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The Pediatric Infectious Disease Journal May 2013Isoniazid resistance is an obstacle to the treatment of tuberculosis disease and latent tuberculosis infection in children. We aim to summarize the literature describing... (Review)
Review
BACKGROUND
Isoniazid resistance is an obstacle to the treatment of tuberculosis disease and latent tuberculosis infection in children. We aim to summarize the literature describing the risk of isoniazid-resistant tuberculosis among children with tuberculosis disease.
METHODS
We did a systematic review of published reports of children with tuberculosis disease who had isolates tested for susceptibility to isoniazid. We searched PubMed, Embase and LILACS online databases up to January 12, 2012.
RESULTS
Our search identified 3403 citations, of which 95 studies met inclusion criteria. These studies evaluated 8351 children with tuberculosis disease for resistance to isoniazid. The median proportion of children found to have isoniazid-resistant strains was 8%; the distribution was right-skewed (25th percentile: 0% and 75th percentile: 18%).
CONCLUSIONS
High proportions of isoniazid resistance among pediatric tuberculosis patients have been reported in many settings suggesting that diagnostics detecting only rifampin resistance are insufficient to guide appropriate treatment in this population. Many children are likely receiving substandard tuberculosis treatment with empirical isoniazid-based regimens, and treating latent tuberculosis infection with isoniazid may not be effective in large numbers of children. Work is needed urgently to identify effective regimens for the treatment of children sick with or exposed to isoniazid-resistant tuberculosis and to better understand the scope of this problem.
Topics: Adolescent; Antitubercular Agents; Child; Child, Preschool; Drug Resistance, Bacterial; Humans; Infant; Isoniazid; Mycobacterium tuberculosis; Tuberculosis
PubMed: 23348808
DOI: 10.1097/INF.0b013e3182865409 -
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 -
PLoS Neglected Tropical Diseases Dec 2010Buruli ulcer is a neglected emerging disease that has recently been reported in some countries as the second most frequent mycobacterial disease in humans after... (Review)
Review
Buruli ulcer is a neglected emerging disease that has recently been reported in some countries as the second most frequent mycobacterial disease in humans after tuberculosis. Cases have been reported from at least 32 countries in Africa (mainly west), Australia, Southeast Asia, China, Central and South America, and the Western Pacific. Large lesions often result in scarring, contractual deformities, amputations, and disabilities, and in Africa, most cases of the disease occur in children between the ages of 4-15 years. This environmental mycobacterium, Mycobacterium ulcerans, is found in communities associated with rivers, swamps, wetlands, and human-linked changes in the aquatic environment, particularly those created as a result of environmental disturbance such as deforestation, dam construction, and agriculture. Buruli ulcer disease is often referred to as the "mysterious disease" because the mode of transmission remains unclear, although several hypotheses have been proposed. The above review reveals that various routes of transmission may occur, varying amongst epidemiological setting and geographic region, and that there may be some role for living agents as reservoirs and as vectors of M. ulcerans, in particular aquatic insects, adult mosquitoes or other biting arthropods. We discuss traditional and non-traditional methods for indicting the roles of living agents as biologically significant reservoirs and/or vectors of pathogens, and suggest an intellectual framework for establishing criteria for transmission. The application of these criteria to the transmission of M. ulcerans presents a significant challenge.
Topics: Age Factors; Animals; Buruli Ulcer; Communicable Diseases, Emerging; Disease Reservoirs; Disease Vectors; Ecosystem; Environmental Microbiology; Humans; Mycobacterium ulcerans
PubMed: 21179505
DOI: 10.1371/journal.pntd.0000911 -
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 -
Journal of Clinical Microbiology Apr 2016A systematic review investigating the role of Xpert MTB/RIF in the diagnosis of tuberculous pleural effusion (TPE) was conducted. The pooled sensitivities and... (Meta-Analysis)
Meta-Analysis Review
A systematic review investigating the role of Xpert MTB/RIF in the diagnosis of tuberculous pleural effusion (TPE) was conducted. The pooled sensitivities and specificities of Xpert MTB/RIF were 51.4% and 98.6%, respectively, with culture used as a reference standard and 22.7% and 99.8%, respectively, with a composite reference standard (CRS) used as the benchmark. Xpert MTB/RIF has low sensitivity but excellent specificity in the diagnosis of TPE.
Topics: Antitubercular Agents; Drug Resistance, Bacterial; Humans; Molecular Diagnostic Techniques; Mycobacterium tuberculosis; Pleural Effusion; Rifampin; Sensitivity and Specificity; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pleural
PubMed: 26818675
DOI: 10.1128/JCM.03205-15 -
Clinical Infectious Diseases : An... Jun 2023We compared 6 new interferon-γ release assays (IGRAs; hereafter index tests: QFT-Plus, QFT-Plus CLIA, QIAreach, Wantai TB-IGRA, Standard E TB-Feron, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We compared 6 new interferon-γ release assays (IGRAs; hereafter index tests: QFT-Plus, QFT-Plus CLIA, QIAreach, Wantai TB-IGRA, Standard E TB-Feron, and T-SPOT.TB/T-Cell Select) with World Health Organization (WHO)-endorsed tests for tuberculosis infection (hereafter reference tests).
METHODS
Data sources (1 January 2007-18 August 2021) were Medline, Embase, Web of Science, Cochrane Database of Systematic Reviews, and manufacturers' data. Cross-sectional and cohort studies comparing the diagnostic performance of index and reference tests were selected. The primary outcomes of interest were the pooled differences in sensitivity and specificity between index and reference tests. The certainty of evidence (CoE) was summarized using the GRADE approach.
RESULTS
Eighty-seven studies were included (44 evaluated the QFT-Plus, 4 QFT-Plus CLIA, 3 QIAreach, 26 TB-IGRA, 10 TB-Feron [1 assessing the QFT-Plus], and 1 T-SPOT.TB/T-Cell Select). Compared to the QFT-GIT, QFT Plus's sensitivity was 0.1 percentage points lower (95% confidence interval [CI], -2.8 to 2.6; CoE: moderate), and its specificity 0.9 percentage points lower (95% CI, -1.0 to -.9; CoE: moderate). Compared to QFT-GIT, TB-IGRA's sensitivity was 3.0 percentage points higher (95% CI, -.2 to 6.2; CoE: very low), and its specificity 2.6 percentage points lower (95% CI, -4.2 to -1.0; CoE: low). Agreement between the QFT-Plus CLIA and QIAreach with QFT-Plus was excellent (pooled κ statistics of 0.86 [95% CI, .78 to .94; CoE: low]; and 0.96 [95% CI, .92 to 1.00; CoE: low], respectively). The pooled κ statistic comparing the TB-Feron and the QFT-Plus or QFT-GIT was 0.85 (95% CI, .79 to .92; CoE: low).
CONCLUSIONS
The QFT-Plus and the TB-IGRA have very similar sensitivity and specificity as WHO-approved IGRAs.
Topics: Humans; Interferon-gamma Release Tests; Cross-Sectional Studies; Tuberculosis; Latent Tuberculosis; Sensitivity and Specificity; Tuberculin Test; Mycobacterium tuberculosis
PubMed: 36688489
DOI: 10.1093/cid/ciad030 -
BMC Infectious Diseases Dec 2022Countries with high TB burden have expanded access to molecular diagnostic tests. However, their impact on reducing delays in TB diagnosis and treatment has not been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Countries with high TB burden have expanded access to molecular diagnostic tests. However, their impact on reducing delays in TB diagnosis and treatment has not been assessed. Our primary aim was to summarize the quantitative evidence on the impact of nucleic acid amplification tests (NAAT) on diagnostic and treatment delays compared to that of the standard of care for drug-sensitive and drug-resistant tuberculosis (DS-TB and DR-TB).
METHODS
We searched MEDLINE, EMBASE, Web of Science, and the Global Health databases (from their inception to October 12, 2020) and extracted time delay data for each test. We then analysed the diagnostic and treatment initiation delay separately for DS-TB and DR-TB by comparing smear vs Xpert for DS-TB and culture drug sensitivity testing (DST) vs line probe assay (LPA) for DR-TB. We conducted random effects meta-analyses of differences of the medians to quantify the difference in diagnostic and treatment initiation delay, and we investigated heterogeneity in effect estimates based on the period the test was used in, empiric treatment rate, HIV prevalence, healthcare level, and study design. We also evaluated methodological differences in assessing time delays.
RESULTS
A total of 45 studies were included in this review (DS = 26; DR = 20). We found considerable heterogeneity in the definition and reporting of time delays across the studies. For DS-TB, the use of Xpert reduced diagnostic delay by 1.79 days (95% CI - 0.27 to 3.85) and treatment initiation delay by 2.55 days (95% CI 0.54-4.56) in comparison to sputum microscopy. For DR-TB, use of LPAs reduced diagnostic delay by 40.09 days (95% CI 26.82-53.37) and treatment initiation delay by 45.32 days (95% CI 30.27-60.37) in comparison to any culture DST methods.
CONCLUSIONS
Our findings indicate that the use of World Health Organization recommended diagnostics for TB reduced delays in diagnosing and initiating TB treatment. Future studies evaluating performance and impact of diagnostics should consider reporting time delay estimates based on the standardized reporting framework.
Topics: Humans; Rifampin; Tuberculosis, Pulmonary; Mycobacterium tuberculosis; Delayed Diagnosis; Time-to-Treatment; Pathology, Molecular; Sensitivity and Specificity; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 36517736
DOI: 10.1186/s12879-022-07855-9 -
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 -
Tuberculosis (Edinburgh, Scotland) Jan 2021Tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are currently the two main causes of death among infectious diseases. There is an increasing number of studies...
Tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are currently the two main causes of death among infectious diseases. There is an increasing number of studies trying to elucidate the interactions between Mycobacterium tuberculosis and SARS-CoV-2. Some of the first case reports point to a worsening of respiratory symptoms in co-infected TB/COVID-19 individuals. However, data from the cohort studies has shown some conflicting results. This study proposes to conduct a systematic review on the current literature on TB/COVID-19 co-infection cohorts, evaluating clinical and epidemiological data, focusing on its implications to the immune system. From an immunological perspective, the TB/COVID-19 co-infection has the potential to converge in a "perfect storm". The disorders induced by each pathogen to the immunomodulation tend to induce an unbalanced inflammatory response, which can promote the progression and worsening of both diseases. Understanding the nature of the interactions between M. tuberculosis and SARS-CoV-2 will be crucial for the development of therapeutic strategies against co-infection.
Topics: Animals; COVID-19; Coinfection; Disease Progression; Host-Pathogen Interactions; Humans; Inflammation Mediators; Lung; Mycobacterium tuberculosis; Prognosis; SARS-CoV-2; Signal Transduction; Tuberculosis, Pulmonary
PubMed: 33246269
DOI: 10.1016/j.tube.2020.102020 -
BMC Medicine Mar 2016Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions... (Review)
Review
BACKGROUND
Whole genome sequencing (WGS) is becoming an important part of epidemiological investigations of infectious diseases due to greater resolution and cost reductions compared to traditional typing approaches. Many public health and clinical teams will increasingly use WGS to investigate clusters of potential pathogen transmission, making it crucial to understand the benefits and assumptions of the analytical methods for investigating the data. We aimed to understand how different approaches affect inferences of transmission dynamics and outline limitations of the methods.
METHODS
We comprehensively searched electronic databases for studies that presented methods used to interpret WGS data for investigating tuberculosis (TB) transmission. Two authors independently selected studies for inclusion and extracted data. Due to considerable methodological heterogeneity between studies, we present summary data with accompanying narrative synthesis rather than pooled analyses.
RESULTS
Twenty-five studies met our inclusion criteria. Despite the range of interpretation tools, the usefulness of WGS data in understanding TB transmission often depends on the amount of genetic diversity in the setting. Where diversity is small, distinguishing re-infections from relapses may be impossible; interpretation may be aided by the use of epidemiological data, examining minor variants and deep sequencing. Conversely, when within-host diversity is large, due to genetic hitchhiking or co-infection of two dissimilar strains, it is critical to understand how it arose. Greater understanding of microevolution and mixed infection will enhance interpretation of WGS data.
CONCLUSIONS
As sequencing studies have sampled more intensely and integrated multiple sources of information, the understanding of TB transmission and diversity has grown, but there is still much to be learnt about the origins of diversity that will affect inferences from these data. Public health teams and researchers should combine epidemiological, clinical and WGS data to strengthen investigations of transmission.
Topics: Bacterial Typing Techniques; Genetic Variation; Genome, Bacterial; Genome-Wide Association Study; Humans; Mycobacterium tuberculosis; Recurrence; Sequence Analysis, DNA; Tuberculosis
PubMed: 27005433
DOI: 10.1186/s12916-016-0566-x