%) in 2015. We found evidence in 11 countries. That is, Burkina Faso, Cameroon, Coˆte d'Ivoire, the Democratic Republic of the Congo, Ethiopia, Ghana, Malawi, Nigeria, South Africa, Uganda, and Zambia with most 41.9% (13/31) recorded in Ethiopia. These intervention studies were conducted in 134 prisons between 2001 and 2018 using either a single or combination of mass, facility-led, entry, peer educators for routine screening, and exit ACF approaches. The majority (74%) of the studies utilized only a mass screening approach. The most (68%) reported study outcome was smear-positive TB cases only (68%). We found no evidence in 16 SSA countries although they are classified among the three high-burden country lists for TB TB/HIV and Multidrug resistant-TB group.
CONCLUSION
Our review highlights a dearth of evidence on TB ACF interventions in most SSA countries prisons. Hence, there is the need to scaling-up ACF interventions in SSA prisons, particularly countries included in the three high-burden country lists for TB, TB/HIV, and MDR-TB.
Topics: Africa South of the Sahara; Antibiotics, Antitubercular; Drug Resistance, Multiple, Bacterial; Female; Humans; Male; Mass Screening; Mycobacterium tuberculosis; Nucleic Acid Amplification Techniques; Prevalence; Prisoners; Rifampin; Sputum; Tuberculin Test; Tuberculosis, Multidrug-Resistant
PubMed: 32758165
DOI: 10.1186/s12879-020-05283-1 -
Antimicrobial Agents and Chemotherapy Feb 2021Molecular testing is rapidly becoming an integral component of global tuberculosis (TB) control. Uncommon mechanisms of resistance escape detection by these platforms...
Systematic Review of Mutations Associated with Isoniazid Resistance Points to Continuing Evolution and Subsequent Evasion of Molecular Detection, and Potential for Emergence of Multidrug Resistance in Clinical Strains of Mycobacterium tuberculosis.
Molecular testing is rapidly becoming an integral component of global tuberculosis (TB) control. Uncommon mechanisms of resistance escape detection by these platforms and undermine our ability to contain outbreaks. This article is a systematic review of published articles that reported isoniazid (INH) resistance-conferring mutations between September 2013 and December 2019. The genes , , and , and the intergenic region '- were considered in this review. Fifty-two articles were included that described 9,306 clinical isolates (5,804 INH resistant [INH] and 3,502 INH susceptible [INH]) from 31 countries. The three most frequently mutated loci continue to be locus 315 of (315; = 4,271), locus -15 of (-15; = 787), and locus -8 of (-8; 106). However, the diagnostic value of -8 is far lower than previously thought, as it only appears in 25 (0.4%) of the INH isolates lacking the first two mutations. I catalogued 45 new loci (29 , nine , and seven ) associated with INH resistance and identified 59 loci (common to this and previous reviews) as a reliable basis for molecular diagnostics. Including all observed mutations provides a cumulative sensitivity of 85.6%. In 14.4% of resistant isolates, no mechanism of resistance was detected, making them likely to escape molecular detection, and in the case of INH monoresistance, likely to convert to multidrug-resistant TB (MDR-TB). Integrating the information cataloged in this study into current diagnostic tools is essential for combating the emergence of MDR-TB, and its exclusion can lead to an unintended selection against common mechanisms and to diversifying evolution. Observation of many low-frequency resistance-conferring mutations points to an advantage of whole-genome sequencing (WGS) for diagnostics. Finally, I provide five recommendations for future diagnostic platforms.
Topics: Antitubercular Agents; Bacterial Proteins; DNA, Bacterial; Drug Resistance, Multiple; Humans; Isoniazid; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 33361298
DOI: 10.1128/AAC.02091-20 -
The Lancet. Infectious Diseases Jun 2020The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M... (Meta-Analysis)
Meta-Analysis
Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data.
BACKGROUND
The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI.
METHODS
We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022.
FINDINGS
We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per μL (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05-3·08) but not after 30 days (1·25, 0·84-2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16-8·84).
INTERPRETATION
In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients.
FUNDING
This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A.
Topics: Bacteremia; HIV Infections; Humans; Mortality; Mycobacterium tuberculosis; Prevalence; Tuberculosis
PubMed: 32178764
DOI: 10.1016/S1473-3099(19)30695-4 -
The Lancet. Global Health Jan 2024Tuberculosis is a leading cause of infectious disease mortality worldwide, but diagnosis of pulmonary tuberculosis remains challenging. Oral swabs are a promising...
BACKGROUND
Tuberculosis is a leading cause of infectious disease mortality worldwide, but diagnosis of pulmonary tuberculosis remains challenging. Oral swabs are a promising non-sputum alternative sample type for the diagnosis of pulmonary tuberculosis. We aimed to assess the diagnostic accuracy of oral swabs to detect pulmonary tuberculosis in adults and children and suggest research implications.
METHODS
In this systematic review, we searched published and preprint studies from Jan 1, 2000, to July 5, 2022, from eight databases (MEDLINE, Embase, Scopus, Science Citation Index, medRxiv, bioRxiv, Global Index Medicus, and Google Scholar). We included diagnostic accuracy studies including cross-sectional, cohort, and case-control studies in adults and children from which we could extract or derive sensitivity and specificity of oral swabs as a sample type for the diagnosis of pulmonary tuberculosis against a sputum microbiological (nucleic acid amplification test [NAAT] on sputum or culture) or composite reference standard.
FINDINGS
Of 550 reports identified by the search, we included 16 eligible reports (including 20 studies and 3083 participants) that reported diagnostic accuracy estimates on oral swabs for pulmonary tuberculosis. Sensitivity on oral swabs ranged from 36% (95% CI 26-48) to 91% (80-98) in adults and 5% (1-14) to 42% (23-63) in children. Across all studies, specificity ranged from 66% (95% CI 52-78) to 100% (97-100), with most studies reporting specificity of more than 90%. Meta-analysis was not performed because of sampling and testing heterogeneity.
INTERPRETATION
Sensitivity varies in both adults and children when diverse methods are used. Variability in sampling location, swab type, and type of NAAT used in accuracy studies limits comparison. Although data are suggestive that high accuracy is achievable using oral swabs with molecular testing, more research is needed to define optimal methods for using oral swabs as a specimen for tuberculosis detection. The current data suggest that tongue swabs and swab types that collect increased biomass might have increased sensitivity. We would recommend that future studies use these established methods to continue to refine sample processing to maximise sensitivity.
FUNDING
Bill and Melinda Gates foundation (INV-045721) and FIND (Netherlands Enterprise Agency on behalf of the Minister for Foreign Trade and Development Cooperation [NL-GRNT05] and KfW Development Bank, German Federal Ministry of Education and Research [KFW-TBBU01/02]).
Topics: Adult; Child; Humans; Mycobacterium tuberculosis; Cross-Sectional Studies; Pathology, Molecular; Tuberculosis, Pulmonary; Tuberculosis; Sensitivity and Specificity; Molecular Diagnostic Techniques
PubMed: 38097297
DOI: 10.1016/S2214-109X(23)00469-2 -
PloS One 2020Abdominal tuberculosis is a severe extrapulmonary tuberculosis, which can lead to serious complications. Early diagnosis and treatment are very important for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Abdominal tuberculosis is a severe extrapulmonary tuberculosis, which can lead to serious complications. Early diagnosis and treatment are very important for the prognosis and the diagnosis of abdominal tuberculosis is still difficult. This study aims to evaluate the diagnostic accuracy of nucleic acid amplification tests (NAATs) for abdominal tuberculosis using meta-analysis method.
METHODS
We will search PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure, and the Wanfang database for studies evaluating the diagnostic accuracy of NAATs for abdominal tuberculosis until May 2020. We will include a systematic review and meta-analysis that evaluated the accuracy of NAATs for abdominal tuberculosis. Any types of study design with full text will be sought and included. The risk of bias will be assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Stata version 15.0 with the midas command packages will be used to carry out meta-analyses.
RESULTS
The results will provide clinical evidence for diagnostic accuracy of NAATs for abdominal tuberculosis, and this systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication.
CONCLUSION
This overview will provide evidence of NAATs for diagnosis of abdominal tuberculosis.
SYSTEMATIC REVIEW REGISTRATION
INPLASY202060030.
Topics: Abdomen; DNA, Bacterial; Databases, Factual; Humans; Mycobacterium tuberculosis; Nucleic Acid Amplification Techniques; Reference Standards; Tuberculosis
PubMed: 33315919
DOI: 10.1371/journal.pone.0243765 -
BMC Infectious Diseases Jun 2023Individuals in close contact with active pulmonary tuberculosis (TB) patients showed a high risk of recent infection and, once infected, higher risk of developing active... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Individuals in close contact with active pulmonary tuberculosis (TB) patients showed a high risk of recent infection and, once infected, higher risk of developing active TB in the following years post-exposure. But the peak time of active disease onset is unclear. This study aims to estimate post exposure TB incidence risk among close contacts to provide reference for clinical and public health strategies.
METHODS
We searched PubMed, Web of Science, and EMBASE for articles published until December 1, 2022. The incidence rates were quantitatively summarized by means of meta-analysis using the random-effect model.
RESULTS
Of the 5616 studies, 31 studies included in our analysis. For baseline close contacts results, the summarized prevalence of Mycobacterium tuberculosis (MTB) infection and active TB was found to be 46.30% (95% CI: 37.18%-55.41%) and 2.68% (95% CI: 2.02%-3.35%), respectively. During the follow-up, the 1-year, 2-year and 5-year cumulative incidence of TB in close contacts were 2.15% (95% CI: 1.51%-2.80%), 1.21% (95% CI: 0.93%-1.49%) and 1.11% (95% CI: 0.64%-1.58%), respectively. Individuals with a positive result of MTB infection testing at baseline showed significantly higher cumulative TB incidence as compared to those negatives (3.80% vs. 0.82%, p < 0.001).
CONCLUSIONS
Individuals with close contact to active pulmonary TB patients are bearing significant risk of developing active TB, particularly within the first-year post-exposure. Population with recent infections should be an important priority for active case finding and preventive intervention worldwide.
Topics: Humans; Incidence; Contact Tracing; Tuberculosis; Tuberculosis, Pulmonary; Mycobacterium tuberculosis
PubMed: 37270474
DOI: 10.1186/s12879-023-08348-z -
The Lancet. Infectious Diseases Sep 2020Suboptimal diagnostics for pulmonary tuberculosis drive the use of the so-called trial of antibiotics, a course of broad-spectrum antibiotics without activity against... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Suboptimal diagnostics for pulmonary tuberculosis drive the use of the so-called trial of antibiotics, a course of broad-spectrum antibiotics without activity against Mycobacterium tuberculosis that is given to patients who are mycobacteriology negative but symptomatic, with the aim of distinguishing pulmonary tuberculosis from bacterial lower respiratory tract infection. The underlying assumption-that patients with lower respiratory tract infection will improve, whereas those with pulmonary tuberculosis will not-has an unclear evidence base for such a widely used intervention (at least 26·5 million courses are prescribed per year). We aimed to collate available evidence on the diagnostic performance of the trial of antibiotics.
METHODS
In this systematic review and meta-analysis we searched the MEDLINE, Embase, and Global Health databases for studies published up to March 15, 2019, that investigated the sensitivity and specificity of the trial of antibiotics against mycobacteriology tests in adults (≥15 years) with tuberculosis symptoms. We used the QUADAS-2 tool to assess the risk of bias. We estimated pooled values for sensitivity and specificity of trial of antibiotics (as the index text) versus mycobacteriology tests (as the reference standard) using random-effects bivariate modelling, and we used the I statistic to assess heterogeneity between studies contributing to these estimates. This study is registered with PROSPERO, number CRD42017083915.
FINDINGS
Of the 9410 articles identified by our search, eight studies were eligible for inclusion. The studies were from seven countries in Africa, South America, and Asia, and involved 2786 participants. Six studies used mycobacterial culture as the reference standard, and six used penicillins for the trial of antibiotics. The treatment duration, number of antimicrobial courses, and definition of what constituted response to treatment varied substantially between studies. The pooled sensitivity (67%, 95% CI 42-85) and specificity (73%, 58-85) of the trial of antibiotics versus mycobacteriology tests were below internationally defined minimum performance profiles for tuberculosis diagnostics and had substantial heterogeneity (I was 96% for sensitivity and 99% for specificity). Each included study failed on one or more domain of the QUADAS-2 tool.
INTERPRETATION
Current policy and practice regarding the trial of antibiotics appear inappropriate, given the weak evidence base, poor diagnostic performance, potential contribution to the global antimicrobial resistance crisis, and adverse individual and public health consequences from the misclassification of tuberculosis status. Antibiotic strategies during tuberculosis investigations should instead optimise clinical outcomes, ideally guided by clinical trials in both inpatient and outpatient groups.
FUNDING
Helse Nord RHF, Wellcome Trust, and the UK Commonwealth Scholarship Commission.
Topics: Adult; Anti-Bacterial Agents; Coinfection; HIV Infections; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; ROC Curve; Sensitivity and Specificity; Tuberculosis, Pulmonary
PubMed: 32437700
DOI: 10.1016/S1473-3099(20)30143-2 -
Journal of Global Antimicrobial... Sep 2022Dapsone is one of the important drugs in the treatment of leprosy. The present study aims to evaluate the resistance of Mycobacterium leprae isolates to dapsone, in turn... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Dapsone is one of the important drugs in the treatment of leprosy. The present study aims to evaluate the resistance of Mycobacterium leprae isolates to dapsone, in turn assisting in implementing better control strategies for leprosy elimination.
METHODS
A systematic literature search was conducted in PubMed, Embase, Medline, and Web of Science. Two independent reviewers selected the literature according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), extracted data, and evaluated the risk of bias. Drug resistance data were pooled using the random-effects model. Subgroup analysis was performed based on across sampling time, region, study population (treatment status, relapses status), and sample size.
RESULTS
A total of 30 studies were included. The results of meta-analysis showed that the dapsone resistance rate of leprosy patients after treatment was 8% (95% confidence interval [CI], 6%-10%). Compared to the rates of primary resistance of new cases without treatment therapy (pooled incidence, 4% [95% CI, 2%-5%]), treatment cases (13% [95% CI 9%-16%]) had secondary resistance, and relapse cases (26% [95% CI, 18%-33%]) had drug resistance. In addition, the drug resistance rate of monotherapy was significantly increased than that of relapsed patients treated with diamino-diphenylsulfone monotherapy. Subgroup analysis showed that the patients in the Western Pacific have the highest dapsone resistance, and the resistance to dapsone was slightly lower after 2005. For sample size, the rate in the group under 100 samples was significantly higher than in the other.
CONCLUSION
Dapsone resistance is closely related to leprosy relapse and long-term drug use. Dapsone monotherapy is one of important reasons for drug resistance in relapsed cases. Drug resistance varies among different populations and regions of the world.
Topics: Dapsone; Humans; Leprosy; Mycobacterium leprae; Recurrence; Risk Factors
PubMed: 35643395
DOI: 10.1016/j.jgar.2022.05.015