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Scientific Reports Jun 2024Accurate tuberculosis (TB) diagnosis remains challenging, especially in resource-limited settings. This study aims to assess the diagnostic performance of the QIAreach... (Meta-Analysis)
Meta-Analysis Comparative Study
Accurate tuberculosis (TB) diagnosis remains challenging, especially in resource-limited settings. This study aims to assess the diagnostic performance of the QIAreach QuantiFERON-TB (QFT) assay, with a specific focus on comparing its diagnostic performance with the QuantiFERON-TB Gold Plus (QFT-Plus). We systematically reviewed relevant individual studies on PubMed, Scopus, and Web of Science up to January 20, 2024. The focus was on evaluating the diagnostic parameters of the QIAreach QFT assay for TB infection, which included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and concordance with the QFT-Plus assay. QIAreach QFT demonstrated strong diagnostic performance with a pooled sensitivity of 99% (95% CI 95-100%) and specificity of 94% (95% CI 85-97%). Additionally, it showed a PLR of 15.6 (95% CI 6.5-37.5) and NLR of 0.01 (95% CI 0-0.03). The pooled PPV and NPV were 88% (95% CI 70-98%) and 100% (95% CI 99-100%), respectively. Concordance analysis with QFT-Plus revealed a pooled positive percent agreement of 98% (95% CI 88-100%) and pooled negative percent agreement of 91% (95% CI 81-97%), with a pooled overall percent agreement of 92% (95% CI 83-98). In conclusion, QIAreach QFT has shown promising diagnostic performance, with a strong concordance with QFT-Plus. However, further studies are needed to comprehensively evaluate its diagnostic performance in the context of TB infection.
Topics: Humans; Tuberculosis; Sensitivity and Specificity; Interferon-gamma Release Tests; Mycobacterium tuberculosis
PubMed: 38914731
DOI: 10.1038/s41598-024-65663-4 -
Ethiopian Journal of Health Sciences Sep 2023Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar... (Review)
Review
BACKGROUND
Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar clinical presentations to tuberculosis, leading to inappropriate treatment and increased morbidity and mortality rates. This literature review aims to provide an overview of the prevalence, clinical manifestations, diagnosis, and management of NTM infections in Africa.
METHODS
A systematic search was performed using various electronic databases including PubMed, Scopus, and Web of Science. The search was limited to studies published in the English language from 2000 to 2021. The following keywords were used: "non-tuberculous mycobacteria", "NTM", "Africa", and "prevalence". Studies that focused solely on the Mycobacterium tuberculosis complex or those that did not report prevalence rates were excluded. Data extraction was performed on eligible studies. Overall, a total of 32 studies met the inclusion criteria and were included in this review.
RESULTS
In our literature review, we identified a total of 32 studies that reported non-tuberculosis mycobacteria (NTM) in Africa. The majority of these studies were conducted in South Africa, followed by Ethiopia and Nigeria. The most commonly isolated NTM species were Mycobacterium avium complex (MAC), Mycobacterium fortuitum, and Mycobacterium abscessus. Many of the studies reported a high prevalence of NTM infections among HIV-positive individuals. Other risk factors for NTM infection included advanced age, chronic lung disease, and previous tuberculosis infection.
CONCLUSION
In conclusion, this literature review highlights the significant burden of non-tuberculosis mycobacteria infections in Africa. The prevalence of these infections is high, and they are often misdiagnosed due to their similarity to tuberculosis. The lack of awareness and diagnostic tools for non-tuberculosis mycobacteria infections in Africa is a major concern that needs to be addressed urgently. It is crucial to improve laboratory capacity and develop appropriate diagnostic algorithms for these infections.
Topics: Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Africa; Prevalence
PubMed: 38784502
DOI: 10.4314/ejhs.v33i5.21 -
The American Journal of Tropical... Jun 2024Substantial tuberculosis transmission occurs outside of households, and tuberculosis surveillance in schools has recently been proposed. However, the yield of... (Meta-Analysis)
Meta-Analysis
Substantial tuberculosis transmission occurs outside of households, and tuberculosis surveillance in schools has recently been proposed. However, the yield of tuberculosis outcomes from school contacts is not well characterized. We assessed the prevalence of Mycobacterium tuberculosis infection among close school contacts by performing a systematic review. We searched PubMed, Elsevier, China National Knowledge Infrastructure, and Wanfang databases. Studies reporting the number of children who were tested overall and who tested positive were included. Subgroup analyses were performed by study location, index case bacteriological status, type of school, and other relevant factors. In total, 28 studies including 54,707 school contacts screened for M. tuberculosis infection were eligible and included in the analysis. Overall, the prevalence of M. tuberculosis infection determined by the QuantiFERON Gold in-tube test was 33.2% (95% CI, 0.0-73.0%). The prevalences of M. tuberculosis infection based on the tuberculin skin test (TST) using 5 mm, 10 mm, and 15 mm as cutoffs were 27.2% (95% CI, 15.1-39.3%), 24.3% (95% CI, 15.3-33.4%), and 12.7% (95% CI, 6.3-19.0%), respectively. The pooled prevalence of M. tuberculosis infection (using a TST ≥5-mm cutoff) was lower in studies from China (22.8%; 95% CI, 16.8-28.8%) than other regions (36.7%; 95% CI, 18.1-55.2%). The pooled prevalence of M. tuberculosis infection was higher when the index was bacteriologically positive (43.6% [95% CI, 16.5-70.8%] versus 23.8% [95% CI, 16.2-31.4%]). These results suggest that contact investigation and general surveillance in schools from high-burden settings merit consideration as means to improve early case detection in children.
Topics: Humans; Schools; Mycobacterium tuberculosis; Tuberculosis; Prevalence; Tuberculin Test; Contact Tracing; Child; China
PubMed: 38653232
DOI: 10.4269/ajtmh.23-0038 -
PLoS Pathogens Apr 2024Drug-resistant tuberculosis (DR-TB) threatens progress in the control of TB. Mathematical models are increasingly being used to guide public health decisions on managing...
Drug-resistant tuberculosis (DR-TB) threatens progress in the control of TB. Mathematical models are increasingly being used to guide public health decisions on managing both antimicrobial resistance (AMR) and TB. It is important to consider bacterial heterogeneity in models as it can have consequences for predictions of resistance prevalence, which may affect decision-making. We conducted a systematic review of published mathematical models to determine the modelling landscape and to explore methods for including bacterial heterogeneity. Our first objective was to identify and analyse the general characteristics of mathematical models of DR-mycobacteria, including M. tuberculosis. The second objective was to analyse methods of including bacterial heterogeneity in these models. We had different definitions of heterogeneity depending on the model level. For between-host models of mycobacterium, heterogeneity was defined as any model where bacteria of the same resistance level were further differentiated. For bacterial population models, heterogeneity was defined as having multiple distinct resistant populations. The search was conducted following PRISMA guidelines in five databases, with studies included if they were mechanistic or simulation models of DR-mycobacteria. We identified 195 studies modelling DR-mycobacteria, with most being dynamic transmission models of non-treatment intervention impact in M. tuberculosis (n = 58). Studies were set in a limited number of specific countries, and 44% of models (n = 85) included only a single level of "multidrug-resistance (MDR)". Only 23 models (8 between-host) included any bacterial heterogeneity. Most of these also captured multiple antibiotic-resistant classes (n = 17), but six models included heterogeneity in bacterial populations resistant to a single antibiotic. Heterogeneity was usually represented by different fitness values for bacteria resistant to the same antibiotic (61%, n = 14). A large and growing body of mathematical models of DR-mycobacterium is being used to explore intervention impact to support policy as well as theoretical explorations of resistance dynamics. However, the majority lack bacterial heterogeneity, suggesting that important evolutionary effects may be missed.
Topics: Humans; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant; Models, Theoretical; Antitubercular Agents
PubMed: 38598556
DOI: 10.1371/journal.ppat.1011574 -
Journal of Global Antimicrobial... Jun 2024This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and M. avium complex (MAC), considering BDQ as a repurposed drug for non-tuberculous mycobacteria (NTM) infections.
METHODS
We conducted a systematic review of publications in PubMed/ MEDLINE, Web of Science, and Embase up to 15 April 2023. Studies were included if they followed the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). Using a random effects model, we assessed the overall in vitro BDQ resistance rate in clinical isolates of MABS and MAC. Sources of heterogeneity were analysed using Cochran's Q and the I statistic. All analyses were performed using CMA V3.0.
RESULTS
A total of 24 publications (19 reports for MABS and 11 for MAC) were included. Using 1 µg/mL and 2 µg/mL as the breakpoint for BDQ resistance, the pooled rates of in vitro BDQ resistance in clinical isolates of MABS were found to be 1.8% (95% confidence interval [CI], 0.7-4.6%) and 1.7% (95% CI, 0.6-4.4%), respectively. In the case of MAC, the pooled rates were 1.7% (95% CI, 0.4-6.9%) and 1.6% (95% CI, 0.4-6.8%) for 1 µg/mL and 2 µg/mL, respectively.
CONCLUSION
This study reports the prevalence of BDQ resistance in clinical isolates of MABS and MAC. The findings suggest that BDQ holds potential as a repurposed drug for treating MABS and MAC infections.
Topics: Diarylquinolines; Humans; Microbial Sensitivity Tests; Mycobacterium abscessus; Mycobacterium avium Complex; Mycobacterium Infections, Nontuberculous; Antitubercular Agents; Drug Resistance, Bacterial; Mycobacterium avium-intracellulare Infection
PubMed: 38561143
DOI: 10.1016/j.jgar.2024.03.009 -
Mycobacterium tuberculosis latent infection in healthcare students: systematic review of prevalence.Revista Da Escola de Enfermagem Da U S P 2024The aim of this study was to synthesize the evidence on the prevalence of latent Mycobacterium tuberculosis infection (LTBI) among undergraduate health care students. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study was to synthesize the evidence on the prevalence of latent Mycobacterium tuberculosis infection (LTBI) among undergraduate health care students.
METHODS
A systematic review of prevalence with meta-analysis was conducted. Prospective and retrospective cohorts and cross-sectional studies involving probable exposure to M. tuberculosis during undergraduate education, along with the tuberculin skin test (TST) or interferon-γ release assay (IGRA) for investigation of latent tuberculosis were searched. Searches were conducted in MEDLINE, CINAHL, EMBASE, LILACS, Scopus, and Web of Science databases. Independent reviewers were responsible for the selection and inclusion of studies. Data were extracted, critically appraised, and synthesized using the JBI approach. PRISMA was used to report the study.
RESULTS
Twenty-two studies were analyzed. The overall prevalence in healthcare undergraduate students was 12.53%.
CONCLUSION
The prevalence of LTBI in undergraduate health students was high for such a highly educated population. Screening with TST and/or IGRA and chemoprophylaxis, when necessary, should be provided to undergraduate health students when in contact with respiratory symptomatic patients.
Topics: Humans; Mycobacterium tuberculosis; Prevalence; Cross-Sectional Studies; Retrospective Studies; Prospective Studies; Latent Tuberculosis; Students
PubMed: 38488508
DOI: 10.1590/1980-220X-REEUSP-2023-0238en -
Frontiers in Immunology 2024First described by Wallis et al. in 2001 for the assessment of TB drugs, the direct mycobacterial growth inhibition assay (MGIA) offers a tractable tool measuring the...
INTRODUCTION
First described by Wallis et al. in 2001 for the assessment of TB drugs, the direct mycobacterial growth inhibition assay (MGIA) offers a tractable tool measuring the combined influences of host immunity, strain virulence and intervention effects. Over the past 13 years, we have led efforts to adapt the direct MGIA for the assessment of TB vaccines including optimisation, harmonisation and validation of BCG vaccine-induced responses as a benchmark, as well as assay transfer to institutes worldwide.
METHODS
We have performed a systematic review on the primary published literature describing the development and applications of the direct MGIA from 2001 to June 2023 in accordance with the PRISMA reporting guidelines.
RESULTS
We describe 63 studies in which the direct MGIA has been applied across species for the evaluation of TB drugs and novel TB vaccine candidates, the study of clinical cohorts including those with comorbidities, and to further understanding of potential immune correlates of protection from TB. We provide a comprehensive update on progress of the assay since its conception and critically evaluate current findings and evidence supporting its utility, highlighting priorities for future directions.
DISCUSSION
While further standardisation and validation work is required, significant advancements have been made in the past two decades. The direct MGIA provides a potentially valuable tool for the early evaluation of TB drug and vaccine candidates, clinical cohorts, and immune mechanisms of mycobacterial control.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023423491.
Topics: Humans; BCG Vaccine; Mycobacterium tuberculosis; Tuberculosis; Tuberculosis Vaccines
PubMed: 38380319
DOI: 10.3389/fimmu.2024.1355983 -
BMC Infectious Diseases Feb 2024We aimed to evaluate the sputum culture conversion time of DR-TB patients and its related factors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aimed to evaluate the sputum culture conversion time of DR-TB patients and its related factors.
METHODS
PubMed, The Cochrane Library, Embase, CINAHL, Web of Science, CNKI, Wan Fang, CBM and VIP databases were electronically searched to collect studies on sputum culture conversion time in patients with DR-TB. Meta-analysis was performed by using the R 4.3.0 version and Stata 16 software.
RESULTS
A total of 45 studies involving 17373 patients were included. Meta-analysis results showed that the pooled median time to sputum culture conversion was 68.57 days (IQR 61.01,76.12). The median time of sputum culture conversion in patients with drug-resistant tuberculosis was different in different WHO regions, countries with different levels of development and different treatment schemes. And female (aHR = 0.59,95%CI: s0.46,0.76), alcohol history (aHR = 0.70,95%CI:0.50,0.98), smoking history (aHR = 0.58,95%CI:0.38,0.88), history of SLD use (aHR = 0.64,95%CI:0.47,0.87), BMI < 18.5 kg/m (aHR = 0.69,95%CI:0.60,0.80), lung cavity (aHR = 0.70,95%CI:0.52,0.94), sputum smear grading at baseline (Positive) (aHR = 0.56,95%CI:0.36,0.87), (grade 1) (aHR = 0.87,95%CI:0.77,0.99), (grade 2) (aHR = 0.81,95%CI:0.69,0.95), (grade 3) (aHR = 0.71,95%CI:0.61,0.84) were the related factor of sputum culture conversion time in patients with DR-TB.
CONCLUSION
Patients with DR-TB in Europe or countries with high level of economic development have earlier sputum culture conversion, and the application of bedaquiline can make patients have shorter sputum culture conversion time. Female, alcohol history, smoking history, history of SLD use, BMI < 18.5 kg/m, lung cavity, sputum smear grading at baseline (Positive, grade 1, grade 2, grade 3) may be risk factors for longer sputum culture conversion time. This systematic review has been registered in PROSPERO, the registration number is CRD42023438746.
Topics: Humans; Female; Antitubercular Agents; Sputum; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Risk Factors; Mycobacterium tuberculosis; Treatment Outcome
PubMed: 38326758
DOI: 10.1186/s12879-024-09009-5 -
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 -
Tuberkuloz Ve Toraks Dec 2023Non-tuberculous mycobacteria (NTM) can cause diseases not only in individuals with compromised immune systems but also in those with normal immune function. This study...
Non-tuberculous mycobacteria (NTM) can cause diseases not only in individuals with compromised immune systems but also in those with normal immune function. This study aimed to compare the prevalence of NTM in Türkiye and worldwide between 2012 and 2022. This study was designed following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedure. A systematic search was conducted between January 2012 and September 2022 using different electronic databases, including Pubmed, Medline, Embase, Web of Science, Ebsco, Scopus, Türk Medline, and Google Scholar. During the literature review process, titles and abstracts were examined and the full texts of the studies were accessed. In 13 research articles from Türkiye included in the study, a total of 17.293 samples were studied and a total of 1304 NTM (7.54%) strains were isolated from these samples. Among the 1304 NTM strains reported from Türkiye, the top three most frequently isolated species were M. abscessus (29.83%), M. lentiflavum (14.97%), M. fortuitum (14.38%). In 35 studies included from around the world, a total of 512.626 samples were studied and a total of 12.631 NTM (2.46%) strains were isolated from these samples. Among the 12631 NTM strains isolated, the top three most frequently isolated species were M. intracellulare (28.13%), M. avium (17.70%) and M. abscessus (14.88%). This study unveiled the global prevalence of NTM-infected patients, detailing species distribution and microbiological diagnostic methods. Variations in NTM spread were observed, influenced by diverse factors.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Prevalence; Turkey
PubMed: 38152011
DOI: 10.5578/tt.20239609