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Journal of Global Antimicrobial... Sep 2023The aim of the study was to update the classification of drugs used in multidrug-resistant tuberculosis (MDR-TB) regimens. Group A drugs (fluoroquinolones, bedaquiline... (Meta-Analysis)
Meta-Analysis Review
Evaluation of genetic mutations associated with phenotypic resistance to fluoroquinolones, bedaquiline, and linezolid in clinical Mycobacterium tuberculosis: A systematic review and meta-analysis.
OBJECTIVES
The aim of the study was to update the classification of drugs used in multidrug-resistant tuberculosis (MDR-TB) regimens. Group A drugs (fluoroquinolones, bedaquiline (BDQ), and linezolid (LZD)) are crucial drugs for the control of MDR-TB. Molecular drug resistance assays could facilitate the effective use of Group A drugs.
METHODS
We summarised the evidence implicating specific genetic mutations in resistance to Group A drugs. We searched PubMed, Embase, MEDLINE, and the Cochrane Library for studies published from the inception of each database until July 1, 2022. Using a random-effects model, we calculated the odds ratios and 95% confidence intervals as our measures of association.
RESULTS
A total of 5001 clinical isolates were included in 47 studies. Mutations in gyrA A90V, D94G, D94N, and D94Y were significantly associated with an increased risk of a levofloxacin (LFX)-resistant phenotype. In addition, mutations in gyrA G88C, A90V, D94G, D94H, D94N, and D94Y were significantly associated with an increased risk of a moxifloxacin (MFX)-resistant phenotype. In only one study, the majority of gene loci (n = 126, 90.65%) in BDQ-resistant isolates were observed to have unique mutations in atpE, Rv0678, mmpL5, pepQ, and Rv1979c. The most common mutations occurred at four sites in the rrl gene (g2061t, g2270c, g2270t, and g2814t) and at one site in rplC (C154R) in LZD-resistant isolates. Our meta-analysis demonstrated that there were no mutations associated with BDQ- or LZD-resistant phenotypes.
CONCLUSION
The mutations detected by rapid molecular assay were correlated with phenotypic resistance to LFX and MFX. The absence of mutation-phenotype associations for BDQ and LZD hindered the development of a rapid molecular assay.
Topics: Humans; Mycobacterium tuberculosis; Linezolid; Fluoroquinolones; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Levofloxacin; Phenotype
PubMed: 37172764
DOI: 10.1016/j.jgar.2023.05.001 -
American Journal of Infection Control Jul 2022To identify the prevalence and incidence of tuberculosis in health workers. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To identify the prevalence and incidence of tuberculosis in health workers.
METHOD
Systematic literature review, according to the protocol of the Joanna Briggs Institute and report following PRISMA guidelines. Primary studies containing data on the incidence or prevalence of active or latent tuberculosis infection in health workers were considered.
RESULTS
2,310 potentially relevant studies were identified in ten databases, of which 24 were included. The prevalence of latent tuberculosis varied between 0.1% and 62.0%, and the annual incidence rate varied from 1.4% to 11.4%. A meta-analysis combining data from the studies identified the prevalence as 28% (95% CI 21-36). Occupational risk factors are related to direct contact with patients having active tuberculosis, and more years of professional experience.
CONCLUSIONS
Evidences show that tuberculosis is an important occupational problem in health care; however, there are still gaps in information about the epidemiology of tuberculosis in health workers, mainly related to the risk factors.
Topics: Health Personnel; Humans; Incidence; Latent Tuberculosis; Prevalence; Risk Factors; Tuberculosis
PubMed: 35108578
DOI: 10.1016/j.ajic.2022.01.021 -
Journal of Clinical Tuberculosis and... Aug 2023Tuberculosis (TB) is still one of the leading causes of worldwide death, especially following the emergence of strains resistant to isoniazid (INH) and rifampicin (RIF)....
Tuberculosis (TB) is still one of the leading causes of worldwide death, especially following the emergence of strains resistant to isoniazid (INH) and rifampicin (RIF). This study aimed to systematically review published articles focusing on the prevalence of INH and/or RIF resistance-associated mutations of isolates in recent years. Literature databases were searched using appropriate keywords. The data of the included studies were extracted and used for a random-effects model -analysis. Of the initial 1442 studies, 29 were finally eligible to be included in the review. The overall resistance to INH and RIF was about 17.2% and 7.3%, respectively. There was no difference between the frequency of INH and RIF resistance using different phenotypic or genotypic methods. The INH and/or RIF resistance was higher in Asia. The S315T mutation in KatG (23.7 %), C-15 T in InhA (10.7 %), and S531L in RpoB (13.5 %) were the most prevalent mutations. Altogether, the results showed that due to S531L in RpoB, S315T in KatG, and C-15 T in InhA mutations INH- and RIF-resistant isolates were widely distributed. Thus, it would be diagnostically and epidemiologically beneficial to track these gene mutations among resistant isolates.
PubMed: 37389010
DOI: 10.1016/j.jctube.2023.100379 -
PloS One 2021Diagnosis of tuberculosis (TB) is still difficult. The purpose of our study was to evaluate the diagnostic accuracy of Mycobacterium tuberculosis cell-free DNA (cfDNA)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diagnosis of tuberculosis (TB) is still difficult. The purpose of our study was to evaluate the diagnostic accuracy of Mycobacterium tuberculosis cell-free DNA (cfDNA) for diagnosing of TB.
METHODS
We searched relevant databases for studies that used cfDNA to diagnose TB. We evaluated the accuracy of cfDNA compared with the composite reference standard (CRS) and culture. True positive, false positive, false negative, and true negative values for cfDNA were obtained first, then the estimated pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic odds ratio (DOR), and the area under the summary receiver operating characteristic (SROC) curve (AUC) of cfDNA for diagnosing TB were calculated with 95% confidence intervals (CIs). Heterogeneity was determined using the I2 statistic. When the heterogeneity was obvious, the source of heterogeneity was further discussed.
RESULTS
We included 14 independent studies comparing cfDNA with the CRS, and 4 studies compared with culture. The pooled sensitivity, specificity, PPV, NPV, DOR, and AUC of the SROC were 68%, 98%,99%, 62%, 83, and 0.97 as compared with the CRS, respectively. The pooled sensitivity, specificity, PPV, NPV, DOR, and AUC of the SROC were 48%, 91%, 92%, 60%, 5, and 0.88 as compared with culture, respectively. The heterogeneity between studies was significant.
CONCLUSIONS
The accuracy of cfDNA testing for TB diagnosis was good compared with CRS and culture. cfDNA can be used for rapid early diagnosis of TB.
Topics: Cell-Free Nucleic Acids; Humans; Mycobacterium tuberculosis; Sensitivity and Specificity; Tuberculosis
PubMed: 34161399
DOI: 10.1371/journal.pone.0253658 -
Clinical Infectious Diseases : An... Jun 2023We compared 6 new interferon-γ release assays (IGRAs; hereafter index tests: QFT-Plus, QFT-Plus CLIA, QIAreach, Wantai TB-IGRA, Standard E TB-Feron, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We compared 6 new interferon-γ release assays (IGRAs; hereafter index tests: QFT-Plus, QFT-Plus CLIA, QIAreach, Wantai TB-IGRA, Standard E TB-Feron, and T-SPOT.TB/T-Cell Select) with World Health Organization (WHO)-endorsed tests for tuberculosis infection (hereafter reference tests).
METHODS
Data sources (1 January 2007-18 August 2021) were Medline, Embase, Web of Science, Cochrane Database of Systematic Reviews, and manufacturers' data. Cross-sectional and cohort studies comparing the diagnostic performance of index and reference tests were selected. The primary outcomes of interest were the pooled differences in sensitivity and specificity between index and reference tests. The certainty of evidence (CoE) was summarized using the GRADE approach.
RESULTS
Eighty-seven studies were included (44 evaluated the QFT-Plus, 4 QFT-Plus CLIA, 3 QIAreach, 26 TB-IGRA, 10 TB-Feron [1 assessing the QFT-Plus], and 1 T-SPOT.TB/T-Cell Select). Compared to the QFT-GIT, QFT Plus's sensitivity was 0.1 percentage points lower (95% confidence interval [CI], -2.8 to 2.6; CoE: moderate), and its specificity 0.9 percentage points lower (95% CI, -1.0 to -.9; CoE: moderate). Compared to QFT-GIT, TB-IGRA's sensitivity was 3.0 percentage points higher (95% CI, -.2 to 6.2; CoE: very low), and its specificity 2.6 percentage points lower (95% CI, -4.2 to -1.0; CoE: low). Agreement between the QFT-Plus CLIA and QIAreach with QFT-Plus was excellent (pooled κ statistics of 0.86 [95% CI, .78 to .94; CoE: low]; and 0.96 [95% CI, .92 to 1.00; CoE: low], respectively). The pooled κ statistic comparing the TB-Feron and the QFT-Plus or QFT-GIT was 0.85 (95% CI, .79 to .92; CoE: low).
CONCLUSIONS
The QFT-Plus and the TB-IGRA have very similar sensitivity and specificity as WHO-approved IGRAs.
Topics: Humans; Interferon-gamma Release Tests; Cross-Sectional Studies; Tuberculosis; Latent Tuberculosis; Sensitivity and Specificity; Tuberculin Test; Mycobacterium tuberculosis
PubMed: 36688489
DOI: 10.1093/cid/ciad030 -
Salud Publica de Mexico 2014To compare drug resistance (DR) rates and genetic diversity of Mycobacterium tuberculosis strains from different states of Mexico. (Review)
Review
OBJECTIVE
To compare drug resistance (DR) rates and genetic diversity of Mycobacterium tuberculosis strains from different states of Mexico.
MATERIALS AND METHODS
A systematic review of English and Spanish-language articles using MEDLINE and Google Scholar. Search terms included Mycobacterium tuberculosis, Mexico, resistance, mutation and epidemiology.
RESULTS
Fifteen studies for phenotypic DR rates (n=2 694), twelve studies for genotypic DR (n=748) and eleven studies for genetic diversity (n=2 044) met our inclusion criteria. Mean DR and multidrug resistance (MDR) rates were 37.5% and 20.6%, respectively. The most frequent mutations were rpoB531 (53.1%), katG315 (50.6%), embB306 (32.1%), rpsL43 (14.6%) and pncA359 (16.7%) in DR strains. Novel mutations were found. Predominant shared types were SIT53 (T1, n=188, 3.9%), SIT119 (X1, n=125, 6.9%), SIT19 (EAI2-Manila, n=80, 6.3%) and SIT42 (LAM9, n=77, 3.0%). SIT1 Beijing genotype has been reported in six states from Mexico.
CONCLUSIONS
DR and MDR rates continue to increase. Genetic diversity of M. tuberculosis strains in Mexico is high. Reports of Beijing strains are increasing.
Topics: Drug Resistance, Bacterial; Humans; Mexico; Molecular Epidemiology; Mycobacterium tuberculosis
PubMed: 24912522
DOI: 10.21149/spm.v56i1.7324 -
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 -
BMJ (Clinical Research Ed.) Aug 2014To determine whether BCG vaccination protects against Mycobacterium tuberculosis infection as assessed by interferon γ release assays (IGRA) in children. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To determine whether BCG vaccination protects against Mycobacterium tuberculosis infection as assessed by interferon γ release assays (IGRA) in children.
DESIGN
Systematic review and meta-analysis. Searches of electronic databases 1950 to November 2013, checking of reference lists, hand searching of journals, and contact with experts.
SETTING
Community congregate settings and households.
INCLUSION CRITERIA
Vaccinated and unvaccinated children aged under 16 with known recent exposure to patients with pulmonary tuberculosis. Children were screened for infection with M tuberculosis with interferon γ release assays.
DATA EXTRACTION
Study results relating to diagnostic accuracy were extracted and risk estimates were combined with random effects meta-analysis.
RESULTS
The primary analysis included 14 studies and 3855 participants. The estimated overall risk ratio was 0.81 (95% confidence interval 0.71 to 0.92), indicating a protective efficacy of 19% against infection among vaccinated children after exposure compared with unvaccinated children. The observed protection was similar when estimated with the two types of interferon γ release assays (ELISpot or QuantiFERON). Restriction of the analysis to the six studies (n=1745) with information on progression to active tuberculosis at the time of screening showed protection against infection of 27% (risk ratio 0.73, 0.61 to 0.87) compared with 71% (0.29, 0.15 to 0.58) against active tuberculosis. Among those infected, protection against progression to disease was 58% (0.42, 0.23 to 0.77).
CONCLUSIONS
BCG protects against M tuberculosis infection as well as progression from infection to disease.Trial registration PROSPERO registration No CRD42011001698 (www.crd.york.ac.uk/prospero/).
Topics: Adolescent; BCG Vaccine; Child; Child, Preschool; Humans; Infant; Interferon-gamma; Interferon-gamma Release Tests; Mycobacterium tuberculosis; Tuberculosis
PubMed: 25097193
DOI: 10.1136/bmj.g4643 -
Systematic Reviews Oct 2021Rapid and accurate diagnosis of paediatric tuberculosis (TB) is key to manage the disease and to control and prevent its transmission. Collection of quality sputum... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rapid and accurate diagnosis of paediatric tuberculosis (TB) is key to manage the disease and to control and prevent its transmission. Collection of quality sputum samples without invasion methods from paediatrics (age < 16 years) with presumptive pulmonary tuberculosis (PTB) remains a challenge. Thus, the aim of this meta-analysis was to assess the overall accuracy of a real-time polymerase chain reaction (RT-PCR)-based assay, for routine diagnosis of MTB in different samples from paediatrics with active pulmonary and extra-pulmonary tuberculosis using mycobacterial culture as the gold standard in clinical microbiology laboratories.
METHODS
We conducted a systematic review and meta-analysis to examine the diagnostic test accuracy of RT-PCR based assay for the detection of MTB in paediatric clinical samples. A systematic literature search was performed for publications in any language. MEDLINE via PubMed, EMBASE, and Web of Science were among 9 bibliographic databases searched from August 2019 until November 2020. Bivariate random-effects model of meta-analysis were performed to generate pooled summary estimates (95% CIs) for overall accuracy of RT-PCR based assay compared to mycobacterial culture as the reference standard.
RESULTS
Of the 1592 candidate studies, twenty-one eligible studies met our inclusion criteria. In total, the review and meta-analysis included 5536 (3209 PTB and 2327 EPTB). Summary estimates for pulmonary TB (11 studies) were as follows: sensitivity 56 (95% CI 51-62), specificity 97 (95% CI 96-98) and summary estimates for extra-pulmonary TB (10 studies) were as follows: sensitivity 87 (95% CI 82-91)) specificity 100 (95% CI 99-100). There was significant heterogeneity in sensitivity and specificity among the enrolled studies (p < 0.001).
CONCLUSIONS
Our results suggested that the RT-PCR based assay could be a useful test for the diagnosis of paediatrics TB with high sensitivity and specificity in low-income/high-burden and upper medium income/low-burden settings. From the study, RT-PCR assay demonstrated a high degree of sensitivity for extra-pulmonary TB and good sensitivity for pulmonary TB which is an important factor in achieving effective global control and for patient management in terms of initiating early and appropriate anti-tubercular therapy.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42018104052.
Topics: Adolescent; Child; Humans; Mycobacterium tuberculosis; Pediatrics; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Pulmonary
PubMed: 34706779
DOI: 10.1186/s13643-021-01836-w -
The Journal of Infection Dec 2019The globally distributed "Beijing" lineage of Mycobacterium tuberculosis has been associated with outbreaks worldwide. Laboratory based studies have suggested that... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The globally distributed "Beijing" lineage of Mycobacterium tuberculosis has been associated with outbreaks worldwide. Laboratory based studies have suggested that Beijing lineage may have increased fitness; however, it has not been established whether these differences are of epidemiological significance with regards to transmission. Therefore, we undertook a systematic review of epidemiological studies of tuberculosis clustering to compare the transmission dynamics of Beijing lineages versus the non-Beijing lineages.
METHODS
We systematically searched Embase and MEDLINE before 31st December 2018, for studies which provided information on the transmission dynamics of the different M. tuberculosis lineages. We included articles that conducted population-based cross-sectional or longitudinal molecular epidemiological studies reporting information about extent of transmission of different lineages. The protocol for this systematic review was prospectively registered with PROSPERO (CDR42018088579).
RESULTS
Of 2855 records identified by the search, 46 were included in the review, containing 42,700 patients from 27 countries. Beijing lineage was the most prevalent and highly clustered strain in 72.4% of the studies and had a higher likelihood of transmission than non-Beijing lineages (OR 1·81 [95% 1·28-2·57], I = 94·0%, τ = 0·59, p < 0·01).
CONCLUSIONS
Despite considerable heterogeneity across epidemiological contexts, Beijing lineage appears to be more transmissible than other lineages.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Cluster Analysis; Disease Transmission, Infectious; Female; Global Health; Humans; Infant; Infant, Newborn; Male; Middle Aged; Mycobacterium tuberculosis; Prevalence; Tuberculosis; Young Adult
PubMed: 31585190
DOI: 10.1016/j.jinf.2019.09.016