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Medicine Jun 2023Interleukin-4 (IL-4) is an important cytokine in the Th2 differentiation of CD4+ T cells, which modulates immune responses and participates in host defense against... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Interleukin-4 (IL-4) is an important cytokine in the Th2 differentiation of CD4+ T cells, which modulates immune responses and participates in host defense against Mycobacterium tuberculosis. The present study aimed to evaluate the significance of IL-4 concentration in patients with tuberculosis. Data from this study will be helpful in understanding the immunological mechanisms of tuberculosis and in clinical practice.
METHOD
A data search was conducted from January 1995 to October 2022 in electronic bibliographic databases such as China National Knowledge Infrastructure, Wan Fang, Embase, Web of Science, and PubMed. The Newcastle-Ottawa Scale was used to assess the quality of the included studies. Heterogeneity between the studies was assessed using I2 statistics. Publication bias was determined by funnel plot, and Egger's test was used to confirm the presence of publication bias. All qualified studies and statistical analyses were performed using Stata 11.0.
RESULTS
Fifty-one eligible studies comprising 4317 subjects were included in the meta-analysis. The results depicted a considerably increased level of serum IL-4 in patients with tuberculosis than in the controls (standard mean difference [SMD] = 0.630, [95% confidence interval (CI), 0.162-1.092]). However, there was no significant difference in plasma IL-4 levels between patients with TB and controls (SMD = 0.290, [95% CI, -0.430 to 1.010]). In addition, the infection status, TB focus location, drug resistance, race, research design type, and detection method divided the subjects into different subgroups for the meta-analysis. The results of the comparison of healthy controls and TB subjects showed that in the Asian population, the serum IL-4 level in patients with TB was higher than that in controls (SMD = 0.887, [95% CI, 0.202 to -1.573]) and patients with active TB as well as people with pulmonary TB showed increased serum IL-4 levels compared to controls (SMD = 0.689, [95% CI, 0.152-1.226]). In the case of the control group with latent TB, the active TB group had higher serum IL-4 levels than the control group (SMD = 0.920, [95% CI, 0.387-1.452]).
CONCLUSION
The present meta-analysis showed that serum IL-4 varied in healthy individuals and patients with TB. Patients with active TB may also exhibit higher IL-4 concentrations.
Topics: Humans; Interleukin-4; Tuberculosis; Mycobacterium tuberculosis; Cytokines; China
PubMed: 37327256
DOI: 10.1097/MD.0000000000034041 -
Drug Target Insights 2023Tuberculosis (TB) mains a deadly disease affecting one-third population globally. Long turnaround time and poor sensitivity of the conventional diagnostics are the major... (Review)
Review
BACKGROUND
Tuberculosis (TB) mains a deadly disease affecting one-third population globally. Long turnaround time and poor sensitivity of the conventional diagnostics are the major impediments for faster diagnosis of to prevent drug resistance. To overcome these issues, molecular diagnostics have been developed. They offer enhanced sensitivity but require sophisticated infrastructure, skilled manpower and remain expensive.
METHODS
In that context, loop-mediated isothermal amplification (LAMP) assay, recommended by the WHO in 2016 for TB diagnosis, sounds as a promising alternative that facilitates visual read outs. Therefore, the aim of the present study is to conduct a meta-analysis to assess the diagnostic efficiency of LAMP for the detection of a panel of . following PRISMA guidelines using scientific databases. From 1600 studies reported on the diagnosis of ., a selection of 30 articles were identified as eligible to meet the criteria of LAMP based diagnosis.
RESULTS
It was found that most of the studies were conducted in high disease burden nations such as India, Thailand, and Japan with sputum as the most common specimen to be used for LAMP assay. Furthermore, gene and fluorescence-based detections ranked as the most used target and method respectively. The accuracy and precision rates mostly varied between 79.2% to 99.3% and 73.9% to 100%, respectively. Lastly, a quality assessment based on QUADAS-2 of bias and applicability was conducted.
CONCLUSION
LAMP technology could be considered as a feasible alternative to current diagnostics considering high burden for rapid testing in low resource regions.
PubMed: 37304408
DOI: 10.33393/dti.2023.2596 -
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 -
Open Forum Infectious Diseases May 2023A systematic review showed that the accuracy of antigen-based skin tests (TBSTs) for tuberculosis is similar to that of interferon γ release assay, but the safety of...
BACKGROUND
A systematic review showed that the accuracy of antigen-based skin tests (TBSTs) for tuberculosis is similar to that of interferon γ release assay, but the safety of TBSTs has not been systematically reviewed.
METHODS
We searched for studies reporting injection site reactions (ISRs) and systemic adverse events associated with TBSTs. We searched Medline, Embase, e-library, the Chinese Biomedical Literature Database, and the China National Knowledge Infrastructure database for studies through 30 July 2021, and the database search was updated until 22 November 2022.
RESULTS
We identified 7 studies for Cy-Tb (Serum Institute of India), 7 (including 2 found through the updated search) for C-TST (Anhui Zhifei Longcom), and 11 for Diaskintest (Generium). The pooled risk of any injection site reactions (ISRs) due to Cy-Tb (n = 2931; 5 studies) did not differ significantly from that for tuberculin skin tests (TSTs; risk ratio, 1.05 [95% confidence interval, .70-1.58]). More than 95% of ISRs were reported as mild or moderate; common ISRs included pain, itching, and rash. In 1 randomized controlled study, 49 of 153 participants (37.6%) given Cy-Tb experience any systemic adverse event (eg, fever and headache), compared with 56 of 149 participants (37.6%) given TST (risk ratio, 0.85 [95% confidence interval, .6-1.2]). In a randomized controlled study in China (n = 14 579), the frequency of systemic adverse events in participants given C-TST was similar to that for TST, and the frequency of ISRs was similar to or lower than that for TST. Reporting of the safety data on Diaskintest was not standardized, precluding meta-analysis.
CONCLUSION
The safety profile of TBSTs appears similar to that of TSTs and is associated with mostly mild ISRs.
PubMed: 37234516
DOI: 10.1093/ofid/ofad228 -
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 -
Diagnostics (Basel, Switzerland) May 2023Lung ultrasound (LUS) is a widely available technique allowing rapid bedside detection of different respiratory disorders. Its reliability in the diagnosis of... (Review)
Review
BACKGROUND
Lung ultrasound (LUS) is a widely available technique allowing rapid bedside detection of different respiratory disorders. Its reliability in the diagnosis of community-acquired lung infection has been confirmed. However, its usefulness in identifying infections caused by specific and less common pathogens (e.g., in immunocompromised patients) is still uncertain.
METHODS
This systematic review aimed to explore the most common LUS patterns in infections caused by intracellular, fungal pathogens or mycobacteria.
RESULTS
We included 17 studies, reporting a total of 274 patients with , 30 with fungal infection and 213 with pulmonary tuberculosis (TB). Most of the studies on in children found a specific LUS pattern, mainly consolidated areas associated with diffuse B lines. The typical LUS pattern in TB consisted of consolidation and small subpleural nodes. Only one study on fungal disease reported LUS specific patterns (e.g., indicating "halo sign" or "reverse halo sign").
CONCLUSIONS
Considering the preliminary data, LUS appears to be a promising point-of-care tool, showing patterns of atypical pneumonia and TB which seem different from patterns characterizing common bacterial infection. The role of LUS in the diagnosis of fungal disease is still at an early stage of exploration. Large trials to investigate sonography in these lung infections are granted.
PubMed: 37175003
DOI: 10.3390/diagnostics13091612 -
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