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Frontiers in Immunology 2020Tuberculosis (TB) is a severe infectious disease with devastating effects on global public health. No TB vaccine has yet been approved for use on latent TB infections... (Meta-Analysis)
Meta-Analysis
Tuberculosis (TB) is a severe infectious disease with devastating effects on global public health. No TB vaccine has yet been approved for use on latent TB infections and healthy adults. In this study, we performed a systematic review and meta-analysis to evaluate the immunogenicity and safety of the M72/AS01 and MVA85A subunit vaccines. The M72/AS01 is a novel peptide-based vaccine currently in progress, which may increase the protection level against TB infection. The MVA85A was a viral vector-based TB subunit vaccine being used in the clinical trials. The vaccines mentioned above have been studied in various phase I/II clinical trials. Immunogenicity and safety is the first consideration for TB vaccine development. The PubMed, Embase, and Cochrane Library databases were searched for published studies (until October 2019) to find out information on the M72/AS01 and MVA85A candidate vaccines. The meta-analysis was conducted by applying the standard methods and processes established by the Cochrane Collaboration. Five eligible randomized clinical trials (RCTs) were selected for the meta-analysis of M72/AS01E candidate vaccines. The analysis revealed that the M72/AS01E subunit vaccine had an abundance of polyfunctional M72-specific CD4+ T cells [standardized mean difference (SMD) = 2.37] in the vaccine group versus the control group, the highest seropositivity rate [relative risk (RR) = 5.09]. The M72/AS01E vaccinated group were found to be at high risk of local injection site redness (RR = 2.64), headache (RR = 1.59), malaise (RR = 3.55), myalgia (RR = 2.27), fatigue (RR = 2.16), pain (RR = 3.99), swelling (RR = 5.09), and fever (RR = 2.04) compared to the control groups. The incidences of common adverse events of M72/AS01E were local injection site redness, headache, malaise, myalgia, fatigue, pain, swelling, fever, etc. Six eligible RCTs were selected for the meta-analysis on MVA85A candidate vaccines. The analysis revealed that the subunit vaccine MVA85A had a higher abundance of overall pooled proportion polyfunctional MVA85A-specific CD4+ T cells SMD = 2.41 in the vaccine group vs. the control group, with the highest seropositivity rate [estimation rate (ER) = 0.55]. The MVA85A vaccinated group were found to be at high risk of local injection site redness (ER = 0.55), headache (ER = 0.40), malaise (ER = 0.29), pain (ER = 0.54), myalgia (ER = 0.31), and fever (ER = 0.20). The incidences of common adverse events of MVA85A were local injection site redness, headache, malaise, pain, myalgia, fever, etc. The M72/AS01 and MVA85A vaccines against TB are safe and had immunogenicity in diverse clinical trials. The M72/AS01 and MVA85A vaccines are associated with a mild adverse reaction. The meta-analysis on immunogenicity and safety of M72/AS01 and MVA85A vaccines provides useful information for the evaluation of available subunit vaccines in the clinic.
Topics: Adolescent; Adult; Female; Host-Pathogen Interactions; Humans; Immunogenicity, Vaccine; Infant; Male; Middle Aged; Mycobacterium tuberculosis; Patient Safety; Randomized Controlled Trials as Topic; Treatment Outcome; Tuberculosis; Tuberculosis Vaccines; Vaccines, DNA; Vaccines, Subunit; Young Adult
PubMed: 33133057
DOI: 10.3389/fimmu.2020.01806 -
Frontiers in Public Health 2021Timely and accurate diagnosis of tuberculosis (TB) remains a major challenge. Lipoarabinomannan (LAM) is a specific component of the cell envelope of and is also a... (Meta-Analysis)
Meta-Analysis
Timely and accurate diagnosis of tuberculosis (TB) remains a major challenge. Lipoarabinomannan (LAM) is a specific component of the cell envelope of and is also a potential biomarker for the diagnosis of TB. Recently, the Fujifilm SILVAMP TB LAM test (FujiLAM), as a novel urine lateral flow LAM test, was developed for the diagnosis of TB and is convenient and timely. Because of a difference in the diagnostic value of FujiLAM in the original studies, we conducted a meta-analysis to comprehensively assess the diagnostic value of FujiLAM in TB. We performed a literature search using the PubMed and EMBASE databases and commercial Internet search engines to identify studies. Searches of databases using relevant terms ("tuberculosis" or "TB") and ("Fujifilm SILVAMP TB LAM" or "FujiLAM") were performed. Screening, study reviewing, data extracting and assessing data quality was performed independently by two reviewers. We calculated the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. To minimize potential heterogeneity, we performed subgroup analyses. Nine articles were included in the meta-analysis. When using the microbiological reference standard (MRS), the results showed that the sensitivity and specificity of FujiLAM were 0.70 and 0.93, respectively, in adults with TB, while the sensitivity and specificity of FujiLAM in children with TB were 0.51 and 0.87. When using a comprehensive reference standard (CRS), the sensitivity and specificity of FujiLAM in adults with TB were 0.59 and 0.96, respectively, while the results showed that the sensitivity and specificity of FujiLAM in children with TB were 0.27 and 0.86, respectively. Subgroup analysis showed that FujiLAM had higher diagnostic sensitivity in patients with human immunodeficiency virus infection or CD4 cell counts < 200 cells/μL, both in adults and children. This meta-analysis suggests that FujiLAM has a high value in the diagnosis of adults with TB.
Topics: Adult; Biomarkers; Child; HIV Infections; Humans; Mycobacterium tuberculosis; Sensitivity and Specificity; Tuberculosis
PubMed: 34900905
DOI: 10.3389/fpubh.2021.757133 -
Epidemiology and Infection Feb 2018We performed a systematic review and meta-analyses of studies assessing tuberculosis (TB) patient-related risk factors for transmission of Mycobacterium tuberculosis... (Meta-Analysis)
Meta-Analysis Review
We performed a systematic review and meta-analyses of studies assessing tuberculosis (TB) patient-related risk factors for transmission of Mycobacterium tuberculosis infection. Meta-analyses were conducted for sputum smear-positivity, lung cavitation and HIV seropositivity of index patients with both crude and adjusted odds ratios (AORs) pooled using random effect models. Thirty-seven studies were included in the review. We found that demographic characteristics such as age and sex were not significant risk factors, while behaviours such as smoking and alcohol intake were associated with infectiousness although inconsistently. Treatment delay of >28 days was a significant predictor of greater infectiousness. Contacts of sputum smear-positive index patients were found to be more likely to be infected than contacts of sputum smear-negative patients, with a pooled AOR of 2.15 (95% confidence interval (CI) 1.47-3.17, I 2 = 38%). Similarly, contacts of patients with the cavitary disease were around twice as likely to be infected as contacts of patients without cavitation (pooled AOR 1.9, 95% CI 1.26-2.84, I 2 = 63%). In contrast, HIV seropositive patients were associated with few contact infections than HIV seronegative patients (AOR 0.45, 95% CI 0.26-0.80, I 2 = 52%). In conclusion, behavioural and clinical characteristics of TB patients can be used to identify highly infectious patients for targeted interventions.
Topics: Alcoholic Beverages; Humans; Mycobacterium tuberculosis; Risk Factors; Smoking; Tuberculosis
PubMed: 29338805
DOI: 10.1017/S0950268817003041 -
PLoS Neglected Tropical Diseases Apr 2020Buruli ulcer (BU) is a subcutaneous necrotic infection of the skin caused by Mycobacterium ulcerans. It is the third most common human mycobacterial disease after... (Meta-Analysis)
Meta-Analysis
Buruli ulcer (BU) is a subcutaneous necrotic infection of the skin caused by Mycobacterium ulcerans. It is the third most common human mycobacterial disease after tuberculosis (TB) and leprosy. The available methods for detection of the bacilli in lesions are microscopic detection, isolation and cultivation of the bacterium, histopathology, and polymerase chain reaction (PCR). These methods, although approved by the World Health Organization (WHO), have infrastructural and resource challenges in medical centres and cell-mediated immunity (CMI) and/or serology-based tests have been suggested as easier and more appropriate for accurate assessment of the disease, especially in remote or underdeveloped areas. This study systematically reviewed and conducted a meta-analysis for all research aimed at developing cell-mediated immunity (CMI) and/or serology-based tests for M. ulcerans disease. Information for this review was searched through PubMed and Web of Science databases and identified up to June 2019. References from relevant articles and reports from the WHO Annual Meeting of the Global Buruli Ulcer Initiative were also used. Twelve studies beginning in 1952, that attempted to develop CMI and/or serology-based tests for the disease were identified. These studies addressed issues of specificity and sensitivity in context of antigen composition as well as study heterogeneity and bias. The two main types of antigenic preparations considered were pathogen-derived and recombinant protein preparations. There was slight difference in test performance when M. ulcerans recombinant proteins [positivity: 67.5%; 32.5%] or pathogen-derived [positivity: 76.0%; 24.0%] preparations were used as test antigens among BU patients. However, pathogen-derived preparations were better at differentiating between patients and control groups [odds ratio (OR) of 27.92, 95%CI: 5.05-154.28]. This was followed by tests with the recombinant proteins [OR = 1.23, 95%CI: 0.27-5.62]. Overall, study heterogeneity index, I2 was 92.4% (p = 0.000). It is apparent from this review that standardisation is needed in any future CMI and/or serology-based tests used for M. ulcerans disease.
Topics: Buruli Ulcer; Databases, Factual; Humans; Immunity, Cellular; Leprosy; Mycobacterium ulcerans; Polymerase Chain Reaction; Serologic Tests
PubMed: 32251470
DOI: 10.1371/journal.pntd.0008172 -
The Cochrane Database of Systematic... Dec 2016Nontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium tuberculosis complex, and are commonly found in the environment. Nontuberculous... (Review)
Review
BACKGROUND
Nontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium tuberculosis complex, and are commonly found in the environment. Nontuberculous mycobacteria species (most commonly Mycobacterium avium complex and Mycobacterium abscessus) are isolated from the respiratory tract of approximately 5% to 40% of individuals with cystic fibrosis; they can cause lung disease in people with cystic fibrosis leading to more a rapid decline in lung function and even death in certain circumstances. Although there are guidelines for the antimicrobial treatment of nontuberculous mycobacteria lung disease, these recommendations are not specific for people with cystic fibrosis and it is not clear which antibiotic regimen may be the most effective in the treatment of these individuals. This is an update of a previous review.
OBJECTIVES
The objective of our review was to compare antibiotic treatment to no antibiotic treatment, or to compare different combinations of antibiotic treatment, for nontuberculous mycobacteria lung infections in people with cystic fibrosis. The primary objective was to assess the effect of treatment on lung function and pulmonary exacerbations and to quantify adverse events. The secondary objectives were to assess treatment effects on the amount of bacteria in the sputum, quality of life, mortality, nutritional parameters, hospitalizations and use of oral antibiotics.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 02 September 2016.We also searched a register of ongoing trials and the reference lists of relevant articles and reviews. Date of last search: 03 November 2016.
SELECTION CRITERIA
Any randomized controlled trials comparing nontuberculous mycobacteria antibiotics to no antibiotic treatment, as well as one nontuberculous mycobacteria antibiotic regimen compared to another nontuberculous mycobacteria antibiotic regimen, in individuals with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Data were not collected because in the one trial identified by the search, data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.
MAIN RESULTS
One completed trial was identified by the searches, but data specific to individuals with cystic fibrosis could not be obtained from the pharmaceutical company.
AUTHORS' CONCLUSIONS
This review did not find any evidence for the effectiveness of different antimicrobial treatment for nontuberculous mycobacteria lung disease in people with cystic fibrosis. Until such evidence becomes available, it is reasonable for clinicians to follow published clinical practice guidelines for the diagnosis and treatment of nodular or bronchiectatic pulmonary disease due to Mycobacterium avium complex or Mycobacterium abscessus in patients with cystic fibrosis.
Topics: Anti-Bacterial Agents; Cystic Fibrosis; Drug Therapy, Combination; Humans; Lung Diseases; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria
PubMed: 28000919
DOI: 10.1002/14651858.CD010004.pub4 -
Frontiers in Public Health 2021Drug-resistant tuberculosis (DR-TB), especially multidrug-resistant tuberculosis (MDR-TB) is a public health threat. Little is known about estimates of different... (Meta-Analysis)
Meta-Analysis
Drug-resistant tuberculosis (DR-TB), especially multidrug-resistant tuberculosis (MDR-TB) is a public health threat. Little is known about estimates of different profiles and rates of DR-TB among children globally. We did a systematic review and meta-analysis of observational studies reporting DR-TB among children by searching Embase, PubMed, and Scopus databases from January 1, 2000 to October 1, 2020. Publications reporting more than 60 children with bacteriological confirmed tuberculosis and phenotypical drug susceptibility testing (DST) results were included. Pooled proportions of MDR-TB and sub-analysis by age subgroups, regions, economical levels were performed. We identified 4,063 studies, of which 37 were included. Of 23,652 pediatric TB patients, the proportions of DR-TB, MDR-TB, mono-resistant TB, polydrug resistant TB, extensively drug-resistant TB were 13.59% (1,964/14,453), 3.72% (881/23,652), 6.07% (529/8,719), 1.61% (119/7,361), 0.44% (30/6,763), respectively. The pooled proportion of MDR-TB among 23,652 children of 37 studies was 3.7% (95% CI, 3.5-4.0%). Rate of MDR-TB was much lower in high-income countries (1.8%) than that in lower-middle-income countries (6.3%) and upper-middle-income countries (7.3%). More specifically, the rates of MDR-TB were 1.7% in USA, 1.7% in UK, 2.9% in India, 6.0% in South Africa, 9.8% in China, respectively. The burden of DR-TB remains high in children, and there are potential associations between rates of pediatric MDR-TB and national economical levels. More interventions on child TB cases in low-income countries may be urgently needed in future.
Topics: Antitubercular Agents; Child; Extensively Drug-Resistant Tuberculosis; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 34490197
DOI: 10.3389/fpubh.2021.721817 -
PloS One 2013In 2011, World Health Organization revised its recommendation for microbiological monitoring during treatment for multidrug-resistant tuberculosis (MDR-TB) by increasing... (Review)
Review
BACKGROUND
In 2011, World Health Organization revised its recommendation for microbiological monitoring during treatment for multidrug-resistant tuberculosis (MDR-TB) by increasing the frequency of culture examination from quarterly to monthly after culture conversion. Implementing the recommendation requires substantial additional investment in laboratory infrastructure. The objective of this review is to provide cost evidence that is needed for national TB programs to budget for optimal monitoring strategies.
METHODS AND FINDINGS
WE CONDUCTED THE FIRST SYSTEMATIC LITERATURE REVIEW ON UNIT COST ESTIMATES OF THREE MONITORING STRATEGIES: 1) smear only; 2) culture only; 3) combined smear and culture. 26 peer-reviewed studies were selected by searching 10 databases in English and Chinese for literature published between 1995 and 2012. Cost estimates were converted into 2010 constant USD and international dollars. We assessed the quality of the estimates using a matrix with five essential elements and provided a cost projection for the combined smear and culture tests where the data were available. The 26 studies reported the cost estimates in 16 predominantly high- or middle-income countries from 1993 to 2009. The estimated unit cost for smear, culture, and combined tests ranges from $0.26 to $10.50, $1.63 to $62.01, and $26.73 to $39.57, respectively. The ratio of culture to smear costs varies from 1.35 to 11.98. The wide range of estimates is likely attributable to using different laboratory methods in different regions and years and differing practices in collecting and reporting cost data. Most studies did not report information critical for generalizing their conclusions.
CONCLUSION
The paucity and low quality of unit cost estimates for TB monitoring in resource-poor settings impose technical challenges in predicting the resources needed for strengthening microbiological monitoring. To improve the validity and comparability of the cost data, we strongly advocate the data collection, estimation, and reporting follow protocols proposed by WHO.
Topics: Antitubercular Agents; Bacteriological Techniques; Cost-Benefit Analysis; Humans; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant; World Health Organization
PubMed: 23457502
DOI: 10.1371/journal.pone.0056074 -
PLoS Neglected Tropical Diseases Jan 2018Mycobacterium bovis (M. bovis) is the main causative agent of bovine zoonotic tuberculosis. The aim of this systematic review is to highlight the occupational exposure... (Review)
Review
BACKGROUND
Mycobacterium bovis (M. bovis) is the main causative agent of bovine zoonotic tuberculosis. The aim of this systematic review is to highlight the occupational exposure to bovine tuberculosis due to M. bovis.
METHODOLOGY/PRINCIPAL FINDINGS
A computer based literature search was carried out to identify papers published between January 2006 and March 2017. "PubMed, Cochrane Library and Science Direct" databases were searched systematically. Articles presenting the following properties were included: (i) focusing on M. bovis; (ii) concerning occupational exposure to bovine tuberculosis. A quality assessment was performed after selection of studies. Our search strategy identified a total of 3,264 papers of which 29 studies met the inclusion criteria. Of the 29 articles, 17 were cross-sectional studies (6 were of high quality and scored in the range of 6-7, 11 were of moderate quality and scored in the range 3-5), 10 were case reports, and 2 were reviews. Different occupational fields exposing to the disease were described: livestock sector, particularly in contact with dairy cattle (farmers, veterinaries and assistants, abattoir workers) and working in contact with wildlife (hunters, taxidermists).
CONCLUSIONS
A specific guideline for occupational practitioners taking care of employees exposed to bovine tuberculosis is warranted and should be tailored to level of exposure. This review was intended to be the first step of such a project. Articles were identified from various continents and countries with different socio-economic situations, broadening our understanding of the worldwide situation. Published data on occupational exposure in developed countries are scarce. We had to extrapolate findings from countries with higher prevalence of the disease.
Topics: Animals; Cattle; Cross-Sectional Studies; Humans; Mycobacterium bovis; Occupational Exposure; Tuberculosis
PubMed: 29337996
DOI: 10.1371/journal.pntd.0006208 -
Tuberculosis (Edinburgh, Scotland) May 2020Diagnosing tuberculous pleurisy (TP) remains a clinical challenge and the best method to diagnose it is controversial. Although several studies have investigated the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diagnosing tuberculous pleurisy (TP) remains a clinical challenge and the best method to diagnose it is controversial. Although several studies have investigated the performance of pleural fluid (PF) T-SPOT for pleural tuberculosis (plTB) diagnosis, the heterogeneity of its accuracy exists. Therefore, we performed an updated meta-analysis of the existing evidence on the utility of PF T-SPOT to diagnose TP.
METHODS
PubMed and EmBase were searched for relevant English articles up to July 29, 2019. Statistical analysis was performed using Stata, Revman, and Meta-Disc. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were determined. Summary receiver operating characteristic (SROC) curves and the area under the curve (AUC) were used to summarize the overall diagnostic performance.
RESULTS
A total of 13 studies (997 patients with TP and 656 patients without TP) were identified and enrolled to meta-analysis, giving the following pooled values for diagnostic accuracy of PF T-SPOT: sensitivity, 0.91 (95% CI, 0.89-0.92, I = 80.9%); specificity, 0.88 (95% CI, 0.86-0.91, I = 87.3%); PLR, 6.28 (95% CI, 2.88-13.69, I = 93.3%); NLR, 0.12 (95% CI, 0.07-0.21, I = 84.9%); DOR, 59.74 (95% CI, 24.13-147.93, I = 78.3%); and the area under the SROC curve, 0.95 (95% CI, 0.93-0.97).
CONCLUSIONS
Our meta-analysis suggests that PF T-SPOT has important diagnostic value for plTB. However, the standardization of the operating procedure needs to be further promoted, which would make the results more credible.
Topics: Host-Pathogen Interactions; Humans; Interferon-gamma; Interferon-gamma Release Tests; Mycobacterium tuberculosis; Predictive Value of Tests; Reproducibility of Results; Tuberculosis, Pleural
PubMed: 32501259
DOI: 10.1016/j.tube.2020.101941 -
PloS One 2015The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to... (Review)
Review
Frequency and geographic distribution of gyrA and gyrB mutations associated with fluoroquinolone resistance in clinical Mycobacterium tuberculosis isolates: a systematic review.
BACKGROUND
The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to fluoroquinolones is the most promising technology for rapid diagnosis of fluoroquinolone resistance.
METHODS
In order to characterize the diversity and frequency of gyrA and gyrB mutations and to describe the global distribution of these mutations, we conducted a systematic review, from May 1996 to April 2013, of all published studies evaluating Mycobacterium tuberculosis mutations associated with resistance to fluoroquinolones. The overall goal of the study was to determine the potential utility and reliability of these mutations as diagnostic markers to detect phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis and to describe their geographic distribution.
RESULTS
Forty-six studies, covering four continents and 18 countries, provided mutation data for 3,846 unique clinical isolates with phenotypic resistance profiles to fluoroquinolones. The gyrA mutations occurring most frequently in fluoroquinolone-resistant isolates, ranged from 21-32% for D94G and 13-20% for A90V, by drug. Eighty seven percent of all strains that were phenotypically resistant to moxifloxacin and 83% of ofloxacin resistant isolates contained mutations in gyrA. Additionally we found that 83% and 80% of moxifloxacin and ofloxacin resistant strains respectively, were observed to have mutations in the gyrA codons interrogated by the existing MTBDRsl line probe assay. In China and Russia, 83% and 84% of fluoroquinolone resistant strains respectively, were observed to have gyrA mutations in the gene regions covered by the MTBDRsl assay.
CONCLUSIONS
Molecular diagnostics, specifically the Genotype MTBDRsl assay, focusing on codons 88-94 should have moderate to high sensitivity in most countries. While we did observe geographic differences in the frequencies of single gyrA mutations across countries, molecular diagnostics based on detection of all gyrA mutations demonstrated to confer resistance should have broad and global utility.
Topics: Anti-Bacterial Agents; DNA Gyrase; Drug Resistance, Bacterial; Fluoroquinolones; Humans; Meta-Analysis as Topic; Mutation; Mycobacterium tuberculosis; Tuberculosis, Pulmonary
PubMed: 25816236
DOI: 10.1371/journal.pone.0120470