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The Indian Journal of Tuberculosis Jan 2024Multi and extensively drug-resistant tuberculosis is a grave cause of global public health concern due to its high mortality and limited treatment options. We conducted... (Meta-Analysis)
Meta-Analysis Review
Multi and extensively drug-resistant tuberculosis is a grave cause of global public health concern due to its high mortality and limited treatment options. We conducted this systemic review and meta-analysis to evaluate the efficacy and safety of bedaquiline and delamanid, which have been added to the WHO-recommended regimen for treating drug-resistant tuberculosis. Electronic databases were searched from their inception until December 1st 2021, for eligible studies assessing the efficacy and safety of bedaquiline and delamanid for treating drug-resistant tuberculosis. Binary outcomes were pooled using a DerSimonian-Laird random-effects model and arcsine transformation and reported on a log scale with a 95% confidence interval (CIs). Twenty-one studies were shortlisted in which bedaquiline, delamanid, and a combination of both were administered in 2477, 937, and 169 patients. Pooled culture conversion at 6 months was 0.801 (p < 0.001), 0.849 (p = 0.059) for bedaquiline and delamanid, respectively, and 0.823 (p = 0.017), concomitantly. In the bedaquiline cohort, the pooled proportion of all-cause mortality at 6 months was reported as 0.074 (p < 0.001), 0.031 (p = 0.372) in the delamanid cohort, and 0.172 in the combined cohort. The incidence of adverse events in the bedaquiline cohort ranged from 11.1% to 95.2%, from 13.2% to 86.2% in the delamanid cohort, and 92.5% in a study in the combined cohort. The incidence of QTC prolongation reported in each cohort is as follows: bedaquiline 0.163 (p < 0.001), delamanid 0.344 (p = 0.272) and combined 0.340 (p < 0.001). Our review establishes the efficacy of delamanid, bedaquiline, and their combined use in treating drug-resistant tuberculosis with reasonable rates of culture conversion, low mortality rates, and safety of co-administration, as seen with their effect on the QTc interval.
Topics: Adult; Humans; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Diarylquinolines; Treatment Outcome; Nitroimidazoles; Oxazoles
PubMed: 38296395
DOI: 10.1016/j.ijtb.2023.05.005 -
Frontiers in Microbiology 2024infection is one of the most common causes of non-tuberculosis mycobacterial (NTM) disease worldwide. However, accurate information on the global prevalence of this...
BACKGROUND
infection is one of the most common causes of non-tuberculosis mycobacterial (NTM) disease worldwide. However, accurate information on the global prevalence of this bacterium is lacking. Therefore, this study was conducted to investigate the prevalence of in clinical and environmental isolates.
METHODS
Databases, including PubMed, Scopus, and the Web of Science, were utilized to gather articles on the prevalence of in clinical and environmental isolates. The collected data were analyzed using Comprehensive Meta-Analysis software.
RESULTS
A total of 118 and 16 studies met the inclusion criteria and were used to analyze the prevalence of in clinical and environmental isolates, respectively. The prevalence of in NTM and environmental isolates were 9.4 and 5.8%, respectively. Subsequent analysis showed an increasing prevalence of over the years. Additionally, the results indicated a significant difference in the prevalence of this bacteria among different regions.
CONCLUSION
The relatively high prevalence of among NTM isolates suggests the need for further implementation of infection control strategies. It is also important to establish appropriate diagnostic criteria and management guidelines for screening this microorganism in environmental samples in order to prevent its spread, given its high prevalence in environmental isolates.
PubMed: 38440139
DOI: 10.3389/fmicb.2024.1321273 -
The Lancet. Microbe Feb 2024Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clinical bedaquiline resistance predominantly involves mutations in mmpR5 (Rv0678). However, mmpR5 resistance-associated variants (RAVs) have a variable relationship with phenotypic Mycobacterium tuberculosis resistance. We did a systematic review to assess the maximal sensitivity of sequencing bedaquiline resistance-associated genes and evaluate the association between RAVs and phenotypic resistance, using traditional and machine-based learning techniques.
METHODS
We screened public databases for articles published from database inception until Oct 31, 2022. Eligible studies performed sequencing of at least mmpR5 and atpE on clinically sourced M tuberculosis isolates and measured bedaquiline minimum inhibitory concentrations (MICs). A bias risk scoring tool was used to identify bias. Individual genetic mutations and corresponding MICs were aggregated, and odds ratios calculated to determine association of mutations with resistance. Machine-based learning methods were used to define test characteristics of parsimonious sets of diagnostic RAVs, and mmpR5 mutations were mapped to the protein structure to highlight mechanisms of resistance. This study was registered in the PROSPERO database (CRD42022346547).
FINDINGS
18 eligible studies were identified, comprising 975 M tuberculosis isolates containing at least one potential RAV (mutation in mmpR5, atpE, atpB, or pepQ), with 201 (20·6%) showing phenotypic bedaquiline resistance. 84 (29·5%) of 285 resistant isolates had no candidate gene mutation. Sensitivity and positive predictive value of taking an any mutation approach was 69% and 14%, respectively. 13 mutations, all in mmpR5, had a significant association with a resistant MIC (adjusted p<0·05). Gradient-boosted machine classifier models for predicting intermediate or resistant and resistant phenotypes both had receiver operator characteristic c statistic of 0·73 (95% CI 0·70-0·76). Frameshift mutations clustered in the α1 helix DNA-binding domain, and substitutions in the α2 and α3 helix hinge region and in the α4 helix-binding domain.
INTERPRETATION
Sequencing candidate genes is insufficiently sensitive to diagnose clinical bedaquiline resistance, but where identified, some mutations should be assumed to be associated with resistance. Genomic tools are most likely to be effective in combination with rapid phenotypic diagnostics. This study was limited by selective sampling in contributing studies and only considering single genetic loci as causative of resistance.
FUNDING
Francis Crick Institute and National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
Topics: United States; Humans; Antitubercular Agents; Diarylquinolines; Tuberculosis; Mycobacterium tuberculosis; Genomics
PubMed: 38215766
DOI: 10.1016/S2666-5247(23)00317-8 -
Lupus May 2024Tuberculosis (TB) is one of the most common infections among systemic lupus erythematosus (SLE) patients. We aimed to evaluate the global prevalence of TB infection and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis (TB) is one of the most common infections among systemic lupus erythematosus (SLE) patients. We aimed to evaluate the global prevalence of TB infection and disease, its type, and medication risk factors in SLE patients.
METHODS
We searched PubMed, Science Direct, EBSCO, and Web of Science databases from inception to April 30, 2023, and included studies assessing TB among SLE patients. We estimated the prevalence of TB disease (including type of TB disease), TB infection, and SLE medication as TB risk factors. Meta-analysis was performed using Stata 14.2 and Review Manager 5.3.
RESULTS
Twenty-seven studies met the eligibility criteria. The global prevalence of TB disease was 4% (95% confidence interval (CI): 3-4%, = 25) and TB infection was 18% (95% CI: 10-26%, = 3). The pooled prevalence of pulmonary TB, extrapulmonary TB, and disseminated TB were 2% (95% CI: 2-3%, = 20), 1% (95% CI: 1-2%, = 17), and 1% (95% CI: 0-1%, = 6), respectively. The 1-year cumulative glucocorticoid (GC) dose in SLE patients contracting TB was higher than in those without TB, having a mean difference of 2.56 (95% CI: 0.22-4.91, < .00001, = 3). The odd ratio of TB was 2.11 (95% CI: 1.01-4.41, = .05, = 3) in SLE patients receiving methylprednisolone (MP) pulse therapy as compared to those without MP pulse therapy. Other immunosuppressive agents were not significantly associated with TB.
CONCLUSION
TB prevalence in SLE was relatively high and associated with GC. Awareness of TB and lowering GC dose are warranted to alleviate the TB burden in SLE.
Topics: Humans; Lupus Erythematosus, Systemic; Tuberculosis; Risk Factors; Glucocorticoids; Immunosuppressive Agents
PubMed: 38490946
DOI: 10.1177/09612033241239504 -
AIDS (London, England) Jul 2024Children and adolescents with HIV infection are well known to face a heightened risk of tuberculosis. However, the exact mortality rates and temporal trends of those... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Children and adolescents with HIV infection are well known to face a heightened risk of tuberculosis. However, the exact mortality rates and temporal trends of those with HIV-tuberculosis (TB) co-infection remain unclear. We aimed to identify the overall mortality and temporal trends within this population.
METHODS
PubMed, Web of Science, and Embase were employed to search for publications reporting on the mortality rates of children and adolescents with HIV-TB co-infection from inception to March 2, 2024. The outcome is the mortality rate for children and adolescents with HIV-TB co-infection during the follow-up period. In addition, we evaluate the temporal trends of mortality.
RESULTS
During the follow-up period, the pooled mortality was 16% [95% confidence interval (CI) 13-20]. Single infection of either HIV or TB exhibit lower mortality rates (6% and 4%, respectively). We observed elevated mortality risks among individuals aged less than 12 months, those with extrapulmonary TB, poor adherence to ART, and severe immunosuppression. In addition, we observed a decreasing trend in mortality before 2008 and an increasing trend after 2008, although the trends were not statistically significant ( P = 0.08 and 0.2 respectively).
CONCLUSIONS
Children and adolescents with HIV-TB co-infection bear a significant burden of mortality. Timely screening, effective treatment, and a comprehensive follow-up system contribute to reducing the mortality burden in this population.
Topics: Humans; HIV Infections; Coinfection; Adolescent; Tuberculosis; Child; Child, Preschool; Infant; Male; Female; Survival Analysis
PubMed: 38499478
DOI: 10.1097/QAD.0000000000003886 -
Clinical Microbiology and Infection :... Nov 2023Limited data exist on assessing the risk of active tuberculosis (TB) in immunocompromised individuals during screening for latent tuberculosis infection (LTBI). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Limited data exist on assessing the risk of active tuberculosis (TB) in immunocompromised individuals during screening for latent tuberculosis infection (LTBI).
OBJECTIVES
To assess the risk of progression to active TB for indeterminate interferon-γ release assays (IGRA) results in immunocompromised individuals during screening for LTBI.
DATA SOURCES
PubMed, Embase, Web of Science, and the Cochrane Library were searched without start date or language restrictions on 18 April 2023.
STUDY ELIGIBILITY CRITERIA
Cohort study or randomized controlled trials that investigated the risk of progression to active TB for indeterminate IGRA during LTBI screening.
PARTICIPANTS
Immunocompromised individuals. TEST: IGRA (T-SPOT.TB and QuantiFERON).
REFERENCE STANDARD
None.
ASSESSMENT OF RISK OF BIAS
A modified version of the Newcastle-Ottawa Scale.
METHODS OF DATA SYNTHESIS
Fixed effects meta-analysis was used to obtain two pooled risk ratios (RRs). RR-ip represented disease progression rate in untreated individuals with indeterminate IGRA versus positive IGRA. RR-in represented disease progression rate in untreated individuals with indeterminate IGRA versus negative IGRA.
RESULTS
Among the 5102 identified studies, 28 (14 792 immunocompromised individuals) were included. The pooled RR-ip and RR-in for cumulative incidence were 0.51 (95% CI, 0.32-0.82; I = 0%) and 2.94 (95% CI, 1.78-4.85; I = 0%), respectively. In addition, 11 studies reporting person-year data were included to verify the reliability of cumulative incidence results. The pooled RR-ip and RR-in for person-year incidence were 0.40 (95% CI, 0.19-0.82; I = 13%) and 2.67 (95% CI, 1.24-5.79; I = 23%), respectively.
DISCUSSION
Indeterminate IGRA results in immunocompromised individuals may represent an intermediate risk of progression to active TB, with half the risk for positive results and three times for negative results. Proper follow-up and management of patients with indeterminate results are crucial for mitigating progression risk and improving patient outcomes.
Topics: Humans; Immunocompromised Host; Interferon-gamma Release Tests; Disease Progression; Latent Tuberculosis; Tuberculosis; Mass Screening
PubMed: 37422080
DOI: 10.1016/j.cmi.2023.07.003 -
PloS One 2023To date, isoniazid mono-resistant tuberculosis (TB) is becoming an emerging global public health problem. It is associated with poor treatment outcome. Different studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To date, isoniazid mono-resistant tuberculosis (TB) is becoming an emerging global public health problem. It is associated with poor treatment outcome. Different studies have assessed the treatment outcome of isoniazid mono-resistant TB cases, however, the findings are inconsistent and there is limited global comprehensive report. Thus, this study aimed to assess the poor treatment outcome and its associated risk factors among patients with isoniazid mono-resistant TB.
METHODS
Studies that reported the treatment outcomes and associated factors among isoniazid mono-resistant TB were searched from electronic databases and other sources. We used Joana Briggs Institute critical appraisal tool to assess the study's quality. We assessed publication bias through visual inspection of the funnel plot and confirmed by Egger's regression test. We used STATA version 17 for statistical analysis.
RESULTS
Among 347 studies identified from the whole search, data were extracted from 25 studies reported from 47 countries. The pooled successful and poor treatment outcomes were 78% (95%CI; 74%-83%) and 22% (95%CI; 17%-26%), respectively. Specifically, complete, cure, treatment failure, mortality, loss to follow-up and relapse rates were 34%(95%CI; 17%-52%), 62% (95%CI; 50%-73%), 5% (95%CI; 3%-7%), 6% (95%CI; 4%-8%), 12% (95%CI; 8%-17%), and 1.7% (95%CI; 0.4%-3.1%), respectively. Higher prevalence of pooled poor treatment outcome was found in the South East Asian Region (estimate; 40%, 95%C; 34%-45%), and African Region (estimate; 33%, 95%CI; 24%-42%). Previous TB treatment (OR; 1.74, 95%CI; 1.15-2.33), having cancer (OR; 3.53, 95%CI; 1.43-5.62), and being initially smear positive (OR; 1.26, 95%CI; 1.08-1.43) were associated with poor treatment outcome. While those patients who took rifampicin in the continuation phase (OR; 0.22, 95%CI; 0.04-0.41), had extrapulmonary TB (OR; 0.70, 95%CI; 0.55-0.85), and took second-line injectable drugs (OR; 0.54, 95%CI; 0.33-0.75) had reduced risk of poor treatment outcome.
CONCLUSION
Isoniazid mono-resistant TB patients had high poor treatment outcome. Thus, determination of isoniazid resistance pattern for all bacteriologically confirmed TB cases is critical for successful treatment outcome. PROSPERO registration number: CRD42022372367.
Topics: Humans; Isoniazid; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Risk Factors; Treatment Outcome
PubMed: 37467275
DOI: 10.1371/journal.pone.0286194 -
Clinical Microbiology and Infection :... Feb 2024Contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are at risk of developing TB disease. Tuberculosis preventive treatment (TPT) is an intervention that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are at risk of developing TB disease. Tuberculosis preventive treatment (TPT) is an intervention that can potentially reduce this risk.
OBJECTIVES
To evaluate the effectiveness and safety of TPT for contacts of patients with MDR-TB.
DATA SOURCES
EMBASE, PubMed, Web of Science, and the Cochrane Library were searched for eligible studies on 24 July 2023, without start date restrictions.
STUDY ELIGIBILITY CRITERIA
We included studies that compared TPT with no treatment in contacts of patients with MDR-TB and reported outcomes of progression to TB disease.
PARTICIPANTS
Contacts of patients with MDR-TB.
INTERVENTIONS
TPT.
ASSESSMENT OF RISK OF BIAS
A modified version of the Newcastle-Ottawa Scale was used.
METHODS OF DATA SYNTHESIS
Random-effects meta-analysis was utilized to calculate the relative risk for disease progression to TB in contacts of patients with MDR-TB who received TPT compared to those who did not. Additionally, completion, adverse effect, and discontinued rates were assessed.
RESULTS
Involving 1105 individuals from 11 studies, the pooled relative risk for disease progression in contacts receiving TPT versus those without treatment was 0.34 (95% CI: 0.16-0.72). Subgroup analysis indicated a lower pooled relative risk for regimens based on the drug-resistance profile of the index patients with TB compared to uniform treatment regimens (0.22 [95% CI: 0.06-0.84] vs. 0.49 [95% CI: 0.17-1.35]), although not statistically significant. The pooled completed rate was 83.8%, adverse effect rate was 22.9%, and discontinued rate was 6.5%. After excluding the levofloxacin and pyrazinamide regimen study, the completed rate increased to 88.0%, and adverse effects and discontinued rates decreased to 8.0% and 4.0%, respectively.
DISCUSSION
TPT reduces TB disease progression risk in contacts of patients with MDR-TB. Tailored TPT regimens based on drug-resistance profiles may offer additional benefits. Furthermore, efforts to improve completed rates and manage adverse effects are essential for optimizing effectiveness and safety.
Topics: Humans; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Pyrazinamide; Levofloxacin; Drug-Related Side Effects and Adverse Reactions; Disease Progression
PubMed: 37741621
DOI: 10.1016/j.cmi.2023.09.015 -
Cureus Mar 2024Bacillus Calmette-Guérin (BCG) vaccination remains a cornerstone in global efforts to combat tuberculosis (TB), a persistent public health threat worldwide. The purpose... (Review)
Review
Bacillus Calmette-Guérin (BCG) vaccination remains a cornerstone in global efforts to combat tuberculosis (TB), a persistent public health threat worldwide. The purpose of this systematic review is to find out how well BCG revaccination protects against TB. This systematic review synthesized recent studies investigating the efficacy of BCG vaccination in preventing TB infection and disease. A total of 15 relevant publications were identified through a comprehensive search across multiple databases, including Cochrane Library, PubMed, Medline, and Scopus. The inclusion criteria encompassed studies involving humans, written in English, and categorized as case-control, cohort, meta-analysis, or full-text. Studies were selected based on their relevance to BCG revaccination and protection against TB, and a standardized data extraction form was used to gather pertinent information from each study. Quality assessment was conducted using established tools to evaluate the rigor, study design, and risk of bias in each included study. The findings revealed significant insights into BCG's effectiveness across different populations and age groups. Several studies demonstrated a substantial reduction in latent TB infection (LTBI) and incidence rates of TB following BCG vaccination. However, the protective efficacy of BCG revaccination varied across studies and populations, with some indicating modest protection against TB disease development, particularly in high-risk populations like healthcare workers. Furthermore, investigations into the immunological mechanisms underlying BCG's protective efficacy provided valuable insights into cytokine/chemokine profiles and immunomodulatory properties.
PubMed: 38646352
DOI: 10.7759/cureus.56643 -
BMC Infectious Diseases Apr 2024Tuberculosis (TB) ranks as the second leading cause of death globally among all infectious diseases. This problem is likely due to the lack of biomarkers to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis (TB) ranks as the second leading cause of death globally among all infectious diseases. This problem is likely due to the lack of biomarkers to differentiate the heterogeneous spectrum of infection. Therefore, the first step in solving this problem is to identify biomarkers to distinguish the different disease states of an individual and treat them accordingly. Circulating microRNA (miRNA) biomarkers are promising candidates for various diseases. In fact, we are yet to conceptualize how miRNA expression influences and predicts TB disease outcomes. Thus, this systematic review and meta-analysis aimed to assess the diagnostic efficacy of circulating miRNAs in Latent TB (LTB) and Active Pulmonary TB (PTB).
METHODS
Literature published between 2012 and 2021 was retrieved from PubMed, Web of Science, Cochrane, Scopus, Embase, and Google Scholar. Articles were screened based on inclusion and exclusion criteria, and their quality was assessed using the QUADAS-2 tool. Funnel plots and forest plots were generated to assess the likelihood of study bias and heterogeneity, respectively.
RESULTS
After the screening process, seven articles were selected for qualitative analysis. The study groups, which consisted of Healthy Control (HC) vs. TB and LTB vs. TB, exhibited an overall sensitivity of 81.9% (95% CI: 74.2, 87.7) and specificity of 68.3% (95% CI: 57.8, 77.2), respectively. However, our meta-analysis results highlighted two potentially valuable miRNA candidates, miR-197 and miR-144, for discriminating TB from HC. The miRNA signature model (miR197-3p, miR-let-7e-5p, and miR-223-3p) has also been shown to diagnose DR-TB with a sensitivity of 100%, but with a compromised specificity of only 75%.
CONCLUSION
miRNA biomarkers show a promising future for TB diagnostics. Further multicentre studies without biases are required to identify clinically valid biomarkers for different states of the TB disease spectrum.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42022302729).
Topics: Humans; MicroRNAs; Tuberculosis; Tuberculosis, Pulmonary; Biomarkers; Latent Tuberculosis
PubMed: 38622570
DOI: 10.1186/s12879-024-09232-0