scholarly journals Tuberculosis Outbreak in an Educational Institution in Norway

2017 ◽  
Vol 55 (5) ◽  
pp. 1327-1333 ◽  
Author(s):  
Gunnstein Norheim ◽  
Siri Seterelv ◽  
Trude M. Arnesen ◽  
Anne Torunn Mengshoel ◽  
Tone Tønjum ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pulmonary Tuberculosis ◽  
Index Case ◽  
Educational Institution ◽  
Variable Number Tandem Repeat ◽  
Variable Number ◽  
Contact Tracing ◽  
Whole Genome ◽  
Content Type ◽  
Transmission Chain

ABSTRACTWithin 1 week in April 2013, three cases of pulmonary tuberculosis (TB) were reported among students attending training sessions at an educational institution in Oslo, Norway. By the end of October 2013, a total of nine epidemiologically linked cases had been reported. The outbreak encompassed a total of 24 cases from 2009 to 2014, among which all of the 22Mycobacterium tuberculosisisolates available had identical mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) profiles (MtbC15-9 code 10287-189) belonging to the Beijing lineage. Whole-genome sequencing (WGS) of theM. tuberculosisisolates revealed 20 variable nucleotide positions within the cluster, indicating a clonal outbreak. The most likely index case was identified and diagnosed in Norway in 2009 but was born in Asia. WGS analyses verified that all of the cases were indeed part of a single transmission chain. However, even when combining WGS and intensified contact tracing, we were unable to fully reconstruct the TB transmission events.

scholarly journals A Predominant Variable-Number Tandem-Repeat Cluster of Mycobacterium tuberculosis Isolates among Asylum Seekers in the Netherlands and Denmark, Deciphered by Whole-Genome Sequencing

2017 ◽  
Vol 56 (2) ◽  
Author(s):  
Rana Jajou ◽  
Albert de Neeling ◽  
Erik Michael Rasmussen ◽  
Anders Norman ◽  
Arnout Mulder ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
The Netherlands ◽  
Genetic Distance ◽  
Genome Sequencing ◽  
Tandem Repeat ◽  
Variable Number Tandem Repeat ◽  
Variable Number ◽  
Whole Genome ◽  
Average Genetic Distance ◽  
Content Type

ABSTRACT In many countries, Mycobacterium tuberculosis isolates are routinely subjected to variable-number tandem-repeat (VNTR) typing to investigate M. tuberculosis transmission. Unexpectedly, cross-border clusters were identified among African refugees in the Netherlands and Denmark, although transmission in those countries was unlikely. Whole-genome sequencing (WGS) was applied to analyze transmission in depth and to assess the precision of VNTR typing. WGS was applied to 40 M. tuberculosis isolates from refugees in the Netherlands and Denmark (most of whom were from the Horn of Africa) that shared the exact same VNTR profile. Cluster investigations were undertaken to identify in-country epidemiological links. Combining WGS results for the isolates (all members of the central Asian strain [CAS]/Delhi genotype), from both European countries, an average genetic distance of 80 single-nucleotide polymorphisms (SNPs) (maximum, 153 SNPs) was observed. The few pairs of isolates with confirmed epidemiological links, except for one pair, had a maximum distance of 12 SNPs. WGS divided this refugee cluster into several subclusters of patients from the same country of origin. Although the M. tuberculosis cases, mainly originating from African countries, shared the exact same VNTR profile, most were clearly distinguished by WGS. The average genetic distance in this specific VNTR cluster was 2 times greater than that in other VNTR clusters. Thus, identical VNTR profiles did not represent recent direct M. tuberculosis transmission for this group of patients. It appears that either these strains from Africa are extremely conserved genetically or there is ongoing transmission of this genotype among refugees on their long migration routes from Africa to Europe.

scholarly journals Mycobacterium tuberculosis Lineage 7 Strains Are Associated with Prolonged Patient Delay in Seeking Treatment for Pulmonary Tuberculosis in Amhara Region, Ethiopia

2015 ◽  
Vol 53 (4) ◽  
pp. 1301-1309 ◽  
Author(s):  
Solomon A. Yimer ◽  
Gunnstein Norheim ◽  
Amine Namouchi ◽  
Ephrem D. Zegeye ◽  
Wibeke Kinander ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Variable Number Tandem Repeat ◽  
Bioinformatic Analysis ◽  
Variable Number ◽  
Patient Delay ◽  
Contact Tracing ◽  
Amhara Region ◽  
Study Region ◽  
Content Type ◽  
Delay In Seeking Treatment

Recent genotyping studies ofMycobacterium tuberculosisin Ethiopia have reported the identification of a new phylogenetically distinctM. tuberculosislineage, lineage 7. We therefore investigated the genetic diversity and association of specificM. tuberculosislineages with sociodemographic and clinical parameters among pulmonary TB patients in the Amhara Region, Ethiopia. DNA was isolated fromM. tuberculosis-positive sputum specimens (n= 240) and analyzed by PCR and 24-locus mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) analysis and spoligotyping. Bioinformatic analysis assigned theM. tuberculosisgenotypes to global lineages, and associations between patient characteristics and genotype were evaluated using logistic regression analysis. The study revealed a high diversity of modern and premodernM. tuberculosislineages, among which approximately 25% were not previously reported. Among theM. tuberculosisstrains (n= 138) assigned to seven subgroups, the largest cluster belonged to the lineage Central Asian (CAS) (n= 60; 26.0%), the second largest to lineage 7 (n= 36; 15.6%), and the third largest to the lineage Haarlem (n= 35; 15.2%). Four sublineages were new in the MIRU-VNTRplus database, designated NW-ETH3, NW-ETH1, NW-ETH2, and NW-ETH4, which included 24 (10.4%), 18 (7.8%), 8 (3.5%), and 5 (2.2%) isolates, respectively. Notably, patient delay in seeking treatment was significantly longer among patients infected with lineage 7 strains (Mann-Whitney test,P< 0.008) than in patients infected with CAS strains (adjusted odds ratio [AOR], 4.7; 95% confidence interval [CI], 1.6 to 13.5). Lineage 7 strains also grew more slowly than otherM. tuberculosisstrains. Cases of Haarlem (OR, 2.8; 95% CI, 1.2 to 6.6) and NW-ETH3 (OR, 2.8; 95% CI, 1.0 to 7.3) infection appeared in defined clusters. Intensified active case finding and contact tracing activities in the study region are needed to expedite diagnosis and treatment of TB.

scholarly journals Prediction of Local Transmission of Mycobacterium tuberculosis Isolates of a Predominantly Beijing Lineage by Use of a Variable-Number Tandem-Repeat Typing Method Incorporating a Consensus Set of Hypervariable Loci

2017 ◽  
Vol 56 (1) ◽  
Author(s):  
Yoshiro Murase ◽  
Kiyohiko Izumi ◽  
Akihiro Ohkado ◽  
Akio Aono ◽  
Kinuyo Chikamatsu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Tandem Repeat ◽  
Variable Number Tandem Repeat ◽  
Variable Number ◽  
Trend Test ◽  
Typing Method ◽  
Content Type ◽  
Tuberculosis Transmission ◽  
High Prevalence ◽  
Hypervariable Loci

ABSTRACT Strain genotyping based on the variable-number tandem repeat (VNTR) is widely applied for identifying the transmission of Mycobacterium tuberculosis. A consensus set of four hypervariable loci (1982, 3232, 3820, and 4120) has been proposed to improve the discrimination of Beijing lineage strains. Herein, we evaluated the utility of these four hypervariable loci for tracing local tuberculosis transmission in 981 cases over a 14-month period in Japan (2010 to 2011). We used six different VNTR systems, with or without the four hypervariable loci. Patient ages and weighted standard distances (a measure of the dispersion of genotype-clustered cases) were used as proxies for estimating local tuberculosis transmission. The highest levels of isolate discrimination were achieved with VNTR systems that incorporated the four hypervariable loci (i.e., the Japan Anti-Tuberculosis Association [JATA]18-VNTR, mycobacterial interspersed repetitive unit [MIRU]28-VNTR, and 24Beijing-VNTR). The clustering rates by JATA12-VNTR, MIRU15-VNTR, JATA15-VNTR, JATA18-VNTR, MIRU28-VNTR, and 24Beijing-VNTR systems were 52.2%, 51.0%, 39.0%, 24.1%, 23.1%, and 22.0%, respectively. As the discriminative power increased, the median weighted standard distances of the clusters tended to decrease (from 311 to 80 km, P < 0.001, Jonckheere-Terpstra trend test). Concurrently, the median ages of patients in the clusters tended to decrease (from 68 to 60 years, P < 0.001, Jonckheere-Terpstra trend test). These findings suggest that strain typing using the four hypervariable loci improves the prediction of active local tuberculosis transmission. The four-locus set can therefore contribute to the targeted control of tuberculosis in settings with high prevalence of Beijing lineage strains.

scholarly journals Whole-Genome Sequencing of Streptomycin-Resistant Mycobacterium tuberculosis Strain SBH145 from Sabah, Malaysia

2022 ◽  
Author(s):  
Zainal Arifin Mustapha ◽  
Jaeyres Jani ◽  
Cheronie Shely Stanis ◽  
Dg Syahidah Nadiah Abdull Majid ◽  
Chin Kai Ling ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pulmonary Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
The Philippines ◽  
Whole Genome ◽  
Content Type ◽  
Tuberculosis Strain ◽  
Mycobacterium Tuberculosis Strain ◽  
Malaysian Borneo

This paper reports on the whole-genome sequencing of a streptomycin-resistant Mycobacterium tuberculosis strain that was isolated from a patient with pulmonary tuberculosis in Sabah state of Malaysian Borneo. The strain belongs to the EAI2-Manila family of lineage 1 and is clustered with M. tuberculosis strains from the Philippines, India, and Taiwan.

scholarly journals Prospective Whole-Genome Sequencing Enhances National Surveillance of Listeria monocytogenes

2015 ◽  
Vol 54 (2) ◽  
pp. 333-342 ◽  
Author(s):  
Jason C. Kwong ◽  
Karolina Mercoulia ◽  
Takehiro Tomita ◽  
Marion Easton ◽  
Hua Y. Li ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Variable Number Tandem Repeat ◽  
Variable Number ◽  
Outbreak Detection ◽  
Whole Genome ◽  
Genetic Population ◽  
Content Type ◽  
Epidemiologic Surveillance

Whole-genome sequencing (WGS) has emerged as a powerful tool for comparing bacterial isolates in outbreak detection and investigation. Here we demonstrate that WGS performed prospectively for national epidemiologic surveillance ofListeria monocytogeneshas the capacity to be superior to our current approaches using pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), multilocus variable-number tandem-repeat analysis (MLVA), binary typing, and serotyping. Initially 423L. monocytogenesisolates underwent WGS, and comparisons uncovered a diverse genetic population structure derived from three distinct lineages. MLST, binary typing, and serotyping results inferredin silicofrom the WGS data were highly concordant (>99%) with laboratory typing performed in parallel. However, WGS was able to identify distinct nested clusters within groups of isolates that were otherwise indistinguishable using our current typing methods. Routine WGS was then used for prospective epidemiologic surveillance on a further 97L. monocytogenesisolates over a 12-month period, which provided a greater level of discrimination than that of conventional typing for inferring linkage to point source outbreaks. A risk-based alert system based on WGS similarity was used to inform epidemiologists required to act on the data. Our experience shows that WGS can be adopted for prospectiveL. monocytogenessurveillance and investigated for other pathogens relevant to public health.

scholarly journals Comparative Analysis of Subtyping Methods against a Whole-Genome-Sequencing Standard for Salmonella enterica Serotype Enteritidis

2014 ◽  
Vol 53 (1) ◽  
pp. 212-218 ◽  
Author(s):  
Xiangyu Deng ◽  
Nikki Shariat ◽  
Elizabeth M. Driebe ◽  
Chandler C. Roe ◽  
Beth Tolar ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Salmonella Enterica ◽  
Variable Number Tandem Repeat ◽  
The United States ◽  
Variable Number ◽  
Whole Genome ◽  
Molecular Subtyping ◽  
Content Type ◽  
Sporadic Cases

A retrospective investigation was performed to evaluate whole-genome sequencing as a benchmark for comparing molecular subtyping methods forSalmonella entericaserotype Enteritidis and survey the population structure of commonly encounteredS. entericaserotype Enteritidis outbreak isolates in the United States. A total of 52S. entericaserotype Enteritidis isolates representing 16 major outbreaks and three sporadic cases collected between 2001 and 2012 were sequenced and subjected to subtyping by four different methods: (i) whole-genome single-nucleotide-polymorphism typing (WGST), (ii) multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA), (iii) clustered regularly interspaced short palindromic repeats combined with multi-virulence-locus sequence typing (CRISPR-MVLST), and (iv) pulsed-field gel electrophoresis (PFGE). WGST resolved all outbreak clusters and provided useful robust phylogenetic inference results with high epidemiological correlation. While both MLVA and CRISPR-MVLST yielded higher discriminatory power than PFGE, MLVA outperformed the other methods in delineating outbreak clusters whereas CRISPR-MVLST showed the potential to trace major lineages and ecological origins ofS. entericaserotype Enteritidis. Our results suggested that whole-genome sequencing makes a viable platform for the evaluation and benchmarking of molecular subtyping methods.

scholarly journals Mixed Infections and Rifampin Heteroresistance among Mycobacterium tuberculosis Clinical Isolates

2015 ◽  
Vol 53 (7) ◽  
pp. 2138-2147 ◽  
Author(s):  
Chao Zheng ◽  
Song Li ◽  
Zhongyue Luo ◽  
Rui Pi ◽  
Honghu Sun ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Odds Ratio ◽  
Variable Number Tandem Repeat ◽  
Risk Groups ◽  
Variable Number ◽  
Mixed Infections ◽  
Proper Solution ◽  
Content Type ◽  
And Control ◽  
First Time

Mixed infections and heteroresistance ofMycobacterium tuberculosiscontribute to the difficulty of diagnosis, treatment, and control of tuberculosis. However, there is still no proper solution for these issues. This study aimed to investigate the potential relationship between mixed infections and heteroresistance and to determine the high-risk groups related to these factors. A total of 499 resistant and susceptible isolates were subjected to spoligotyping and 24-locus variable-number tandem repeat methods to analyze their genotypic lineages and the occurrence of mixed infections. Two hundred ninety-two randomly selected isolates were sequenced on theirrpoBgene to examine mutations and heteroresistance. The results showed that 12 patients had mixed infections, and the corresponding isolates belonged to Manu2 (n= 8), Beijing (n= 2), T (n= 1), and unknown (n= 1) lineages. Manu2 was found to be significantly associated with mixed infections (odds ratio, 47.72; confidence interval, 9.68 to 235.23;P< 0.01). Four isolates (1.37%) were confirmed to be heteroresistant, which was caused by mixed infections in three (75%) isolates; these belonged to Manu2. Additionally, 3.8% of the rifampin-resistant isolates showing no mutation in therpoBgene were significantly associated with mixed infections (χ2, 56.78;P< 0.01). This study revealed for the first time that Manu2 was the predominant group in the cases of mixed infections, and this might be the main reason for heteroresistance and a possible mechanism for isolates without any mutation in therpoBgene to become rifampin resistant. Further studies should focus on this lineage to clarify its relevance to mixed infections.

scholarly journals Compensatory Mutations of Rifampin Resistance Are Associated with Transmission of Multidrug-Resistant Mycobacterium tuberculosis Beijing Genotype Strains in China

2016 ◽  
Vol 60 (5) ◽  
pp. 2807-2812 ◽  
Author(s):  
Qin-jing Li ◽  
Wei-wei Jiao ◽  
Qing-qin Yin ◽  
Fang Xu ◽  
Jie-qiong Li ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Variable Number Tandem Repeat ◽  
Northern China ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Beijing Genotype ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Rifampin Resistance

ABSTRACTMycobacterium tuberculosiscan acquire resistance to rifampin (RIF) through mutations in therpoBgene. This is usually accompanied by a fitness cost, which, however, can be mitigated by secondary mutations in therpoAorrpoCgene. This study aimed to identifyrpoAandrpoCmutations in clinicalM. tuberculosisisolates in northern China in order to clarify their role in the transmission of drug-resistant tuberculosis (TB). The study collection included 332 RIF-resistant and 178 RIF-susceptible isolates. The majority of isolates belonged to the Beijing genotype (95.3%, 486/510 isolates), and no mutation was found inrpoAorrpoCof the non-Beijing genotype strains. Among the Beijing genotype strains, 27.8% (89/320) of RIF-resistant isolates harbored nonsynonymous mutations in therpoA(n= 6) orrpoC(n= 83) gene. The proportion ofrpoCmutations was significantly higher in new cases (P= 0.023) and in strains with therpoBS531L mutation (P< 0.001). In addition, multidrug-resistant (MDR) strains withrpoCmutations were significantly associated with 24-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat clustering (P= 0.016). In summary, we believe that these findings indirectly suggest an epistatic interaction of particular mutations related to RIF resistance and strain fitness and, consequently, the role of such mutations in the spread of MDRM. tuberculosisstrains.

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