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Borstel-Hohenraden, Germany

Niemann S.,National Reference Center for Mycobacteria | Diel R.,Hannover Medical School | Khechinashvili G.,Georgian Foundation Against Tuberculosis and Lung Diseases | Gegia M.,Georgian Foundation Against Tuberculosis and Lung Diseases | And 2 more authors.
Journal of Clinical Microbiology | Year: 2010

High rates and transmission of multidrug-resistant (MDR) tuberculosis (TB) have been associated with the Mycobacterium tuberculosis complex (MTBC) Beijing lineage, pointing to the importance of pathogen genetic factors for the modulation of infection outcome and epidemiology. We present here an in-depth analysis of the population structure of MTBC strains from the Republic of Georgia, a high-incidence setting at the Black Sea Coast. Phylogenetic lineages were identified based on 24-locus MIRU-VNTR (for mycobacterial interspersed repetitive unit-variable number tandem repeat) and spoligotyping analysis. Clusters of strains with identical genotyping profiles were determined as an indicator for the rate of recent transmission. Among the 183 M. tuberculosis isolates investigated, the most prominent lineage found was Beijing (26%), followed by the LAM (18%), Ural (12%), and Haarlem (5%) strains. A closely related previously undefined phylogenetic group (62 strains) showed a genotyping pattern similar to laboratory strain H37RV and was denominated as "Georgia-H37RV-like." Although isoniazid resistance was found among strains of different lineages, MDR TB was nearly completely restricted to Beijing strains (P < 0.0001). Approximately 50% of the isolates were grouped in clusters, indicating a high rate of recent transmission. Our data indicate that, in addition to the confirmation of the importance of Beijing genotype strains for the TB epidemiology in former Soviet Union countries, a high-population diversity with strains of the LAM, Ural, Haarlem, and a previously undefined lineage represents nearly two-thirds of the strains found in Georgia. Higher rates among previously treated and MDR TB patients point to a higher potential of lineage Beijing to escape therapy and develop MDR TB. Copyright © 2010, American Society for Microbiology. All Rights Reserved. Source


Folkvardsen D.B.,Statens Serum Institute | Svensson E.,Statens Serum Institute | Thomsen V.O.,Statens Serum Institute | Rasmussen E.M.,Statens Serum Institute | And 5 more authors.
Journal of Clinical Microbiology | Year: 2013

Patients may harbor both drug-susceptible and -resistant bacteria, representing heteroresistance. We studied mixtures of isoniazid- resistant and -susceptible Mycobacterium tuberculosis strains. Conventional drug susceptibility testing was the most sensitive method of detection, whereas the line probe assay and sequencing were not able to detect the clinically relevant 1% proportion of resistant bacteria. Copyright © 2013, American Society for Microbiology. Source


Genc G.E.,Istanbul University | Richter E.,National Reference Center for Mycobacteria | Erturan Z.,Istanbul University
APMIS | Year: 2013

Nontuberculous mycobacteria (NTM) are ubiquitous in hot and cold water distribution systems. With molecular typing methods it was shown that water can be the source of colonization and infection with NTM. The aim of our study was the investigation of NTM in hot and cold water samples taken from various departments of two hospitals in Istanbul, Turkey. Totally, 160 water samples were examined. The temperature, pH, and free chlorine levels of water samples were measured between 10-41 °C, 6.78-7.98 and <0.3-0.5 mg/L, respectively. NTM were detected in 33 (20.6%) samples. Totally 20 (60.6%), 10 (30.3%) and 3 (9.1%) isolates were identified as Mycobacterium lentiflavum, Mycobacterium gordonae, and Mycobacterium peregrinum, respectively. M. lentiflavum, which was the most frequently isolated NTM, is characterized by multiple resistance to antimycobacterial drugs. Although no infections with this mycobacterium were reported from our country so far, preventive measures may be considered in patients under immunosuppression. Because no significant correlations were found among the presence of NTM or species distribution and water temperature, pH or free chlorine levels, other factors need to be investigated. © 2013 APMIS. Source


Diel R.,Hannover Medical School | Loddenkemper R.,German Central Committee Against Tuberculosis | Niemann S.,National Reference Center for Mycobacteria | Nienhaus A.,Institution for Statutory Accident Insurance and Prevention in the Health and Welfare Services
American Journal of Respiratory and Critical Care Medicine | Year: 2011

Rationale: Only limited data are available on the predictive value of interferon-γ release assays for progression from latent tuberculosis infection to active tuberculosis (TB). Objectives: To build on our initial study comparing the QuantiFERON-TB Gold in-tube assay (QFT) with the tuberculin skin test (TST) in close contacts of patients with TB and evaluating progression to active TB for up to 4 years. Methods: A cohort of close contacts of smear-positive index cases established between May 2005 and April 2008 was tested with QFT and TST. Through April 2010, progressors to active TB were consecutively recorded. Measurements and Main Results: Of the 1,414 contacts (141 children), 1,033 were still resident in Hamburg at the end of the study period, and results of both tests were available for 954. QFT, but not TST, results were associated with exposure time (P < 0.0001). For QFT, 198 of 954 (20.8%) were positive; 63.3% (604) were TST positive at greater than 5 mm and 25.4% at greater than 10 mm. Nine hundred and three contacts refused chemoprevention and 19 developed active TB. All 19 (100%) had been QFT positive with a progression rate of 12.9% (19 of 147) over the observation period. Corresponding values for the TST were significantly lower: 89.5% (17 of 19) and 3.1% (17 of 555) at greater than 5 mm, and 52.6% (10 of 19) and 4.8% (10 of 207) at greater than 10 mm, respectively. The progression rate of 28.6% (6 of 21) for QFT-positive children was significantly higher than 10.3% (13 of 126) for adults (P = 0.03). Conclusions: Results suggest that QFT is more reliable than the TST for identifying those who will soon progress to active TB, especially in children. Source


Roetzer A.,Molecular Mycobacteriology | Diel R.,University of Kiel | Kohl T.A.,Molecular Mycobacteriology | Kohl T.A.,Bielefeld University | And 10 more authors.
PLoS Medicine | Year: 2013

Background: Understanding Mycobacterium tuberculosis (Mtb) transmission is essential to guide efficient tuberculosis control strategies. Traditional strain typing lacks sufficient discriminatory power to resolve large outbreaks. Here, we tested the potential of using next generation genome sequencing for identification of outbreak-related transmission chains. Methods and Findings: During long-term (1997 to 2010) prospective population-based molecular epidemiological surveillance comprising a total of 2,301 patients, we identified a large outbreak caused by an Mtb strain of the Haarlem lineage. The main performance outcome measure of whole genome sequencing (WGS) analyses was the degree of correlation of the WGS analyses with contact tracing data and the spatio-temporal distribution of the outbreak cases. WGS analyses of the 86 isolates revealed 85 single nucleotide polymorphisms (SNPs), subdividing the outbreak into seven genome clusters (two to 24 isolates each), plus 36 unique SNP profiles. WGS results showed that the first outbreak isolates detected in 1997 were falsely clustered by classical genotyping. In 1998, one clone (termed "Hamburg clone") started expanding, apparently independently from differences in the social environment of early cases. Genome-based clustering patterns were in better accordance with contact tracing data and the geographical distribution of the cases than clustering patterns based on classical genotyping. A maximum of three SNPs were identified in eight confirmed human-to-human transmission chains, involving 31 patients. We estimated the Mtb genome evolutionary rate at 0.4 mutations per genome per year. This rate suggests that Mtb grows in its natural host with a doubling time of approximately 22 h (400 generations per year). Based on the genome variation discovered, emergence of the Hamburg clone was dated back to a period between 1993 and 1997, hence shortly before the discovery of the outbreak through epidemiological surveillance. Conclusions: Our findings suggest that WGS is superior to conventional genotyping for Mtb pathogen tracing and investigating micro-epidemics. WGS provides a measure of Mtb genome evolution over time in its natural host context. Please see later in the article for the Editors' Summary. © 2013 Roetzer et al. Source

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