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Frontiers in Public Health 2023Worldwide, COVID-19 pandemic lead to a large fall in the number of newly reported TB cases. In sub-Saharan Africa, microbiological diagnosis of TB is generally based on... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Worldwide, COVID-19 pandemic lead to a large fall in the number of newly reported TB cases. In sub-Saharan Africa, microbiological diagnosis of TB is generally based on smear microscopy and Xpert MTB/RIF on sputum samples, but good quality sputum samples are often difficult to obtain, leading clinicians to rely on more invasive procedures for diagnosis. Aim of this study was to investigate pooled sensitivity and specificity of Xpert MTB/RIF on stool samples compared to respiratory microbiological reference standards in African countries.
METHODS
Four investigators independently searched PubMed, SCOPUS, and Web of Science until 12th October 2022, then screened titles and abstracts of all potentially eligible articles. The authors applied the eligibility criteria, considered the full texts. All the studies reported the data regarding true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Risk of bias and applicability concerns were assessed with the Quadas-2 tool.
RESULTS
overall, among 130 papers initially screened, we evaluated 47 works, finally including 13 papers for a total of 2,352 participants, mainly children. The mean percentage of females was 49.6%, whilst the mean percentage of patients reporting HIV was 27.7%. Pooled sensitivity for Xpert MTB/RIF assay for detecting pulmonary tuberculosis was 68.2% (95%CI: 61.1-74.7%) even if characterized by a high heterogeneity (I=53.7%). Specificity was almost 100% (99%, 95%CI: 97-100%; I = 45.7%). When divided for reference standard, in the six studies using sputum and nasogastric aspirate the accuracy was optimal (AUC = 0.99, SE = 0.02), whilst in the studies using only sputum for tuberculosis detection the AUC was 0.85 (with a SE = 0.16). The most common source of bias was exclusion of enrolled patients in the analysis.
CONCLUSIONS
Our study confirms that, in Africa, stool Xpert MTB/RIF may be a useful rule-in test for children above and below 5 years of age under evaluation for pulmonary tuberculosis. Sensitivity increased substantially when using both sputum and nasogastric aspirate as reference samples.
Topics: Child; Female; Humans; Mycobacterium tuberculosis; Sputum; Pandemics; COVID-19; Tuberculosis, Pulmonary; Africa South of the Sahara; COVID-19 Testing
PubMed: 37293615
DOI: 10.3389/fpubh.2023.1117709 -
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 -
BMC Infectious Diseases May 2023Until now, the performance of interferon-γ release assay (IGRA) and Mantoux tests remains unclear in infant tuberculous meningitis (TBM). Therefore, a systematic review...
AIM
Until now, the performance of interferon-γ release assay (IGRA) and Mantoux tests remains unclear in infant tuberculous meningitis (TBM). Therefore, a systematic review is performed to evaluate the sensitivity of IGRA and Mantoux tests for the diagnosis of infant TBM in low and intermediate tuberculosis (TB) burden countries, while following PRISMA.
METHODS
Several databases, including PubMed, EBSCO, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials, were searched. Articles describing the results of IGRA or Mantoux tests among infant TBM were included for analysis. Data, such as age, sex, Mantoux test or IGRA, and cerebrospinal fluid (CSF) microbiological examinations (such as acid-fast bacilli (AFB) smear, TB PCR, and TB culture), were extracted from each study.
RESULTS
A total of 31 articles were enrolled for further analysis, including 48 cases. The mean age was 9.4 ± 5.8 months and boys accounted for 57.1% of infants (24/42). Mantoux test was positive in 57.4% (27/47) of tested infants and IGRA was positive in 77.8% (7/9) of infants. In addition, among the infants with confirmed TB, 18 (52.9%, 18/34) of them have positive Mantoux responses and 7 (20.0%, 7/35) have positive IGRA results.
CONCLUSIONS
In low or intermediate TB burden countries, the Mantoux test has a poor performance for diagnosing TBM among infants, and IGRAs appear to have a moderate sensitivity for the diagnosis of infant TBM.
Topics: Humans; Infant; Male; Interferon-gamma; Interferon-gamma Release Tests; Mycobacterium tuberculosis; Sensitivity and Specificity; Tuberculin Test; Tuberculosis, Meningeal; Female
PubMed: 37254061
DOI: 10.1186/s12879-023-08327-4 -
Journal of Chemotherapy (Florence,... Nov 2023Pyrazinamide (PZA) is an essential first-line tuberculosis drug for its unique mechanism of action active against multidrug-resistant-TB (MDR-TB). Thus, the aim of... (Meta-Analysis)
Meta-Analysis Review
Pyrazinamide (PZA) is an essential first-line tuberculosis drug for its unique mechanism of action active against multidrug-resistant-TB (MDR-TB). Thus, the aim of updated meta-analysis was to estimate the PZA weighted pooled resistance (WPR) rate in M. tuberculosis isolates based on publication date and WHO regions. We systematically searched the related reports in PubMed, Scopus, and Embase (from January 2015 to July 2022). Statistical analyses were performed using STATA software. The 115 final reports in the analysis investigated phenotypic PZA resistance data. The WPR of PZA was 57% (95% CI 48-65%) in MDR-TB cases. According to the WHO regions, the higher WPRs of PZA were reported in the Western Pacific (32%; 95% CI 18-46%), South East Asian region (37%; 95% CI 31-43%), and the Eastern Mediterranean (78%; 95% CI 54-95%) among any-TB patients, high risk of MDR-TB patients, and MDR-TB patients, respectively. A negligible increase in the rate of PZA resistance were showed in MDR-TB cases (55% to 58%). The rate of PZA resistance has been rising in recent years among MDR-TB cases, underlines the essential for both standard and novel drug regimens development.
Topics: Humans; Pyrazinamide; Mycobacterium tuberculosis; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Drug Resistance, Multiple, Bacterial; Amidohydrolases; Mutation; Microbial Sensitivity Tests; Tuberculosis
PubMed: 37211822
DOI: 10.1080/1120009X.2023.2214473 -
The Lancet. Global Health Jun 2023Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sputum is the most widely used sample to diagnose active tuberculosis, but many people living with HIV are unable to produce sputum. Urine, in contrast, is readily available. We hypothesised that sample availability influences the diagnostic yield of various tuberculosis tests.
METHODS
In this systematic review and meta-analysis of individual participant data, we compared the diagnostic yield of point-of-care urine-based lipoarabinomannan tests with that of sputum-based nucleic acid amplification tests (NAATs) and sputum smear microscopy (SSM). We used microbiologically confirmed tuberculosis based on positive culture or NAAT from any body site as the denominator and accounted for sample provision. We searched PubMed, Web of Science, Embase, African Journals Online, and clinicaltrials.gov from database inception to Feb 24, 2022 for randomised controlled trials, cross-sectional studies, and cohort studies that assessed urine lipoarabinomannan point-of-care tests and sputum NAATs for active tuberculosis detection in participants irrespective of tuberculosis symptoms, HIV status, CD4 cell count, or study setting. We excluded studies in which recruitment was not consecutive, systematic, or random; provision of sputum or urine was an inclusion criterion; less than 30 participants were diagnosed with tuberculosis; early research assays without clearly defined cutoffs were tested; and humans were not studied. We extracted study-level data, and authors of eligible studies were invited to contribute deidentified individual participant data. The main outcomes were the tuberculosis diagnostic yields of urine lipoarabinomannan tests, sputum NAATs, and SSM. Diagnostic yields were predicted using Bayesian random-effects and mixed-effects meta-analyses. This study is registered with PROSPERO, CRD42021230337.
FINDINGS
We identified 844 records, from which 20 datasets and 10 202 participants (4561 [45%] male participants and 5641 [55%] female participants) were included in the meta-analysis. All studies assessed sputum Xpert (MTB/RIF or Ultra, Cepheid, Sunnyvale, CA, USA) and urine Alere Determine TB LAM (AlereLAM, Abbott, Chicago, IL, USA) in people living with HIV aged 15 years or older. Nearly all (9957 [98%] of 10 202) participants provided urine, and 82% (8360 of 10 202) provided sputum within 2 days. In studies that enrolled unselected inpatients irrespective of tuberculosis symptoms, only 54% (1084 of 1993) of participants provided sputum, whereas 99% (1966 of 1993) provided urine. Diagnostic yield was 41% (95% credible interval [CrI] 15-66) for AlereLAM, 61% (95% Crl 25-88) for Xpert, and 32% (95% Crl 10-55) for SSM. Heterogeneity existed across studies in the diagnostic yield, influenced by CD4 cell count, tuberculosis symptoms, and clinical setting. In predefined subgroup analyses, all tests had higher yields in symptomatic participants, and AlereLAM yield was higher in those with low CD4 counts and inpatients. AlereLAM and Xpert yields were similar among inpatients in studies enrolling unselected participants who were not assessed for tuberculosis symptoms (51% vs 47%). AlereLAM and Xpert together had a yield of 71% in unselected inpatients, supporting the implementation of combined testing strategies.
INTERPRETATION
AlereLAM, with its rapid turnaround time and simplicity, should be prioritised to inform tuberculosis therapy among inpatients who are HIV-positive, regardless of symptoms or CD4 cell count. The yield of sputum-based tuberculosis tests is undermined by people living with HIV who cannot produce sputum, whereas nearly all participants are able to provide urine. The strengths of this meta-analysis are its large size, the carefully harmonised denominator, and the use of Bayesian random-effects and mixed-effects models to predict yields; however, data were geographically restricted, clinically diagnosed tuberculosis was not considered in the denominator, and little information exists on strategies for obtaining sputum samples.
FUNDING
FIND, the Global Alliance for Diagnostics.
Topics: Humans; Male; Female; Sputum; Bayes Theorem; Cross-Sectional Studies; Tuberculosis; Lipopolysaccharides; HIV Infections; Sensitivity and Specificity; Mycobacterium tuberculosis
PubMed: 37202025
DOI: 10.1016/S2214-109X(23)00135-3 -
Frontiers in Cellular and Infection... 2023The GeneXpert MTB/RIF assay (Xpert) is a diagnostic tool that has been shown to significantly improve the accuracy of tuberculosis (TB) detection in clinical settings,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The GeneXpert MTB/RIF assay (Xpert) is a diagnostic tool that has been shown to significantly improve the accuracy of tuberculosis (TB) detection in clinical settings, with advanced sensitivity and specificity. Early detection of TB can be challenging, but Xpert has improved the efficacy of the diagnostic process. Nevertheless, the accuracy of Xpert varies according to different diagnostic specimens and TB infection sites. Therefore, the selection of adequate specimens is critical when using Xpert to identify suspected TB. As such, we have conducted a meta-analysis to evaluate the effectiveness of Xpert for diagnosis of different TB types using several specimens.
METHODS
We conducted a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the World Health Organization clinical trials registry center, covering studies published from Jan 2008 to July 2022. Data were extracted using an adapted version of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies. Where appropriate, meta-analysis was performed using random-effects models. The risk of bias and level of evidence was assessed using the Quality in Prognosis Studies tool and a modified version of the Grading of Recommendations Assessment, Development, and Evaluation. RStudio was utilized to analyze the results, employing the , , and packages.
RESULTS
After excluding duplicates, a total of 2163 studies were identified, and ultimately, 144 studies from 107 articles were included in the meta-analysis based on predetermined inclusion and exclusion criteria. Sensitivity, specificity and diagnostic accuracy were estimated for various specimens and TB types. In the case of pulmonary TB, Xpert using sputum (0.95 95%CI 0.91-0.98) and gastric juice (0.94 95%CI 0.84-0.99) demonstrated similarly high sensitivity, surpassing other specimen types. Additionally, Xpert exhibited high specificity for detecting TB across all specimen types. For bone and joint TB, Xpert, based on both biopsy and joint fluid specimens, demonstrated high accuracy in TB detection. Furthermore, Xpert effectively detected unclassified extrapulmonary TB and tuberculosis lymphadenitis. However, the Xpert accuracy was not satisfactory to distinguish TB meningitis, tuberculous pleuritis and unclassified TB.
CONCLUSIONS
Xpert has exhibited satisfactory diagnostic accuracy for most TB infections, but the efficacy of detection may vary depending on the specimens analyzed. Therefore, selecting appropriate specimens for Xpert analysis is essential, as using inadequate specimens can reduce the ability to distinguish TB.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=370111, identifier CRD42022370111.
Topics: Humans; Mycobacterium tuberculosis; Rifampin; Antibiotics, Antitubercular; Tuberculosis, Pulmonary; Tuberculosis, Meningeal; Latent Tuberculosis; Sensitivity and Specificity
PubMed: 37201118
DOI: 10.3389/fcimb.2023.1149741 -
Microbial Drug Resistance (Larchmont,... Aug 2023The use of tigecycline (TG) for the treatment of is controversial. In this systematic review and meta-analysis, we aimed to better explore the safety and efficacy of... (Meta-Analysis)
Meta-Analysis
The use of tigecycline (TG) for the treatment of is controversial. In this systematic review and meta-analysis, we aimed to better explore the safety and efficacy of TG for the treatment of multi drug-resistant (MDR) Acinetobacter. We searched PubMed/MEDLINE, Scopus, Cochrane Central, and Web of Science to identify studies reporting the clinical and microbiological efficacy and safety of regimens containing TG in patients with drug susceptibility testing (DST)-confirmed MDR , published until December 30, 2022. Observational studies were included if they reported clinical and microbiological efficacy of TG-based regimens. The Newcastle-Ottawa Scale (NOS) and Joana Briggs Institute (JBI) critical appraisal tool were used to assess the quality of included studies. There were 30 observational studies, of which 19 studies were cohort and 11 studies were single group studies. Pooled clinical response and failure rates in the TG-containing regimens group were 58.1 (95% confidence interval [CI] 49.2-66.6) and 40.2 (95% CI 31.1-50.0), respectively. The pooled microbiological response rate was 32.1 (95% CI 19.8-47.5), and the pooled all-cause mortality rate was 41.1 (95% CI 34.1-48.4). Pooled clinical response and failure rates in the colistin-based regimens group were 52.7 (42.7-62.5) and 43.1 (33.1-53.8), respectively. The pooled microbiological response rate was 42.9 (16.2-74.5), and the pooled all-cause mortality rate was 34.3 (26.1-43.5). According to our results, the efficacy of the TG-based regimen is the same as other antibiotics. However, our study showed a high mortality rate and a lower rate of microbiological eradication for TG compared with colistin-based regimen. Therefore, our study does not recommend it for the treatment of MDR . However, this was a prevalence meta-analysis of observational studies, and for better conclusion experimental studies are required.
Topics: Humans; Tigecycline; Anti-Bacterial Agents; Colistin; Acinetobacter baumannii; Microbial Sensitivity Tests; Acinetobacter Infections; Treatment Outcome; Mycobacterium tuberculosis; Drug Resistance, Multiple, Bacterial
PubMed: 37192494
DOI: 10.1089/mdr.2022.0248 -
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 -
The International Journal of... May 2023We performed an analysis of the cost and relative merits of different strategies for the diagnosis of multidrug-resistant/extensively drug-resistant TB (MDR/XDR-TB) in...
We performed an analysis of the cost and relative merits of different strategies for the diagnosis of multidrug-resistant/extensively drug-resistant TB (MDR/XDR-TB) in different settings. We systematically reviewed the published evidence on cost/cost-effectiveness of rapid MDR/pre-XDR-TB and other methods for XDR-TB testing up to September 2022. PRISMA guidelines were followed. Collected data were analysed using Stata v17 software. Cost data were reported in USD ($) and summarised by mean, standard deviation, and range. Country income level was defined according to the World Bank country classification. Three simplified scenarios were also used to explore testing implications, based on low, intermediate and high TB incidence. Of 157 records, 25 studies were included with 24 reporting the cost of Xpert/RIF and two that evaluated the implementation of the MTBDR test. The total rapid test cost ranged from $12.41-$218, including $1.13-$74.60 for reagents/consumables and $0.40-$14.34 for equipment. The cost of MDR/XDR-TB diagnostics is lower in low resource settings. However, the cost-effective implementation of MDR/XDR-TB diagnostic algorithms requires careful consideration of local resources to avoid missed identification and the use of inappropriate regimen.
Topics: Humans; Antitubercular Agents; Extensively Drug-Resistant Tuberculosis; Tuberculosis, Multidrug-Resistant; Microbial Sensitivity Tests; Software; Mycobacterium tuberculosis
PubMed: 37143228
DOI: 10.5588/ijtld.22.0657 -
BMC Infectious Diseases May 2023Carbapenemase-producing Enterobacteriaceae are by far the most public health and urgent clinical problems with antibiotic resistance. They cause longer hospital stays,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Carbapenemase-producing Enterobacteriaceae are by far the most public health and urgent clinical problems with antibiotic resistance. They cause longer hospital stays, more expensive medical care, and greater mortality rates. This systematic review and meta-analysis aimed to indicate the prevalence of carbapenemase-producing Enterobacteriaceae in Ethiopia.
METHODS
This systematic review and meta-analysis was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Electronic databases like PubMed, Google Scholar, CINAHL, Wiley Online Library, African Journal Online, Science Direct, Embase, ResearchGate, Scopus, and the Web of Sciences were used to find relevant articles. In addition, the Joanna Briggs Institute quality appraisal tool was used to assess the quality of the included studies. Stata 14.0 was used for statistical analysis. Heterogeneity was assessed by using Cochran's Q test and I statistics. In addition, publication bias was assessed using a funnel plot and Egger's test. A random effect model was used to estimate the pooled prevalence. Sub-group and sensitivity analysis were also done.
RESULTS
The overall pooled prevalence of carbapenemase-producing Enterobacteriaceae in Ethiopia was 5.44% (95% CI 3.97, 6.92). The prevalence was highest [6.45% (95% CI 3.88, 9.02)] in Central Ethiopia, and lowest [(1.65% (95% CI 0.66, 2.65)] in the Southern Nations and Nationalities People Region. In terms of publication year, 2017-2018 had the highest pooled prevalence [17.44 (95% CI 8.56, 26.32)] and 2015-2016 had the lowest [2.24% (95% CI 0.87, 3.60)].
CONCLUSION
This systematic review and meta-analysis showed a high prevalence of carbapenemase-producing Enterobacteriaceae. So, to alter the routine use of antibiotics, regular drug susceptibility testing, strengthening the infection prevention approach, and additional national surveillance on the profile of carbapenem resistance and their determining genes among Enterobacteriaceae clinical isolates are required.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (2022: CRD42022340181).
Topics: Humans; Ethiopia; Carbapenem-Resistant Enterobacteriaceae; Prevalence; Microbial Sensitivity Tests; Mycobacterium tuberculosis
PubMed: 37138285
DOI: 10.1186/s12879-023-08237-5