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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 -
Frontiers in Immunology 2022The early diagnosis of tuberculosis using novel non-sputum-based biomarkers is of high priority in the End TB strategy. MicroRNAs (miRNAs) are significant regulators of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The early diagnosis of tuberculosis using novel non-sputum-based biomarkers is of high priority in the End TB strategy. MicroRNAs (miRNAs) are significant regulators of TB pathogenesis and their differential expression pattern among healthy, latent, and active TB population has revealed their potentiality as biomarkers in recent studies. Thus, we systematically reviewed and performed a meta-analysis on the role of host miRNAs in TB diagnosis. We also reviewed the involvement of miRNAs in the immune response to ().
METHODS
Pubmed, Ovid and Cochrane databases were searched to retrieve published literature from 2000 to 2020 using predefined keywords. We screened relevant studies based on inclusion and exclusion criteria and the included studies were assessed for their quality using STARD guidelines and QUADAS-2 tool. Funnel plots were constructed to assess the publication bias. The heterogeneity of studies and overall pooled results of sensitivity, specificity and DOR were determined using forest plots.
RESULTS
We retrieved a total of 447 studies collectively from all the databases, out of which 21 studies were included for qualitative analysis. In these studies, miR-29, miR-31, miR-125b, miR146a and miR-155 were consistently reported. The overall sensitivity, specificity and DOR of these miRNAs were found to be 87.9% (81.7-92.2), 81.2% (74.5-86.5) and 43.1(20.3-91.3) respectively. Among these, miR-31 had the maximum diagnostic accuracy, with a sensitivity of 96% (89.7-98.5), specificity of 89% (81.2-93.8) and DOR of 345.9 (90.2-1326.3), meeting the minimal target product profile (TPP) for TB diagnostics.
CONCLUSION
miRNAs can thus be exploited as potential biomarkers for rapid detection of tuberculosis as evident from their diagnostic performance.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021226559 PROSPERO (CRD42021226559).
Topics: Biomarkers; Humans; MicroRNAs; Mycobacterium tuberculosis; Tuberculosis
PubMed: 36238288
DOI: 10.3389/fimmu.2022.954396 -
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 -
International Journal of Infectious... Nov 2022We aimed to investigate published data on treatment outcomes of multidrug-resistant (MDR)/rifampicin-resistant tuberculosis (TB) in Central and West Africa because... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We aimed to investigate published data on treatment outcomes of multidrug-resistant (MDR)/rifampicin-resistant tuberculosis (TB) in Central and West Africa because these, to the best of our knowledge, are sparsely available.
METHODS
Systematic review and meta-analysis.
RESULTS
A total of 14 studies were included, representing 4268 individuals in 14 of the 26 countries. Using a random-effects model meta-analysis, we observed a pooled success rate of 80.8% (95% confidence interval [CI] 56.0-93.3) for the Central African subgroup and 69.2% (95% CI 56.3-79.7) for the West African subgroup (P = 0.0522). The overall treatment success for all studies was 74.6% (95% CI 65.0-82.2). We found high heterogeneity among included studies (I = 96.1%). The estimated proportion of successfully treated individuals with MDR/rifampicin-resistant TB was considerably higher than the global estimate provided by the World Health Organization (59%), reaching the 2015 World Health Organization target of at least 75% treatment success for MDR-TB.
CONCLUSION
The use of shorter treatment regimens and the standardized treatment conditions, including directly observed therapy in these studies, could have contributed to a high treatment success. Yet, the available literature was not fully representative of the regions, possibly highlighting the sparse resources in many of these countries. The review was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42022353163).
Topics: Humans; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Rifampin; Directly Observed Therapy; Treatment Outcome; Mycobacterium tuberculosis
PubMed: 36007688
DOI: 10.1016/j.ijid.2022.08.015 -
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 -
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 -
Scientific Reports Jan 2021In Sub-Saharan Africa, African giant pouched rats (Cricetomys gambianus) are trained to identify TB patients by smelling sputum. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
In Sub-Saharan Africa, African giant pouched rats (Cricetomys gambianus) are trained to identify TB patients by smelling sputum. We conducted a systematic review and meta-analysis of the data to see if this novel method is comparable to traditional laboratory screening and detection methods like Ziehl-Neelsen stain-based assays (ZN) and bacterial culture. The search and data processing strategy is registered at PROSPERO (CRD42019123629). Medline via PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically searched for the keywords "pouched rat" and "tuberculosis". Data from 53,181 samples obtained from 24,600 patients were extracted from seven studies. Using sample-wise detection, the sensitivity of the studies was 86.7% [95% CI 80.4-91.2%], while the specificity was 88.4% [95% CI 79.7-93.7%]. For patient-wise detection, the sensitivity was 81.3% [95% CI 64.0-91.4%], while the specificity was 73.4% [95% CI 62.8-81.9%]. Good and excellent classification was assessed by hierarchical summary receiver-operating characteristic analysis for patient-wise and sample-wise detections, respectively. Our study is the first systematic review and meta-analysis of the above relatively inexpensive and rapid screening method. The results indicate that African giant pouched rats can discriminate healthy controls from TB individuals by sniffing sputum with even a higher accuracy than a single ZN screening.
Topics: Animals; Clinical Laboratory Techniques; Humans; Mycobacterium tuberculosis; Reproducibility of Results; Rodentia; Sensitivity and Specificity; Smell; Sputum; Tuberculosis, Pulmonary
PubMed: 33479276
DOI: 10.1038/s41598-021-81086-x -
Frontiers in Public Health 2020China is a high-burden country of tuberculosis. The proportion of diseases caused by non-tuberculous mycobacteria (NTM) has increased, seriously affecting the... (Meta-Analysis)
Meta-Analysis
China is a high-burden country of tuberculosis. The proportion of diseases caused by non-tuberculous mycobacteria (NTM) has increased, seriously affecting the prevention, control, and management of tuberculosis (TB) and posing a significant threat to human health. However, there is a lack of an organized monitoring system for NTM such as that used for tuberculosis. Comprehensive data on patient susceptibility, dominant species, and drug resistance profiles are needed to improve the treatment protocols and the management of NTM. Primary research reports of NTM clinical specimens from mainland China published between January 1, 2000 and May 31, 2019 were retrieved from four online resources (BIOSIS, Embase, PubMed, and Web of Science) and three Chinese medical literature databases (CNKI, Wanfang, and Vip) as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. In total, 339 publications were included in the systematic review, 129 were used in the drug susceptibility analysis, and 95 were used in the meta-analysis. Traditional culture using Lowenstein-Jensen slants combined with P-nitrobenzene acid and thiophene-2-carboxylic acid hydrazine differential medium and proportional method was most commonly used for the isolation, identification, and drug susceptibility testing of NTM in China. The crude isolation rate for NTM among TB suspected cases was 4.66-5.78%, while the proportion of NTM among isolates was 11.57%. and complex were the most common clinical NTM species. NTM only showed general sensitivity to ethambutol, linezolid, clofazimine, amikacin, tobramycin, and clarithromycin. The prevalence of NTM in China has shown a decreasing trend. was replaced as the dominant species by over the course of the study. The geographic diversity of different species showed the effects of environmental and economic factors on the distribution of NTM and indicated that there were important factors still not identified. While there were only a limited number of antibiotics to which NTM showed any sensitivity, the drug resistance profiles of the isolates were highly variable and thus more caution should be taken when empirically treating NTM infection.
Topics: China; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Prevalence
PubMed: 32850570
DOI: 10.3389/fpubh.2020.00295 -
The Lancet. Microbe Nov 2021Bedaquiline is a crucial drug for control of rifampicin-resistant tuberculosis. Molecular drug resistance assays could facilitate effective use of bedaquiline and...
BACKGROUND
Bedaquiline is a crucial drug for control of rifampicin-resistant tuberculosis. Molecular drug resistance assays could facilitate effective use of bedaquiline and surveillance of drug resistance emergence. To facilitate molecular assay development, we aimed to identify genomic markers of bedaquiline resistance.
METHODS
In this systematic review and individual isolate analysis, we searched Europe PubMed Central and Scopus for studies published from the inception of each database until Oct 19, 2020, that assessed genotypic and phenotypic bedaquiline resistance in clinical or non-clinical isolates. All studies reporting on the assessment of variants in the four genes of interest (, , , and ) and phenotypic bedaquiline data in both clinical and non-clinical samples were included. We collated individual isolate data from eligible studies to assess the association between genomic variants with phenotypic bedaquiline resistance, using a standardised method endorsed by WHO. Risk of bias of the extracted data was independently assessed by two authors using the Quality Assessment of Diagnostic Accuracy Studies tool for clinical studies and Systematic Review Center for Laboratory Animal Experimentation tool for animal studies. The primary outcome was to identify mutations associated with resistance in four genes of interest (, , , and ); for each genomic variant, the odds ratio (OR), 95% CI, and p value were calculated to identify resistance markers associated with bedaquiline resistance. This study is registered with PROSPERO, CRD42020221498.
FINDINGS
Of 1367 studies identified, 41 published between 2007 and 2020 were eligible for inclusion. We extracted data on 1708 isolates: 1569 (91·9%) clinical isolates and 139 (8·1%) non-clinical isolates. We identified 237 unique variants in , 14 in , 28 in and 11 in . Most clinical isolates with a single variant reported in (229 [79%] of 287 variants), (14 [88%] of 16 variants), (32 [100%] of 32 variants), or (115 [98%] of 119 variants) were phenotypically susceptible to bedaquiline. Except for the 187G→C (OR ∞, [95% CI 13·28-∞]; p<0·0001) and 138_139insG (OR 6·91 [95% CI 1·16-47·38]; p=0·016) variants, phenotypic-genotypic associations were not significant (p≥0·05) for any single variant in , , and .
INTERPRETATION
Absence of clear genotypic-phenotypic associations for bedaquiline complicates the development of molecular drug susceptibility tests. A concerted global effort is urgently needed to assess the genotypic and phenotypic drug susceptibility of isolates, especially in patients who have received unsuccessful bedaquiline-containing regimens. Treatment regimens should be designed to prevent emergence of bedaquiline resistance and phenotypic drug susceptibility tests should be used to guide and monitor treatment.
FUNDING
Research Foundation Flanders, South African Medical Research Council, Department of Science and Innovation - National Research Foundation, National Institute of Health Institute of Allergy and Infectious Diseases, and Doris Duke Charitable Foundation.
Topics: Animals; Antitubercular Agents; Data Analysis; Diarylquinolines; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Tuberculosis, Lymph Node; Tuberculosis, Multidrug-Resistant
PubMed: 34796339
DOI: 10.1016/s2666-5247(21)00175-0 -
International Journal of Environmental... Jan 2023The widespread paradigm that younger children usually do not transmit complex (Mtbc) to their contacts has not yet been proven by genotypically confirmed transmissions.... (Review)
Review
The widespread paradigm that younger children usually do not transmit complex (Mtbc) to their contacts has not yet been proven by genotypically confirmed transmissions. Therefore, we undertook a systematic review of molecular-epidemiological studies to investigate documented source and secondary TB (tuberculosis) cases among children. We searched the literature published before August 2022 using , , and databases. PRISMA statement was used for systematic review. Of 312 records retrieved, 39 studies including children aged below 15 years offered epidemiological links between cluster members. In the 39 studies from 16 countries, 225 children were reported as cluster members of whom the overwhelming majority were infected by adults. Only 3 children-of those were 2 children aged below 10-were reported to be the definite source cases of 11 other children and 1 adult with genotypically matched Mtbc isolates. To date, molecular-epidemiological studies involving children with verified transmission links are scarce. As far as the heterogeneity of the studies we identified allows, we could conclude that the results confirm the paradigm that children aged below 10 hardly ever transmit Mtbc to others. The true extent of TB transmission through children may, however, be underestimated by those selected studies.
Topics: Adult; Humans; Child; Mycobacterium tuberculosis; Tuberculosis; Molecular Epidemiology; Epidemiologic Studies; Only Child
PubMed: 36767111
DOI: 10.3390/ijerph20031737