Publications
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Abubakar I, Lalvani A, Southern J, et al., 2018, Two interferon gamma release assays for predicting active tuberculosis: the UK PREDICT TB prognostic test study, Health Technology Assessment, Vol: 22, Pages: 1-95, ISSN: 1366-5278
BACKGROUND: Despite a recent decline in the annual incidence of tuberculosis (TB) in the UK, rates remain higher than in most Western European countries. The detection and treatment of latent TB infection (LTBI) is an essential component of the UK TB control programme. OBJECTIVES: To assess the prognostic value and cost-effectiveness of the current two interferon gamma release assays (IGRAs) compared with the standard tuberculin skin test (TST) for predicting active TB among untreated individuals at increased risk of TB: (1) contacts of active TB cases and (2) new entrants to the UK from high-TB-burden countries. DESIGN: A prospective cohort study and economic analysis. PARTICIPANTS AND SETTING: Participants were recruited in TB clinics, general practices and community settings. Contacts of active TB cases and migrants who were born in high-TB-burden countries arriving in the UK were eligible to take part if they were aged ≥ 16 years. MAIN OUTCOME MEASURES: Outcomes include incidence rate ratios comparing the incidence of active TB in those participants with a positive test result and those with a negative test result for each assay, and combination of tests and the cost per quality-adjusted life-year (QALY) for each screening strategy. RESULTS: A total of 10,045 participants were recruited between May 2010 and July 2015. Among 9610 evaluable participants, 97 (1.0%) developed active TB. For the primary analysis, all test data were available for 6380 participants, with 77 participants developing active TB. A positive result for TSTa (positive if induration is ≥ 5 mm) was a significantly poorer predictor of progression to active TB than a positive result for any of the other tests. Compared with TSTb [positive if induration is ≥ 6 mm without prior bacillus Calmette-Guérin (BCG) alone, T-SPOT®.TB (Oxford Immunotec Ltd, Oxford, UK), TSTa + T-SPOT.TB, TSTa + IGRA and the three combination
Broda A, Nikolayevskyy V, Casali N, et al., 2018, Experimental platform utilising melting curve technology for detection of mutations in Mycobacterium tuberculosis isolates, European Journal of Clinical Microbiology and Infectious Diseases, Vol: 37, Pages: 1273-1279, ISSN: 0934-9723
Tuberculosis (TB) remains one of the most deadly infections with approximately a quarter of cases not being identified and/or treated mainly due to a lack of resources. Rapid detection of TB or drug-resistant TB enables timely adequate treatment and is a cornerstone of effective TB management. We evaluated the analytical performance of a single-tube assay for multidrug-resistant TB (MDR-TB) on an experimental platform utilising RT-PCR and melting curve analysis that could potentially be operated as a point-of-care (PoC) test in resource-constrained settings with a high burden of TB. Firstly, we developed and evaluated the prototype MDR-TB assay using specimens extracted from well-characterised TB isolates with a variety of distinct rifampicin and isoniazid resistance conferring mutations and nontuberculous Mycobacteria (NTM) strains. Secondly, we validated the experimental platform using 98 clinical sputum samples from pulmonary TB patients collected in high MDR-TB settings. The sensitivity of the platform for TB detection in clinical specimens was 75% for smear-negative and 92.6% for smear-positive sputum samples. The sensitivity of detection for rifampicin and isoniazid resistance was 88.9 and 96.0% and specificity was 87.5 and 100%, respectively. Observed limitations in sensitivity and specificity could be resolved by adjusting the sample preparation methodology and melting curve recognition algorithm. Overall technology could be considered a promising PoC methodology especially in resource-constrained settings based on its combined accuracy, convenience, simplicity, speed, and cost characteristics.
Lalor MK, Casali N, Walker TM, et al., 2018, The use of whole-genome sequencing in cluster investigation of an MDR-TB outbreak, European Respiratory Journal, Vol: 51, ISSN: 0903-1936
We used whole-genome sequencing to delineate transmission networks and investigate the benefits of whole-genome sequencing during cluster investigation.We included clustered cases of M/XDR-TB linked by MIRU-VNTR, or epidemiological information in the national cluster B1006, notified between 2007-2013 in the UK. We excluded cases whose isolates differed by >12 SNPs from further investigation. Data relating to patients’ social networks were collected.Twenty-seven cases were investigated, 22 had whole-genome sequencing; 8 (36%) of which were excluded as their isolates differed by >12 SNPs to other cases. Eighteen cases were ruled into the transmission network based on genomic and epidemiological information. Evidence of transmission was inconclusive in 39% (7/18) of cases in the transmission network following whole-genome sequencing and epidemiological investigation. This investigation of a drug resistant TB cluster illustrates the opportunities and limitations of whole-genome sequencing in understanding transmission in a setting with a high proportion of migrant cases. The use of WGS should be combined with classical epidemiological methods. However not every cluster will be solvable, regardless of the quality of genomic data.
Chongwe G, Michelo C, Sinkala E, et al., 2018, Mycobacterium avium lysate induces matrix metalloproteinase-1 in intestinal tissue and peripheral blood: observations from selected hospital based Zambian adults, International Journal of Infectious Diseases, Vol: 71, Pages: 73-81, ISSN: 1201-9712
OBJECTIVES: Environmental enteropathy is prevalent in low-income countries, although its aetiology is unknown. We investigated if Mycobacterium avium antigens, which are commonly found in the environment, could contribute to its pathogenesis in a population known to have widespread environmental enteropathy. METHODS: Routine endoscopy patients at the University Teaching Hospital, Lusaka whose endoscopy results were normal submitted duodenal biopsies and whole blood samples. Samples were stimulated with M. avium lysate over 24hours while unstimulated samples served as negative controls. Matrix metalloproteinase (MMP) and cytokine response in supernatants were quantified using ELISA and cytometric bead array. RESULTS: Samples from 48 patients (56% women) were analysed, with a median age of 35 years (IQR 27.5, 50.5). M. avium induced the secretion of a wide-range of Th1, Th2 and Th17 cytokines in blood but only IL-1β and IL-6 in duodenal tissue. However it differentially induced the secretion of MMP-1 in duodenal tissue compared to negative controls (p=0.004). A similar MMP-1 response but with lower concentrations was observed in blood. CONCLUSION: The induction of MMP-1 and cytokines by M. avium in duodenal tissue suggests that environmental mycobacteria could contribute to the epithelial disruption seen in environmental enteropathy, and a need to further explore possible biomarkers that may predict this exposure in at-risk populations.
Black AT, Hamblion EL, Buttivant H, et al., 2018, Tracking and responding to an outbreak of tuberculosis using MIRU-VNTR genotyping and whole genome sequencing as epidemiological tools, JOURNAL OF PUBLIC HEALTH, Vol: 40, Pages: E66-E73, ISSN: 1741-3842
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Vella V, Broda A, Drobniewski F, 2018, Should all suspected tuberculosis cases in high income countries be tested with GeneXpert?, Tuberculosis, Vol: 110, Pages: 112-120, ISSN: 1472-9792
In countries with a low incidence of multidrug-resistant tuberculosis (MDR-TB), universal testing with GeneXpert might not be always cost-effective. This study provides hospital managers in low MDR-TB incidence countries with criteria on when decentralised universal GeneXpert testing would make sense. The alternatives taken into consideration include: universal microbiological culture and drug susceptibility testing (DST) only (comparator); as above but with concurrent centralized GeneXpert in a referral laboratory vs a decentralized GeneXpert system in every hospital to test smear-positive cases only; as above but testing all samples with GeneXpert regardless of smear status. The parameters were from the national TB statistics for England and from a systematic review. Decentralised GeneXpert to test any suspected TB case was the most cost-effective option when 6% or more TB patients belonged to the high-risk group, defined as previous TB diagnosis and or being born in countries with a high MDR-TB incidence. Hospital managers in England and other low MDR-TB incidence countries could use these findings to decide when to invest in GeneXpert or other molecular diagnostics with similar performance criteria for TB diagnostics.
Drobniewski FA, Mathys V, Roycroft E, et al., 2018, Time-and-motion tool for the assessment of working time in tuberculosis laboratories: a multicentre study, International Journal of Tuberculosis and Lung Disease, Vol: 22, Pages: 444-451, ISSN: 1027-3719
SETTING: Implementation of novel diagnostic assays in tuberculosis (TB) laboratory diagnosis requires effective management of time and resources.OBJECTIVE: To further develop and assess at multiple centres a time-and-motion (T&M) tool as an objective means for recording the actual time spent on running laboratory assays.DESIGN: Multicentre prospective study conducted in six European Union (EU) reference TB laboratories.RESULTS: A total of 1060 specimens were tested using four laboratory assays. The number of specimens per batch varied from one to 60; a total of 64 recordings were performed. Theoretical hands-on times per specimen (TTPS) in h:min:s for Xpert® MTB/RIF, mycobacterial interspersed repetitive unit-variable number of tandem repeats genotyping, Ziehl-Neelsen staining and manual fluorescence microscopy were respectively 00:33:02 ± 00:12:32, 00:13:34 ± 00:03:11, 00:09:54 ± 00:00:53 and 00:06:23 ± 00:01:36. Variations between laboratories were predominantly linked to the time spent on reporting and administrative procedures. Processing specimens in batches could help save time in highly automated assays (e.g., line-probe) (TTPS 00:14:00 vs. 00:09:45 for batches comprising 7 and 31 specimens, respectively).CONCLUSIONS: The T&M tool can be considered a universal and objective methodology contributing to workload assessment in TB diagnostic laboratories. Comparison of workload between laboratories could help laboratory managers justify their resource and personnel needs for the implementation of novel, time-saving, cost-effective technologies, as well as identify areas for improvement.
Abubakar I, Drobniewski F, Southern J, et al., 2017, PROGNOSTIC VALUE OF INTERFERON GAMMA RELEASE ASSAYS AND TUBERCULIN SKIN TEST IN PREDICTING THE DEVELOPMENT OF ACTIVE TUBERCULOSIS: THE UK PREDICT TB COHORT STUDY, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A22-A22, ISSN: 0040-6376
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Balabanova Y, Fiebig L, Ignatyeva O, et al., 2017, Multidrug-resistant TB in Eastern region of the EU: is the shorter regimen an exception or a rule?, Thorax, Vol: 72, Pages: 850-852, ISSN: 1468-3296
WHO recently recommended the use of a shorter multidrug-resistant TB (MDR-TB) regimen under programmatic conditions. We assessed eligibility for this regimen in a cohort of 737 adult patients with MDR-TB from Latvia, Lithuania, Estonia and Bucharest city recruited in 2007 and 2009. Only 4.2% of the patients were eligible for this regimen. Ethambutol (64%), pyrazinamide resistance (58%) and previous exposure to second-line TB drugs were major reasons for non-eligibility. High-level resistance to isoniazid is expected due to widespread prevalence of katG mutations. In Eastern Europe, the use of the shorter regimen might be an exception rather than a rule.
Drobniewski F, Ehsani S, Dara M, 2017, Fighting drug-resistant tuberculosis in eastern Europe, Lancet Infectious Diseases, Vol: 17, Pages: 691-692, ISSN: 1473-3099
Bielecka MK, Tezera LB, Zmijan R, et al., 2017, A bioengineered three-dimensional cell culture platform integrated with microfluidics to address antimicrobial resistance in tuberculosis, MBIO, Vol: 8, ISSN: 2150-7511
Antimicrobial resistance presents one of the most significant threats to human health, with the emergence of totally drug-resistant organisms. We have combined bioengineering, genetically modified bacteria, longitudinal readouts, and fluidics to develop a transformative platform to address the drug development bottleneck, utilizing Mycobacterium tuberculosis as the model organism. We generated microspheres incorporating virulent reporter bacilli, primary human cells, and an extracellular matrix by using bioelectrospray methodology. Granulomas form within the three-dimensional matrix, and mycobacterial stress genes are upregulated. Pyrazinamide, a vital first-line antibiotic for treating human tuberculosis, kills M. tuberculosis in a three-dimensional culture but not in a standard two-dimensional culture or Middlebrook 7H9 broth, demonstrating that antibiotic sensitivity within microspheres reflects conditions in patients. We then performed pharmacokinetic modeling by combining the microsphere system with a microfluidic plate and demonstrated that we can model the effect of dynamic antibiotic concentrations on mycobacterial killing. The microsphere system is highly tractable, permitting variation of cell content, the extracellular matrix, sphere size, the infectious dose, and the surrounding medium with the potential to address a wide array of human infections and the threat of antimicrobial resistance.
Kontsevaya I, Nikolayevskyy V, Kovalyov A, et al., 2016, Tuberculosis cases caused by heterogeneous infection in Eastern Europe and their influence on outcomes, Infection Genetics and Evolution, Vol: 48, Pages: 76-82, ISSN: 1567-1348
INTRODUCTION: Mycobacterium tuberculosis superinfection is known to occur in areas with high rates of tuberculosis (TB) and has a significant impact on overall clinical TB management. AIM: We aimed to estimate the superinfection rate in cohorts of drug sensitive and multi-drug resistant tuberculosis (MDR TB) patients from Eastern Europe and the potential role of a second MDR TB strain infecting a patient with active non-MDR TB in treatment outcome. METHODS: The study population included 512 serial M. tuberculosis isolates obtained from 84 MDR- and 136 non-MDR TB patients recruited sequentially at sites in Lithuania, Latvia and Russia in 2011-2013. Strains were genotyped using standardized 24-loci Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) typing. RESULTS: Changes in two or more MIRU-VNTR loci suggesting superinfection were detected in 13 patients (5.9%). We found 4 initially non-MDR TB patients superinfected with an MDR TB strain during treatment and 3 of them had an unsuccessful outcome. CONCLUSIONS: An unsuccessful treatment outcome in patients initially diagnosed with drug sensitive TB might be explained by superinfection with an MDR TB strain. Bacteriological reversion could be indicative of superinfection with another strain. Archiving of all serial isolates and their genotyping in case of culture reversion could support therapeutic strategies in high MDR TB burden settings if resources are available.
Gonzalo X, Claxton P, Brown T, et al., 2016, True rifampicin resistance missed by the MGIT: prevalence of this pheno/genotype in the UK and Ireland after 18 month surveillance, Clinical Microbiology and Infection, Vol: 23, Pages: 260-263, ISSN: 1469-0691
OBJECTIVES: To characterize rifampicin-resistant strains missed by the Mycobacteria Growth Indicator Tube (MGIT) 960 system but not by egg-based media in the UK and Ireland and to ascertain their prevalence. METHODS: All strains sent for second-line susceptibility testing were prospectively collected. Drug Susceptibility Testing was performed by Resistance Ratio (RR), Proportion Method (PM), MGIT 960 and MIC determination by microdilution. Rifampicin-resistance-conferring mutations were detected with line probe assays and sequencing. At the end of the study period, retrospective archived strains from 2010 to 2014 showing key mutations were analysed phenotypically and genotypically. RESULTS: Seventeen of 7234 prospective isolates were included. All of them were susceptible by MGIT. One was borderline by RR (MIC to rifampicin of 4 mg/L) and was resistant by PM. Eight were resistant and eight were highly resistant on RR. These 16 isolates had MICs between 1 and 8 mg/L on microdilution. With PM, 16/17 were susceptible to rifampicin. 17/17 had mutations in the rpoB gene. D516Y was the mutation most frequently found (13/17). Retrospectively, ten additional strains with key genotypes were found in our collection: 6/10 were susceptible in the MGIT and resistant in RR. Of the 27 studied strains, the MGIT only detected resistance in four. CONCLUSIONS: Rifampicin resistance is missed by the MGIT system. In the UK and Ireland the prevalence of these strains is low. The introduction of routine molecular testing would detect false susceptibility. Further research is needed to ascertain the role of these strains in clinical failure and their prevalence in other settings.
Zheng X, Ning Z, Drobniewski F, et al., 2016, pncA mutations are associated with slower sputum conversion during standard treatment of multidrug-resistant tuberculosis, INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, Vol: 49, Pages: 183-188, ISSN: 0924-8579
Casali N, Broda A, Harris SR, et al., 2016, Whole Genome Sequence Analysis of a Large Isoniazid-Resistant Tuberculosis Outbreak in London: A Retrospective Observational Study, PLOS Medicine, Vol: 13, ISSN: 1549-1277
BACKGROUND: A large isoniazid-resistant tuberculosis outbreak centred on London, United Kingdom, has been ongoing since 1995. The aim of this study was to investigate the power and value of whole genome sequencing (WGS) to resolve the transmission network compared to current molecular strain typing approaches, including analysis of intra-host diversity within a specimen, across body sites, and over time, with identification of genetic factors underlying the epidemiological success of this cluster. METHODS AND FINDINGS: We sequenced 344 outbreak isolates from individual patients collected over 14 y (2 February 1998-22 June 2012). This demonstrated that 96 (27.9%) were indistinguishable, and only one differed from this major clone by more than five single nucleotide polymorphisms (SNPs). The maximum number of SNPs between any pair of isolates was nine SNPs, and the modal distance between isolates was two SNPs. WGS was able to reveal the direction of transmission of tuberculosis in 16 cases within the outbreak (4.7%), including within a multidrug-resistant cluster that carried a rare rpoB mutation associated with rifampicin resistance. Eleven longitudinal pairs of patient pulmonary isolates collected up to 48 mo apart differed from each other by between zero and four SNPs. Extrapulmonary dissemination resulted in acquisition of a SNP in two of five cases. WGS analysis of 27 individual colonies cultured from a single patient specimen revealed ten loci differed amongst them, with a maximum distance between any pair of six SNPs. A limitation of this study, as in previous studies, is that indels and SNPs in repetitive regions were not assessed due to the difficulty in reliably determining this variation. CONCLUSIONS: Our study suggests that (1) certain paradigms need to be revised, such as the 12 SNP distance as the gold standard upper threshold to identify plausible transmissions; (2) WGS technology is helpful to rule out the possibility of direct transmission when isolat
Papaventsis D, Casali N, Kontsevaya I, et al., 2016, Whole genome sequencing of M. tuberculosis for detection of drug resistance: a systematic review, Clinical Microbiology and Infection, Vol: 23, Pages: 61-68, ISSN: 1469-0691
OBJECTIVES: We conducted a systematic review to determine the diagnostic accuracy of Whole Genome Sequencing (WGS) of M. tuberculosis for the detection of resistance to first and second line anti-tuberculosis (TB) drugs. METHODS: The study was conducted according to the criteria of the Preferred Reporting Items for Systematic Reviews group. A total of 20 publications were included. The sensitivity, specificity, PPV and NPV of WGS using phenotypic Drug Susceptibility Testing (DST) methods as a gold standard were determined. RESULTS: Anti-TB agents tested included all first line drugs, a variety of reserve drugs, as well as new drugs. Polymorphisms in a total of 53 genes were tested for associations with drug resistance. Pooled sensitivity and specificity values for detection of resistance to selected first line drugs were 0.98 (95% CI, 0.93 to 0.98) and 0.98 (95% CI, 0.98 to 1.00) for rifampicin and 0.97 (95% CI, 0.94 to 0.99) and 0.93 (95% CI 0.91 to 0.96) for isoniazid, respectively. Due to high heterogeneity in studies' design, lack of data, knowledge of resistance mechanisms and clarity on exclusion of phylogenetic markers, there was a significant variation in analytical performance of WGS for the remaining first-line, reserved drugs and new drugs. CONCLUSIONS: WGS could be considered a promising alternative to existing phenotypic and molecular DST methods for rifampicin and isoniazid pending standardization of analytical pipelines. To ensure clinical relevance of WGS for detection of M. tuberculosis complex drug resistance, future studies should include information on clinical outcomes.
Li D, Hu Y, Werngren J, et al., 2016, Emergence and genetic characteristics of pyrazinamide resistant tuberculosis in China, a multi-center study, Antimicrobial Agents and Chemotherapy, Vol: 60, Pages: 5159-5166, ISSN: 1098-6596
Background: The aim of this study was to investigate the rates of pyrazinamide (PZA) resistance and the associated risk factors as well as to evaluate the pncA gene loci as a marker for PZA resistance in China.Method: A population-based multi-center study of pulmonary TB cases was carried out from 2011 to 2013 in four Chinese district/counties with different geographic and socio-economic features. Testing for multidrug-resistant tuberculosis (MDR-TB) and susceptibility to PZA were determined by the proportion method on Löwenstein-Jensen medium and BACTEC MGIT 960 respectively. Mutations in the pncA gene were identified by sequencing.Results: Among 878 culture positive cases, 147(16.7%) were resistant to PZA, with a significantly higher proportion among MDR isolates compared to the drug sensitive isolates (30.2% VS 7.7%, p<0.001). Totally, 136 isolates had a non-synonymous pncA mutation, with a comparable diagnostic performance between Beijing family and non-Beijing family as well as between MDR-TB and 1st-line drug susceptible TB. Furthermore, the mutations in isolates with high-level PZA resistance (MIC>500mg/L) were observed mainly in three regions of the pncA gene (codon 51-76, codon 130-142 and codon 163-180). Patients with prior treatment history had a significantly higher risk for PZA mono-resistance (OR:2.86,95%CI:1.363-6.015) and MDR PZA resistance (OR:6.47, 95%CI:3.186-13.15), while the additional factors associated with MDR-PZA resistance were the patient's age (OR:1.02, 95%CI:1.003-1.042), lung cavity (OR:2.64, 95%CI:1.296-5.391).Conclusions: These findings suggest that it is a priority to identify PZA resistance in MDR-TB and a rapid molecular diagnostic test based on pncA mutations in the Chinese settings where MDR-TB prevalence is high should be developed.
Nikolayevskyy V, Hillemann D, Richter E, et al., 2016, External quality assessment for tuberculosis diagnosis and drug resistance in the European Union: a five year multicentre implementation study, PLOS One, Vol: 11, ISSN: 1932-6203
Balabanova Y, Ignatyeva O, Fiebig L, et al., 2016, Survival of patients with multidrug-resistant TB in Eastern Europe: what makes a difference?, Thorax, Vol: 71, Pages: 854-861, ISSN: 1468-3296
Background The quality of care for patients with TB in Eastern Europe has improved significantly; nevertheless drug resistance rates remain high. We analysed survival in a cohort of patients with multidrug-resistant and extensively drug-resistant (MDR-/XDR-) TB from Latvia, Lithuania, Estonia and Bucharest city.Methods Consecutive adult new and retreatment patients with culture-confirmed pulmonary MDR-TB registered for treatment in 2009 (and in 2007 in Latvia) were enrolled; prospective survival information was collected.Results A total of 737 patients were included into the cohort. Of all MDR-TB cases, 46% were newly diagnosed; 56% of all MDR-TB cases had no additional resistance to fluoroquinolones or injectable agents, 33% had pre-XDR-TB and 11% XDR-TB. Median survival was 5.9 years in patients with MDR-TB and XDR-TB; 1.9 years in patients coinfected with HIV. Older age, male gender, alcohol abuse, retirement, co-morbidities, extrapulmonary involvement and HIV coinfection independently worsened survival. Inclusion of fluoroquinolones and injectable agents improves survival in patients with MDR-TB. Pre-XDR and XDR status did not significantly shorten survival as long as fluoroquinolones and injectable agents were part of the regimen. Moxifloxacin seems to improve survival in ofloxacin-susceptible patients when compared with older generation fluoroquinolones.Conclusions The burden of additional resistances in patients with MDR-TB is high likely due to primary transmission of resistant strains. Social and programmatic factors including management of alcohol dependency, expansion of HIV testing and antiretroviral treatment need to be addressed in order to achieve cure and to interrupt transmission. The role of last generation fluoroquinolones and injectable agents in treatment of patients with pre-XDR and XDR-TB needs to be further investigated.
Nikolayevskyy V, Kranzer K, Niemann S, et al., 2016, Whole genome sequencing of Mycobacteriumtuberculosis for detection of recent transmission and tracing outbreaks: a systematic review, Tuberculosis, Vol: 98, Pages: 77-85, ISSN: 1873-281X
Nikolayevskyy V, Trovato A, Broda A, et al., 2016, MIRU-VNTR genotyping of Mycobacterium tuberculosis strains using QIAxcel technology: a multicentre evaluation study, PLOS One, Vol: 11, ISSN: 1932-6203
Pink F, Brown TJ, Kranzer K, et al., 2016, Evaluation of Xpert MTB/RIF for detection of Mycobacterium tuberculosis in cerebrospinal fluid, Journal of Clinical Microbiology, Vol: 54, Pages: 809-811, ISSN: 1098-660X
Cabibbe AM, Miotto P, Moure R, et al., 2015, Lab-on-Chip-Based Platform for Fast Molecular Diagnosis of Multidrug-Resistant Tuberculosis, Journal of Clinical Microbiology, Vol: 53, Pages: 3876-3880, ISSN: 0095-1137
We evaluated the performance of the molecular lab-on-chip-based VerePLEX Biosystem for detection of multidrug-resistanttuberculosis (MDR-TB), obtaining a diagnostic accuracy of more than 97.8% compared to sequencing and MTBDRplus assay forMycobacterium tuberculosis complex and rifampin and isoniazid resistance detection on clinical isolates and smear-positivespecimens. The speed, user-friendly interface, and versatility make it suitable for routine laboratory use.
Balabanova Y, Nikolayevskyy V, Ignatyeva O, et al., 2015, Beijing clades of <i>Mycobacterium tuberculosis</i> are associated with differential survival in HIV-negative Russian patients, INFECTION GENETICS AND EVOLUTION, Vol: 36, Pages: 517-523, ISSN: 1567-1348
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Kranzer K, Elamin WF, Cox H, et al., 2015, A systematic review and meta-analysis of the efficacy and safety of <i>N</i>-acetylcysteine in preventing aminoglycoside-induced ototoxicity: implications for the treatment of multidrug-resistant TB, THORAX, Vol: 70, Pages: 1070-1077, ISSN: 0040-6376
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- Citations: 42
Walker TM, Kohl TA, Omar SV, et al., 2015, Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study, Lancet Infectious Diseases, Vol: 15, Pages: 1193-1202, ISSN: 1473-3099
BackgroundDiagnosing drug-resistance remains an obstacle to the elimination of tuberculosis. Phenotypic drug-susceptibility testing is slow and expensive, and commercial genotypic assays screen only common resistance-determining mutations. We used whole-genome sequencing to characterise common and rare mutations predicting drug resistance, or consistency with susceptibility, for all first-line and second-line drugs for tuberculosis.MethodsBetween Sept 1, 2010, and Dec 1, 2013, we sequenced a training set of 2099 Mycobacterium tuberculosis genomes. For 23 candidate genes identified from the drug-resistance scientific literature, we algorithmically characterised genetic mutations as not conferring resistance (benign), resistance determinants, or uncharacterised. We then assessed the ability of these characterisations to predict phenotypic drug-susceptibility testing for an independent validation set of 1552 genomes. We sought mutations under similar selection pressure to those characterised as resistance determinants outside candidate genes to account for residual phenotypic resistance.FindingsWe characterised 120 training-set mutations as resistance determining, and 772 as benign. With these mutations, we could predict 89·2% of the validation-set phenotypes with a mean 92·3% sensitivity (95% CI 90·7–93·7) and 98·4% specificity (98·1–98·7). 10·8% of validation-set phenotypes could not be predicted because uncharacterised mutations were present. With an in-silico comparison, characterised resistance determinants had higher sensitivity than the mutations from three line-probe assays (85·1% vs 81·6%). No additional resistance determinants were identified among mutations under selection pressure in non-candidate genes.InterpretationA broad catalogue of genetic mutations enable data from whole-genome sequencing to be used clinically to predict drug resistance, drug susceptibility, or to ident
Ignatyeva O, Balabanova Y, Nikolayevskyy V, et al., 2015, Resistance profile and risk factors of drug resistant tuberculosis in the Baltic countries, TUBERCULOSIS, Vol: 95, Pages: 581-588, ISSN: 1472-9792
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Brown AC, Bryant JM, Einer-Jensen K, et al., 2015, Rapid Whole-Genome Sequencing of <i>Mycobacterium</i> <i>tuberculosis</i> Isolates Directly from Clinical Samples, JOURNAL OF CLINICAL MICROBIOLOGY, Vol: 53, Pages: 2230-2237, ISSN: 0095-1137
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- Citations: 172
Seoudi N, Bergmeier LA, Drobniewski F, et al., 2015, The oral mucosal and salivary microbial community of Behcet's syndrome and recurrent aphthous stomatitis, Journal of Oral Microbiology, Vol: 7, ISSN: 2000-2297
Background: Behçet’s syndrome (BS) is a multisystem immune-related disease of unknown etiology. Recurrent aphthous stomatitis (RAS) is characterized by the presence of idiopathic oral ulceration without extraoral manifestation. The interplay between the oral microbial communities and the immune response could play an important role in the etiology and pathogenesis of both BS and RAS.Objective: To investigate the salivary and oral mucosal microbial communities in BS and RAS.Methods: Purified microbial DNA isolated from saliva samples (54 BS, 25 healthy controls [HC], and 8 RAS) were examined by the human oral microbe identification microarray. Cultivable salivary and oral mucosal microbial communities from ulcer and non-ulcer sites were identified by matrix-assisted laser desorption/ionization time-of-flight analysis. Mycobacterium spp. were detected in saliva and in ulcer and non-ulcer oral mucosal brush biopsies following culture on Lowenstein-Jensen slopes and Mycobacterial Growth Indicator Tubes.Results: There was increased colonization with Rothia denticariosa of the non-ulcer sites of BS and RAS patients (p<0.05). Ulcer sites in BS were highly colonized with Streptococcus salivarius compared to those of RAS (p<0.05), and with Streptococcus sanguinis compared to HC (p<0.0001). Oral mucosa of HC were more highly colonized with Neisseria and Veillonella compared to all studied groups (p<0.0001).Conclusions: Despite the uncertainty whether the reported differences in the oral mucosal microbial community of BS and RAS are of causative or reactive nature, it is envisaged that restoring the balance of the oral microbial community of the ulcer sites may be used in the future as a new treatment modality for oral ulceration.
Pardieu C, Casali N, Clark SO, et al., 2015, Correlates between Models of Virulence for <i>Mycobacterium tuberculosis</i> among Isolates of the Central Asian Lineage: a Case for Lysozyme Resistance Testing?, INFECTION AND IMMUNITY, Vol: 83, Pages: 2213-2223, ISSN: 0019-9567
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