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BMC Infectious Diseases 2014Previous meta-analyses regarding the performance of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting results, probably... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis on the utility of Interferon-gamma release assays for the diagnosis of Mycobacterium tuberculosis infection in children: a 2013 update.
BACKGROUND
Previous meta-analyses regarding the performance of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting results, probably due to different inclusion/exclusion criteria.
METHODS
We systematically searched PubMed, EMBASE and Cochrane databases and calculated pooled estimates of sensitivities and specificities of QuantiFERON-TB Gold In Tube (QFT-G-IT), T-SPOT.TB, and tuberculin skin test (TST). Several sub-analysis were performed: stratification by background (low income vs. high income countries); including only microbiological confirmed TB cases; including only studies performing a simultaneous three-way comparison of the three tests, and including immunocompromised children.
RESULTS
Overall, 31 studies (6183 children) for QFT-G-IT, 14 studies (2518 children) for T-SPOT.TB and 34 studies (6439 children) for TST were included in the analyses. In high income countries QFT-G-IT sensitivity was 0.79 (95%IC: 0.75-0.82) considering all the studies, 0.78 (95%CI:0.70-0.84) including only studies performing a simultaneous three-way comparison and 0.86 (95%IC 0.81-0.90) considering only microbiologically confirmed studies. In the same analyses T-SPOT.TB sensitivity was 0.67 (95%IC 0.62-0.73); 0.76 (95%CI: 0.68 to 0.83); and 0.79 (95%IC 0.69-0.87), respectively. In low income countries QFT-G-IT pooled sensitivity was significantly lower: 0.57 (95%IC:0.52-0.61), considering all the studies, and 0.66 (95%IC 0.55-0.76) considering only microbiologically confirmed cases; while T-SPOT.TB sensitivity was 0.61 (95%IC 0.57-0.65) overall, but reached 0.80 (95%IC 0.73-0.86) in microbiologically confirmed cases. In microbiologically confirmed cases TST sensitivity was similar: 0.86 (95%IC 0.79-0.91) in high income countries, and 0.74 (95%IC 0.68-0.80) in low income countries. Higher IGRAs specificity with respect to TST was observed in high income countries (97-98% vs. 92%) but not in low income countries (85-93% vs. 90%).
CONCLUSIONS
Both IGRAs showed no better performance than TST in low income countries.
Topics: Child; Developed Countries; Developing Countries; HIV Infections; Humans; Immunocompromised Host; Interferon-gamma Release Tests; Mycobacterium tuberculosis; Sensitivity and Specificity; Tuberculin Test; Tuberculosis
PubMed: 24564486
DOI: 10.1186/1471-2334-14-S1-S6 -
European Respiratory Review : An... Jun 2023A substantial proportion of tuberculosis patients remain with pulmonary symptoms and reduced physical capacity despite successful treatment. We performed a systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A substantial proportion of tuberculosis patients remain with pulmonary symptoms and reduced physical capacity despite successful treatment. We performed a systematic review to analyse the burden of post-tuberculosis lung impairment measured by lung function testing.
METHODS
We searched the PubMed database for articles published between database inception and November 2020 and performed meta-analyses to estimate the prevalence, type and severity of lung impairment among drug-susceptible and multidrug-resistant tuberculosis survivors. Methodological quality of included studies was assessed using the Newcastle-Ottawa scale.
RESULTS
54 articles were included in this review. For subjects with former drug-susceptible tuberculosis, the combined estimated mean was 76.6% (95% CI 71.6-81.6) of predicted for forced expiratory volume in 1 s (FEV) and 81.8% (95% CI 77.4-86.2) for forced vital capacity (FVC). In former patients with multidrug-resistant tuberculosis, it was 65.9% (95% CI 57.1-74.7) for FEV and 76.0% (95% CI 66.3-85.8) for FVC, respectively. The analysis of impairment types in former patients with drug-susceptible and multidrug-resistant tuberculosis showed that 22.0% 19.0% had obstructive, 23.0% 22.0% restrictive and 15.0% 43.0% had mixed impairment type, respectively. In the majority of studies, at least 10-15% of tuberculosis survivors had severe lung impairment.
CONCLUSIONS
This systematic review showed long-term abnormal spirometry results in a significant proportion of tuberculosis survivors.
Topics: Humans; Lung; Spirometry; Vital Capacity; Forced Expiratory Volume; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 37076175
DOI: 10.1183/16000617.0221-2022 -
The Journal of Rheumatology. Supplement May 2014In this systematic review we evaluate the role of chest radiography (CXR) in the diagnostic flow chart for tuberculosis (TB) infection, focusing on latent TB infection... (Review)
Review
In this systematic review we evaluate the role of chest radiography (CXR) in the diagnostic flow chart for tuberculosis (TB) infection, focusing on latent TB infection (LTBI) in patients requiring medical treatment with biological drugs. In recent findings, patients scheduled for immunomodulatory therapy with biologic drugs are a group at risk of TB reactivation and, in such patients, detection of LTBI is of great importance. CXR for diagnosis of pulmonary TB has good sensitivity, but poor specificity. Radiographic diagnosis of active disease can only be reliably made on the basis of temporal evolution of pulmonary lesions. In vivo tuberculin skin test and ex vivo interferon-γ release assays are designed to identify development of an adaptive immune response, but not necessarily LTBI. Computed tomography (CT) is able to distinguish active from inactive disease. CT is considered a complementary imaging modality to CXR in the screening procedure to detect past and LTBI infection in specific subgroups of patients who have increased risk for TB reactivation, including those scheduled for medical treatment with biological drugs.
Topics: Humans; Interferon-gamma Release Tests; Latent Tuberculosis; Radiography, Thoracic; Sensitivity and Specificity; Tuberculin Test; Tuberculosis
PubMed: 24788998
DOI: 10.3899/jrheum.140100 -
The Journal of Infection Sep 2023Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the 2006 extensively drug-resistant tuberculosis definitions and old treatment regimens are being replaced, we aimed to estimate the proportion of extensively drug-resistant tuberculosis patients globally who achieved successful treatment outcomes.
METHODS
We conducted a systematic review of PubMed/MEDLINE, Scopus, Web of Science, and Embase from January 1, 2005, through April 3, 2023. Included studies reported WHO treatment outcomes, or adaptions hereof, for pre-extensively and/or extensively drug-resistant tuberculosis patients according to the 2006 WHO definition. Eligible studies included cohorts of at least 10 adults (aged>18 years) that were not pregnant. Using a random-effects model, we calculated pooled proportions of treatment outcomes and performed sensitivity and subgroup analyses. PROSPERO registration number: CRD42022340961.
RESULTS
Among 5056 studies reviewed, we identified 94 studies from 26 countries, involving 10,223 extensively drug-resistant tuberculosis patients. The pooled proportion of successful treatment outcomes was 44.2% (95%CI: 38.3-50.3). Sensitivity analyses consistently produced similar estimates. A slight improvement in treatment outcomes was observed after 2013. Furthermore, 25 studies reported outcomes for 3564 individuals with pre-extensively drug-resistant tuberculosis, of which 63.3% achieved successful treatment (95%CI: 43.1-72.5).
CONCLUSION
Globally, the success rate of extensively drug-resistant tuberculosis treatment is 44.2%, far below the WHO's target rate of 75%. These results may serve as a reference for future studies assessing extensively drug-resistant tuberculosis treatment outcomes under the 2021 definition treated with better treatment regimens available. Comprehensive surveillance data of extensively drug-resistant tuberculosis outcomes from the whole world are desirable to monitor treatment progress.
Topics: Humans; Adult; Pregnancy; Female; Extensively Drug-Resistant Tuberculosis; Tuberculosis, Pulmonary; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Antitubercular Agents
PubMed: 37356629
DOI: 10.1016/j.jinf.2023.06.014 -
The Lancet. Microbe Oct 2023Pulmonary tuberculosis due to Mycobacterium tuberculosis can be challenging to diagnose when sputum samples cannot be obtained, which is especially problematic in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pulmonary tuberculosis due to Mycobacterium tuberculosis can be challenging to diagnose when sputum samples cannot be obtained, which is especially problematic in children and older people. We systematically appraised the performance characteristics and diagnostic accuracy of upper respiratory tract sampling for diagnosing active pulmonary tuberculosis.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, Cinahl, Web of Science, Global Health, and Global Health Archive databases for studies published between database inception and Dec 6, 2022 that reported on the accuracy of upper respiratory tract sampling for tuberculosis diagnosis compared with microbiological testing of sputum or gastric aspirate reference standard. We included studies that evaluated the accuracy of upper respiratory tract sampling (laryngeal swabs, nasopharyngeal aspirate, oral swabs, saliva, mouth wash, nasal swabs, plaque samples, and nasopharyngeal swabs) to be tested for microbiological diagnosis of tuberculous (by culture and nucleic acid amplification tests) compared with a reference standard using either sputum or gastric lavage for a microbiological test. We included cohort, case-control, cross-sectional, and randomised controlled studies that recruited participants from any community or clinical setting. We excluded post-mortem studies. We used a random-effects meta-analysis with a bivariate hierarchical model to estimate pooled sensitivity, specificity, and diagnostics odds ratio (DOR; odds of a positive test with disease relative to without), stratified by sampling method. We assessed bias using QUADAS-2 criteria. This study is registered with PROSPERO (CRD42021262392).
FINDINGS
We screened 10 159 titles for inclusion, reviewed 274 full texts, and included 71, comprising 119 test comparisons published between May 13, 1933, and Dec 19, 2022, in the systematic review (53 in the meta-analysis). For laryngeal swabs, pooled sensitivity was 57·8% (95% CI 50·5-65·0), specificity was 93·8% (88·4-96·8), and DOR was 20·7 (11·1-38·8). Nasopharyngeal aspirate sensitivity was 65·2% (52·0-76·4), specificity was 97·9% (96·0-99·0), and DOR was 91·0 (37·8-218·8). Oral swabs sensitivity was 56·7% (44·3-68·2), specificity was 91·3% (CI 81·0-96·3), and DOR was 13·8 (5·6-34·0). Substantial heterogeneity in diagnostic accuracy was found, probably due to differences in reference and index standards.
INTERPRETATION
Upper respiratory tract sampling holds promise to expand access to tuberculosis diagnosis. Exploring historical methods using modern microbiological techniques might further increase options for alternative sample types. Prospective studies are needed to optimise accuracy and utility of sampling methods in clinical practice.
FUNDING
UK Medical Research Council, Wellcome, and UK Foreign, Commonwealth and Development Office.
Topics: Child; Humans; Aged; Mycobacterium tuberculosis; Cross-Sectional Studies; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Pulmonary; Respiratory System
PubMed: 37714173
DOI: 10.1016/S2666-5247(23)00190-8 -
Tropical Medicine & International... Oct 2022To summarise latent tuberculosis infection (LTBI) management strategies among household contacts of bacteriologically confirmed pulmonary tuberculosis (TB) patients in... (Meta-Analysis)
Meta-Analysis Review
Strategies to detect and manage latent tuberculosis infection among household contacts of pulmonary TB patients in high TB burden countries - a systematic review and meta-analysis.
OBJECTIVE
To summarise latent tuberculosis infection (LTBI) management strategies among household contacts of bacteriologically confirmed pulmonary tuberculosis (TB) patients in high-TB burden countries.
METHODS
PubMed/MEDLINE (NCBI) and Scopus were searched (January 2006 to December 2021) for studies reporting primary data on LTBI management. Study selection, data management and data synthesis were protocol-driven (PROSPERO-CRD42021208715). Primary outcomes were the proportions of LTBI, initiating and completing tuberculosis preventive treatment (TPT). Reported factors influencing the LTBI care cascade were qualitatively synthesised.
RESULTS
From 3694 unique records retrieved, 58 studies from 23 countries were included. Most identified contacts were screened (median 99%, interquartile range [IQR] 82%-100%; 46 studies). Random-effects meta-analysis yielded pooled proportions for: LTBI 41% (95% confidence interval [CI] 33%-49%; 21,566 tested contacts); TPT initiation 91% (95% CI 79%-97%; 129,573 eligible contacts, 34 studies); TPT completion 65% (95% CI 54%-74%; 108,679 TPT-initiated contacts, 28 studies). Heterogeneity was significant (I ≥ 95%-100%) and could not be explained in subgroup analyses. Median proportions (IQR) were: LTBI 44% (28%-59%); TPT initiation 86% (60%-100%); TPT completion 68% (44%-82%). Nine broad themes related to diagnostic testing, health system structure and functions, risk perception, documentation and adherence were considered likely to influence the LTBI care cascade.
CONCLUSION
The proportions of household contacts screened, detected with LTBI and initiated on TPT, though variable was high, but the proportions completing TPT were lower indicating current strategies used for LTBI management in high TB burden countries are not sufficient.
Topics: Humans; Latent Tuberculosis; Tuberculosis, Pulmonary
PubMed: 35927930
DOI: 10.1111/tmi.13808 -
PloS One 2020Tuberculosis remains a leading cause of death worldwide. Transmission is the dominant mechanism sustaining the multidrug-resistant tuberculosis epidemic. Tuberculosis...
Barriers and facilitators of tuberculosis infection prevention and control in low- and middle-income countries from the perspective of healthcare workers: A systematic review.
Tuberculosis remains a leading cause of death worldwide. Transmission is the dominant mechanism sustaining the multidrug-resistant tuberculosis epidemic. Tuberculosis infection prevention and control (TBIPC) guidelines for healthcare facilities are poorly implemented. This systematic review aimed to explore the barriers and facilitators of implementation of TBIPC guidelines in low- and middle-income countries from the perspective of healthcare workers. Two separate reviewers carried out an electronic database search to select qualitative and quantitative studies exploring healthcare workers attitudes towards TBIPC. Eligible studies underwent thematic synthesis. Derived themes were further organised into a macro-, meso- and micro-level framework, which allows us to analyse barriers at different levels of the healthcare system. We found that most studies focused on assessing implementation within facilities in accordance with the hierarchy of TBIPC measures-administrative, environmental and respiratory protection controls. TBIPC implementation was over-estimated by self-report compared with what researchers observed within facilities, indicating a knowledge-action gap. Macro-level barriers included the lack of coordination of integrated HIV/tuberculosis care, in the context of an expanding antiretroviral therapy programme and hence increasing opportunity for nosocomial acquisition of tuberculosis; a lack of funding; and ineffective occupational health policies, such as poor systems for screening for tuberculosis amongst healthcare workers. Meso-level barriers included little staff training to implement programmes, and managers not understanding policy sufficiently to translate it into an IPC programme. Most studies reported micro-level barriers including the impact of stigma, work culture, lack of perception of risk, poor supply and use of respirators and difficulty sensitising patients to the need for IPC. Existing literature on healthcare workers' attitudes to TBIPC focusses on collecting data about poor implementation at facility level. In order to bridge the knowledge-action gap, we need to understand how best to implement policy, taking account of the context.
Topics: Health Facilities; Health Knowledge, Attitudes, Practice; Health Personnel; Humans; Mycobacterium tuberculosis; Patient Acceptance of Health Care; Patient Compliance; Tuberculosis
PubMed: 33085717
DOI: 10.1371/journal.pone.0241039 -
Journal of Paediatrics and Child Health Apr 2020Refugees are at increased risk of tuberculosis infection due to time spent in crowded camps, decreased nutrition and originating from countries whose own tuberculosis...
AIM
Refugees are at increased risk of tuberculosis infection due to time spent in crowded camps, decreased nutrition and originating from countries whose own tuberculosis control systems may have been disturbed. In Australia, tuberculosis is screened for in for all refugees aged 11-34 years old and in those aged 2-10 years arriving from high-incidence countries. Our aims were to determine if refugee children aged under 2 years of age should also be screened.
METHODS
A systematic literature review and meta-regression was carried out on studies in refugee children under 18 years old, involving screening for tuberculosis (active or latent tuberculosis infection (LTBI)). Studies were extracted from the last 10 years from a range of bibliographic databases using the search terms 'tuberculosis', 'children', 'screening' and 'refugee', which tested for tuberculosis using the tuberculin skin test (TST) or QuantiFERON-Gold (Interferon Gamma Release Assay (IGRA)).
RESULTS
Of the 15 included studies, prevalence of LTBI in < 2-year-olds was 5% using IGRA and 15% using TST (P < 0.05). Prevalence increased with age (odds ratio 1.12; 95% confidence interval: 1.06-1.17) cumulatively and decreased where IGRA was used for screening compared to TST (odds ratio 0.38; 95% confidence interval: 0.25-0.58). Prevalence of LTBI did not differ between general versus clinic refugee cohorts.
CONCLUSIONS
Refugees are a particularly vulnerable group in their susceptibility to tuberculosis, and LTBI management is a critical part of tuberculosis disease control due to the lifetime risk of developing active tuberculosis. A prevalence of 5-15% for LTBI in the under 2 years age group would support them being included in screening programmes.
Topics: Adolescent; Adult; Australia; Child; Child, Preschool; Humans; Latent Tuberculosis; Mass Screening; Refugees; Regression Analysis; Tuberculin Test; Tuberculosis; Young Adult
PubMed: 31883282
DOI: 10.1111/jpc.14701 -
PloS One 2012Despite the widespread use of interferon-γ release assays (IGRAs), their role in diagnosing tuberculosis and targeting preventive therapy in HIV-infected patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite the widespread use of interferon-γ release assays (IGRAs), their role in diagnosing tuberculosis and targeting preventive therapy in HIV-infected patients remains unclear. We conducted a comprehensive systematic review to contribute to the evidence-based practice in HIV-infected people.
METHODOLOGY/PRINCIPAL FINDINGS
We searched MEDLINE, Cochrane, and Biomedicine databases to identify articles published between January 2005 and July 2011 that assessed QuantiFERON®-TB Gold In-Tube (QFT-GIT) and T-SPOT®.TB (T-SPOT.TB) in HIV-infected adults. We assessed their accuracy for the diagnosis of tuberculosis and incident active tuberculosis, and the proportion of indeterminate results. The search identified 38 evaluable studies covering a total of 6514 HIV-infected participants. The pooled sensitivity and specificity for tuberculosis were 61% and 72% for QFT-GIT, and 65% and 70% for T-SPOT.TB. The cumulative incidence of subsequent active tuberculosis was 8.3% for QFT-GIT and 10% for T-SPOT.TB in patients tested positive (one study each), and 0% for QFT-GIT (two studies) and T-SPOT.TB (one study) respectively in those tested negative. Pooled indeterminate rates were 8.2% for QFT-GIT and 5.9% for T-SPOT.TB. Rates were higher in high burden settings (12.0% for QFT-GIT and 7.7% for T-SPOT.TB) than in low-intermediate burden settings (3.9% for QFT-GIT and 4.3% for T-SPOT.TB). They were also higher in patients with CD4(+) T-cell count <200 (11.6% for QFT-GIT and 11.4% for T-SPOT.TB) than in those with CD4(+) T-cell count ≥ 200 (3.1% for QFT-GIT and 7.9% for T-SPOT.TB).
CONCLUSIONS/SIGNIFICANCE
IGRAs have suboptimal accuracy for confirming or ruling out active tuberculosis disease in HIV-infected adults. While their predictive value for incident active tuberculosis is modest, a negative QFT-GIT implies a very low short- to medium-term risk. Identifying the factors associated with indeterminate results will help to optimize the use of IGRAs in clinical practice, particularly in resource-limited countries with a high prevalence of HIV-coinfection.
Topics: Adult; HIV Infections; Humans; Interferon-gamma Release Tests; Quality Control; Sensitivity and Specificity; Tuberculosis
PubMed: 22403663
DOI: 10.1371/journal.pone.0032482 -
The European Respiratory Journal Jan 2013Investigation of contacts of patients with tuberculosis (TB) is a priority for TB control in high-income countries, and is increasingly being considered in... (Meta-Analysis)
Meta-Analysis Review
Investigation of contacts of patients with tuberculosis (TB) is a priority for TB control in high-income countries, and is increasingly being considered in resource-limited settings. This review was commissioned for a World Health Organization Expert Panel to develop global contact investigation guidelines. We performed a systematic review and meta-analysis of all studies reporting the prevalence of TB and latent TB infection, and the annual incidence of TB among contacts of patients with TB. After screening 9,555 titles, we included 203 published studies. In 95 studies from low- and middle-income settings, the prevalence of active TB in all contacts was 3.1% (95% CI 2.2-4.4%, I(2)=99.4%), microbiologically proven TB was 1.2% (95% CI 0.9-1.8%, I(2)=95.9%), and latent TB infection was 51.5% (95% CI 47.1-55.8%, I(2)=98.9%). The prevalence of TB among household contacts was 3.1% (95% CI 2.1-4.5%, I(2)=98.8%) and among contacts of patients with multidrug-resistant or extensively drug-resistant TB was 3.4% (95% CI 0.8-12.6%, I(2)=95.7%). Incidence was greatest in the first year after exposure. In 108 studies from high-income settings, the prevalence of TB among contacts was 1.4% (95% CI 1.1-1.8%, I(2)=98.7%), and the prevalence of latent infection was 28.1% (95% CI 24.2-32.4%, I(2)=99.5%). There was substantial heterogeneity among published studies. Contacts of TB patients are a high-risk group for developing TB, particularly within the first year. Children <5 yrs of age and people living with HIV are particularly at risk. Policy recommendations must consider evidence of the cost-effectiveness of various contact tracing strategies, and also incorporate complementary strategies to enhance case finding.
Topics: Contact Tracing; Humans; Tuberculosis, Pulmonary
PubMed: 22936710
DOI: 10.1183/09031936.00070812